ISSN:0306-0012    

DOI:10.1039/CS98312FX001

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

Chemical Society Reviews Vol 12 No 1 1983 Page Structure in Solvents and Solution-NMR and Vibrational Spectroscopic Studies By Martyn C. R. Symons NYHOLM LECTURE Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds of Various Orders By F. A. Cotton 35 Nitroso-alkenes and Nitroso-alkynes By T. I.. Gilchrist 53 Stereoselective Synthesis of Steroid Side-chains By J. Redpath and F. J. Zeelen 75 The Royal Society of ChemistryLondon

ISSN:0306-0012    

DOI:10.1039/CS98312BX003

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

NYHOLM LECTURE* Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds of Various Orders By F. Albert Cotton DEPARTMENT OF CHEMISTRY AND LABORATORY FOR MOLECULAR STRUCTURE AND BONDING, TEXAS A&M UNIVERSITY, COLLEGE STATION, TEXAS 77843, U.S.A. 1 Introduction Chemistry, to my mind, is the most beautifully balanced of all the sciences with respect to the roles of theory and experiment, or, in different terms, with respect to there being both abstract and concrete aspects to the phenomena we deal with. We can predict enough to make the subject intellectually satisfying and yet there is also much scope (indeed absolute necessity) for experimental observation. There is also a soul-satisfying aesthetic side to chemistry, as well as an enormous practical side, but I shall not digress in those directions. My lecture will focus on two aspects of the subject of multiple bonds between metal atoms’ in which the constructive interplay between theory and experiment has been lively and fruitful.At one point a theoretical result would give the experimental programme a nudge in the right direction while at another point an experimental result would elicit an appropriate theoretical effort. I shall be discussing, for the most part, triple and quadruple bonds between pairs of metal atoms, so I shall begin with the basic characteristics of these. They are formed primarily by the overlap of the d orbitals on the two metal atoms, as shown in Figure 1. How many of these five possible non-zero overlaps play a role, and what role they play in binding the metal atoms together depends on the number of electrons available and the number and types of ligands attached to the metal atoms.The simplest case is that of Mo, where there are no ligands and six electron pairs. In this case the overlap of two s orbitals must also be considered and we obtain a total of six bonding two-centre MO’s, all of which are occupied. A sextuple bond is thus formed, consisting of two non-degenerate 0,two degenerate A, and two degenerate 6 components. As a result of this highly multiple bonding Mo, has the shortest Mo-Mo distance known,2 193 pm, which may be compared * Delivered at University College, London, October 14, 1982 and also at Cambridge, Leicester, Edinburgh, Liverpool, and Bristol Universities and University College, Swansea in October, 1982.’ F. A. Cotton and R. A. Walton, ‘Multiple Bonds Between Metal Atoms,’ John Wiley and Sons, New York, 1982. * Y. M. Efremov, A. N. Samoilova, V. B. Kozhukhovsky, and L. V. Gurvich, J. Mol. Spectrosc., 1978, 73.430. 35 Synergic Interplay of Experiment and Theory in Studying Metal-Meta! Bonds i 77-adxz % c8dxv % Figure 1 The positive (bonding) CT,n, and 6 overlaps of d orbitals on a pair of metal atoms. There is a related set of negative (antibonding) overlaps (Reproduced by permission from Advanced Inorganic Chemistry, 4th Edn., by F. A. Cotton and G. Wilkinson, John Wiley & Sons, New York, 1980) to that in the metal, 276 pm. Calculations by either the SCF-Xcr-SW or Hartree- Fock-CI methods3 support (but considerably amplify) this simple bonding picture.In the case of Cr2 a similar qualitative bonding picture should obtain and in fact the internuclear distance4 in this molecule has the astonishing value of 168 pm [cf. 255pm in Cr(s)]. In this case, however, quantitative theory has yet to catch up with e~periment.~ When some electrons are removed from MoZ and ligands are added, several changes occur in the electronic structure. First, with increase in the oxidation number the role of the s orbitals becomes less important (actually, negligible for +2 and +3); second, there are fewer electrons; third, the ligands make some demand for the d orbitals to form metal-ligand bonds. In practice, two principal classes of compounds result, Figure 2: those based on a trigonal structure (a) and those based on a tetragonal structure (b). B.E. Bursten, F. A. Cotton, and M. B. Hall, J. Am. Chem. SOC., 1980, 102, 6348; P. M.Atha, I. H. Hillier, and M. F. Guest, Chem. Phys. Lett., 1980, 75, 84. D. L. Michalopoulos, M. E. Geusic, S. G. Hansen, D. E. Powers, and R. E. Smalley, J. Phys. Chem., 1982,86,3914. M. M. Goodgame and W. A. Goddard, J. Phys. Chem., 1981, 85, 215. Cotton Figure 2 The most common general structures for dinucfear compounds with M-M multiple bonds: (a) trigonaf, D3a;(b) tetragonaf, D,, In compounds with the trigonal structure we are usually dealing with M3+ atoms and the M-M bond order is 3.All of the 6 orbitals of the M, unit become involved in the M-L bonding and we are left only with the D and 7c overlaps for M-M bonding. Thus, we expect, on the simple d orbital overlap picture, to have a CJ bond and a n bond in which six electrons supplied by the metal atoms are used. Quantitative calculations by the SCF-Xa-SW method verify this and photoelectron spectra confirm the validity of the calculations." However, it is with the molecules or ions of tetragonal symmetry that we shall be chiefly concerned in this lecture. In this case, one of the two sets of 6 orbitals becomes primarily engaged in metal-ligand bonding, thus leaving 0, two TC, and the other 6 orbital available for M-M bonding. On the basis of simple overlap considerations, we expect the CJ bonding orbital to be very stable, the n bonding orbitals to be moderately stable and the 6 orbital to be the least strongly bonding.In the event the MZn+ unit concerned has a total of eight electrons, we have the qualitative picture shown in Figure 3. This simple d-orbital overlap picture does, in fact, embody the essence of the M-M bonding. If we look at the results of both Xct and Hartree-Fock calculations we see qualitative verification. The 6, n, and 0 orbitals do in fact lie highest, in that order, and have largely ( >70 o/o) d characters7 Two final points are to be noted in this introduction. First, the 6 and 6* orbitals are close in energy and the 6 -+ S* transition of an electron is orbitally allowed.This means that it is characteristic of all quadruply bonded systems to have such a transition in the visible region of the spectrum. Moreover, in nearly all cases, this allowed transition displays a progression in that totally symmetric vibrational frequency that is essentially vMM. A typical example is provided by Ref. 1, pages 382-389,415-417. 'Ref. 1, pages 356-364. Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds 0’ n* b‘ -0 Figure 3 A quulitutive picture of the M-M bonding orbitulsfor u tetrugonul M2X8 unit having eight electrons avuiluble for M-M bonding 3.0--2.0-w u Z a -m 0tn [I34 1.0 -17,000 18,000 -19,000 20,000 2 1,000 v -(cm-’) Figure 4 The 6 -+ 6* absorption band ofthe [M02Cl8l4-ion (Reproduced by permission from P.E. Fanwick, D. S. Martin, F. A. Cotton, and T. R. Webb, Inorg. Chem., 1977, 16, 2103) 38 Cotton Figure 5 A schematic representation of the basis for the uppeurunce of u progression in the vMM vibration in the 6 --* 6* excited state the [Mo2C1,I4- ion, Figure 4.The reason for the appearance of such a pro-gression is that the potential energy curve for the excited state is displaced along the dM-M co-ordinate, and thus transitions from the zero-ith vibrational level of the electronic ground-state strike several of the upper vibrational levels of the electronic excited-state, as shown in Figure 5. We shall later make use of this phenomenon. Finally, because of the fact that the 6 orbital is only weakly bonding and the 6* orbital is only weakly antibonding, a 027c4h2 quadruple bond is readily subjected to either electron loss or electron gain, as shown in Figure 6.Thus, an entire range of bond orders, 3.0, 3.5, 4.0, 3.5 and again 3.0 is accessible. 2 Bond Length uerw Bond Order: Not Always What One Expects It is one of the truisms of valence theory that the higher the bond order (other things being equal) the shorter the bond. Examples in support of this ‘rule’ are legion. There is, for example, the series from 02+to 022-in which there Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds a+ 33-0 3.0 3.5 4.0 3.5 3.0 BondOrders Figure 6 A schematic representation of how changes in the occupation of the 6 and 6* orbitals change the M-M bond order is a steady decrease of bond order as n* electrons are added, and the bond length increases from 112 pm to 149 pm.0-0 distancelpm Bond Order 02 + 112 2.5 02 121 2.0 02 -133 1.5 022-149 1.o Figure 7 The essential structural features of the [MO,(SO4)4Y-or [MO~(HPO,)~T-ions Cotton Relatively early in the study of M-M multiple bonds there emerged what seemed to be an equally satisfactory example of the same phenomenon in the following series of ions,' all of which are effectively isostructural (cf: Figure 7) in all other respects: Bond Electronic Lengthlpm Conjiguration Bond Order [Mo2 -211.1(1) a27r4d2 4.0 [MOz (S04)413-216.7(1) a27r46 3.5 [Mo2(HPO4),l2-222.3(2) 027r4 3.O Two further example^^.'^ from work in other laboratories are: Bond Electronic Lengthlpm Conjiguration Bond Order Ru~L~' 237.9(1) 02n4626*2n*2 2.0 [Ru2L2l+ 226.7(3) a27r4626*27r* 2.5 [Rh2(02CCH3)4(H20)2] 238.6(1) a27r462n*46*2 1.o [Rh2(02CCH3)4( H,O),] 23 1.6(2) a2n46271*~6* 1.5+ L = C22H22N,2- a tetradentate macrocycle Clearly, then, it was a simple matter to predict, confidently, that on oxidizing the [Tc2C1,I3- ion with a configuration of a27r4626*to [Tc2C1,I2- the bond length should decrease by 6-12 pm.The experimental results" are: Bond Lengthlpm Bond Order vTcTc/cm-[Tc2Cl8I3-210.5(1); 21 1.7(2) a27r4J26* 3.5 3 70 [Te2Cl8I2-215.1(1) a27r46' 4.0 307 There is no mistake in this tabulation: the species with the higher bond order has the longer bond.Moreover, this relationship is supported by the observed values of vTcTc. How do we explain this apparent contradiction of conventional wisdom? The explanation is based on two observations: (1) The o and n components of the quadruple bond are far more important in determining its total strength than the 6 component; hence even a small percentage change in the a and n bond strengths might be as important as a 50% change in the 6 bond strength. (2) In all these comparisons there are changes in the extent of ionization of the metal atoms accompanying the changes in the number of 6 or 6* electrons; as the effective positive charge on the metal atoms increases, there will be some contraction in the d orbitals and this will reduce the overlap in all components of the bond, including the strong a and 7r components.A. Bin0 and F. A. Cotton, Inorg. Chem., 1979, 18, 3562, and earlier references therein cited. L. F. Warren and V. L. Goedken, J. Chem. SOC.,Chem. Commun., 1978, 909. lo J. J. Ziolkowski, M. Moszner, and T. Glowiak, J. Chem. SOC., Chem. Commun., 1977, 760. F. A. Cotton, A. Davison, V. W. Day, M. F. Fredrich, C. Orvig, and R. Swanson, Inorg. Chem., 1982, 21, 1211. Synergic Interplay of’ Experiment and Theory in Studying Metal-Metal Bonds Let us return now to the first series, the set of dimolybdenum compounds, in which the bond order decreases from 4.0to 3.0. The formal state of ionization of the metal atoms also increases from +2 to +3.The increase in Mo-Mo bond length is the result of two factors, lower 6 bond order and decreased CJ and r overlaps, operating in the same direction. It is impossible, in the absence of some other source of information, to say how much of the total effect is due to each factor. Our earlier assumption that it could all be attributed to reduction in 6 bond order was (pardonably, we hope) naive and unjustified. The [Tc2C1813- to [Tc2Cl8l2-transformation differs from the preceding example in that the 6 bond order is increasing while the change in state of ionization is tending to decrease the strength of the 0and r components; the two factors are opposed in this case. The net increase of ca. 3.5pm in the Tc-Tc bond length would then imply that in this case the latter factor is more effective than the former in determining the bond length.If we look at other examples, we quickly see that there is no general rule as to which factor will predominate. In the Ru and Rh cases cited the two factors are opposed and each time the net effect shows the bond order change to be controlling. The rhodium example is not straightforward, however, because of near degeneracy of the 6* and r* orbitals and mixing of metal and ligand orbitals. In the Ru case, the bond order change is in the 7~ bonding, which is much stronger than 6 bonding and might thus have been expected to predominate. In the case of the following series of rhenium compounds’2 we have data that further illustrate the subtlety of the problem: Bond Electronic Lengthlpm Conjiguration Bond Order 1.Re2Cl,(PEt3), 222.2(3) 02n4d2 4.0 2. Re2C14(PEt3), 223.2(6) a2n4626*2 3.0 3. Re2C14(PMe2Ph), 224.1(1) ~~71~6~6~~3.0 4. [Re2C14(PMe2Ph)4]+ 221.8(1) 02n4h26* 3.5 5. [Re2 C14(PMe2 Ph),I2 22 1.5(2) o2n46 4.0 +Comparison of 2 and 3 indicates that differences of the order of 1 pm can arise from minor variations having nothing to do with changes in oxidation state or bond order. Several years ago, from a comparison of I and 2, it appeared that for the di-rhenium compounds the change from bond order 4 to 3 (which should increase the distance) accompanied by a decrease in ionization state of the metal atoms from +3 to +2 (which might decrease it) approximately offset each other. However, the change in composition, which could have a significant effect on internal repulsions, made this a less than ideal case.We now have the results for compounds 3-5 in which composition is unchanged, and we also alter the electron configuration one step at a time. Here we see again (from the 5 to 4 comparison) an insensitivity of the Re-Re l2 F. A. Cotton, K. R. Dunbar, L. R. Falvello, M. Tomas, and R. A. Walton, in course of publication. Cotton distance to addition of the first 6* electron. The addition of the second one, however, causes an increase of 2.3(l)pm, indicating that here the bond order effect is, by a slight amount, dominant. In all the foregoing work, changes in bond order have been inextricably coupled with changes in the total number of electrons and, hence, with the charges on the metal atoms.It would obviously be desirable to have a way of changing the bond order without adding to or subtracting from the total electronic population, with the attendant charge effects. There are, in fact, two ways in which the influence of 6 bond order of M-M distance can be observed independently of charge effects. One depends on reduc- tion of the 6 bond order by internal rotation from the eclipsed towards the staggered conformation. The second depends on estimating bond lengths in electronically excited states. A. Internal Rotation.-Let us consider an eclipsed species. As the angle of internal rotation, x, changes from 0" (eclipsed conformation) to 45" (fully staggered conformation) the 6-6 overlap changes from its maximum value to zero according to the function cos 2x.l Since X * * * X repulsive forces would lessen with increasing x, since the 6 bond strength need not be strictly proportional to overlap, and since bond length need not be strictly proportional to bond strength, a strictly linear relationship between dMM and cos2x cannot necessarily be expected, but one might expect a relationship approximating to this. Of course, the biggest problem is that the observation of dMM as is changed in an otherwise invariant species X4M ZMX, is not experimentally possible. There is, however, a feasible experimental approach that provides nearly the same information.We examine the structures of several M2X4( LL)2 molecules in which the steric properties of the bridging bidentate ligand, LL, serve to change the torsion angle while keeping M, X, and the ligating atoms of L invariant, or virtually so.Mo,Cl,(dmpe), , Figure 8, is an e~amp1e.l~ Thus far, for the M024+ unit, three suitable systems have been found and studied. The results are presented in Figure 9, where it is seen that there is an essentially linear experimental relationship between d(Mo-Mo) and cos 2x. The phosphine ligands differ somewhat in basicity (and one contains As and P rather than two P atoms) but control experiments suggest that these changes alone have little effect on d(Mo-Mo). It is also known that in general d(Mo-Mo) is not sensitive to a change from C1 to Br in M2X8"- species.The total change in Mo-Mo distance (extrapolated) as x goes from 0" to 45" is 6.4pm. This should probably be regarded only as a lower limit on the change resulting from loss of the 6 bond since the bridging diphosphine ligands probably tend to hold the metal atoms together. l3 F. A, Cotton, P. E. Fanwick, J. W. Fitch, H. D. Glicksrnan, and R. A. Walton, J. Am. Chem. SOC., 1979, 100, 1752. l4 F. A. Cotton and G. L. Powell, lnorg. Chem., in press. Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds Figure 8 The structure of the Mo,C1,(Me,PCHzCH2PMe2), molecule 2.195 2.185 h O5 a, 0 c 2.175 b t UJ_-n 2.165-0 c 0 m 0 2.155 2 I 0 2 2.145 2.135 I ,I 0 0.25 0.5 0.75 1.0 cos 2x Figure 9 Mo-Mo bond distance vs.COS~X,where x is the torsion angle. dmpe = Me2PCH2CH2PMe2;arphos = Ph,AsCH,CH,PPh, ;dppm = Ph2PCH2PPh2 Cottoll B. Electronic Excitation.-The excitation of an electron from the 6 to the 6* orbital has an effect formally equivalent to diminishing the S bond order by one unit. For the ground state of the system the M-M bond length is known by direct X-ray crystallographic measurement. For the excited states the expected increase can be estimated from the Franck-Condon factors when a progression in vM-M is observed, as it usually is for the 6 --+ 6* transitions. Several such estimates have been made :' Mo2(02CMe), ll(1)pm [MOz C1gl4 -1w 1Pm [Re2C1gIZ-7mPm [Re2C1,(PPr,),]+ 6.5(5)pm These magnitudes are consistent with the observations already discussed.However, the paucity of data of all kinds still leaves the subject in a quanti- tatively unsatisfactory state. 3 Why do Tungsten-to-tungsten Quadruple Bonds Differ so Greatly from those of Molybdenum? From the initial discovery that Mo(CO), reacts with acetic acid and other carboxylic acids to give products of composition Mo(O,CR), (and even before the true nature of these compounds was recognized) attempts to prepare homologous compounds of tungsten by similar methods have been unavailing. With respect to the reaction just mentioned, we now know that for both Mo(CO), and W(CO), the major product is the same, as shown in equations (1) and (2).l6,I7 The reaction with W(CO), simply fails to produce any W" product.___+w(co)6 + excess RC02H 100% [W,02(02CR)6(H,0)3]Z+ (2) The trinuclear species contain equilateral-triangular clusters with M-M single bonds and are quite interesting in their own right. Gradually, over the past twenty years, methods have been found to prepare compounds with W-W quadruple bonds, and analogues of nearly all the principal types known for molybdenum have been made and studied. Almost always, the tungsten compounds are less stable and more reactive than their molybdenum analogues. The carboxylates themselves have been made by the following reactions: (3; R = CF3,'' or Ph"): Is I am indebted to Professor P. E. Fanwick of the University of Kentucky for these estimates.l6 A. Bino, F. A. Cotton, Z. Dori, S. Koch, H. Kiippers, M. Millar, and J. C. Sekutowski, Inorg. Chem., 1978, 17, 3245. A. Bino, F. A. Cotton, and Z. Dori, J. Am. Chem. Soc., 1981, 103, 243. A. P. Sattelberger, K. W. McLaughlin, and J. C. Huffman, .I.Am. Chem. So(..,1981, 103, 2880. l9 F. A. Cotton and W. Wan& Inorg. Chem., 1982, 21, 3859. 45 Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds Recently, even a compound containing the [W2C18]4- ion has been isolated and structurally characterized (equation 4)20 In contrast to the relative instability and inaccessibility of the quadruply bonded di-tungsten compounds, there is a great variety of triply bonded W,X6 compounds that are as easily made and as stable as their molybdenum analogues,' e.g.7 W2(NMe2)6 * Before searching for an explanation of these curious homologies and dis- homologies, we may note that for both triple and quadruple bonds, the W-W distances are systematically about 10-12 pm greater than the Mo-Mo distances when molecules of the same stoicheiometry are compared.Our first step towards an explanation was the recognition that while the ordinary bond radii of Mo and W are approximately equal (with that of W actually being a few pm smaller !) the two atoms should behave quite differently at the extremely short internuclear distances found in the triple and quadruple bonds. This would be expected because of the markedly denser core of the W atom.2' At distances in the range of 205-235pm core-core repulsions should be far more important between a pair of tungsten atoms than between a pair of molybdenum atoms.It is for this reason that for both triple and quadruple bonds, the W-W distances are 10-12pm greater than Mo-Mo distances. In the case of the triple bonds, where only CT and 7c overlaps contribute to the bonding, an increase of ca. 10pm has only a minor effect on the strength or reactivity of the bond. This is because the magnitude of and 7c overlaps is not strongly distance-sensitive in the range we are dealing with. For the 6 bond, however, the strength and the stability of the electrons might be expected to show considerable sensitivity to a 10 pm change in distance, when the qualitative character of the 6-6 overlap is considered.This qualitative idea has been tested quantitatively by SCF-Xa-SW calculations and by photoelectron spectroscopy, as will now be explained. With the aid of calculations we can assign the measured photoelectron spectra (PES) of Mo~C~~(PH~)~ and its W analogue.23 We chose these particular substances because they are the simplest type of compound formed by both Mo and W that are sufficiently stable and volatile to allow measurement of the PES. Figure 10 shows the He1 spectra of the Mo and W compounds. These spectra confirm our qualitative idea that while the electronic structures of quadruply bonded M024+ and W24.t compounds are overall very similar, there is a significant -indeed crucial -difference in the stability of the 6 bonding 2o F.A. Cotton, G. N. Mott, R. R. Schrock, and L. G. Sturgeoff, J. Am. Chem. SOC., 1982, 104, 6781. 21 M. H. Chisholm and F. A. Cotton, Acc. Chem. Rex, 1978, 11, 356. 22 Ref. 1, page 350. 23 F. A. Cotton, J. L. Hubbard, D. L. Lichtenberger, and I. Shim, J. Am. Chem. SOC., 1982, 104, 679. Cotton ionization energy (eV1 17 15 13 11 9 7 1 I 1 Ju1 Y C :: I I I I 1 1 I 5 7 9 11 13 15 electron kinetic energy (eV) Figure 10 The He1 photoelectron spectra ~J'Mo,CI,(PM~,),(A) and W,CI,(PMeJ), (B) (Reproduced by permission from Ref. 23) electrons. Armed with this result, we can now discuss and explain the chemical differences between the molybdenum and tungsten compounds.In general, the W2'+ compounds tend to be more reactive because of the higher energy of the electrons in the HOMO -the 6-bonding orbital. This could account for reactivity of many kinds being more rapid for the tungsten compounds. We shall examine one mode of reaction that seems to be especially important, oxidative addition, as represented schematically in equation (5). Actually, a few oxidative addition reactions are known to occur with MoZ4+ compounds, but they are favoured only under strenuous conditions and are generally reversible. Thus, the preparation of [Mo2C1,I4-from Mo2(02CMe), Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds CI Figure 11 The structure of the [MozC1,HI3-ion resulting from oxidative addition of HCI (or Hf ) to [Mo,CI,]~-at higher temperatures is carried out in 12 M-HCl at about 0 "C.If the temperature is raised to about 60°C one obtains instead the [Mo,CI,H]~- ion,24 which can be considered to arise by oxidative addition of HC1 to [MO~C~,]~- followed by loss of C1-or simply by protonation of the 6 bond [i.e., it is a product of type (c) in the above equation]. The structure of this hydrido-bridged anion is shown in Figure 11. This ion undergoes many of the same reactions as the [Mo2Ci,l4- ion because C Figure 12 The structure of the W,Cl,(PBu,"),(O,CPh)~(p-H)(p-CI)molecule 24 A. Bino, B. E. Bursten, F. A. Cotton, and A. Fang, Inorg. Chem., 1982, 21, 3155, and earlier references therein cited. Cotton reversal of the protonation or oxidative addition reaction readily occurs.' With tungsten compounds the oxidative addition occurs even under very mild acidic conditions and generally appears to continue through further irre- versible steps leading to end products in higher oxidation states, such as the [W302(02CMe)6(H20)3]2clusters obtained when W(CO)6 reacts with acetic + acid.Direct proof for an initial oxidative addition has thus far been lacking.26 Recently we were fortunate enough to find a system in which the product of oxidative addition can be intercepted and structurally characterized. Several years ago, San Filippo and co-workers demonstrated2' that Mo2X,(PR3), compounds react with benzoic acid to afford Mo~X~(PR~)~(O~CP~)~ species, Ph Ph of the type shown in (1).On attempting the same reaction with W,Cl,(PBu",), we obtained instead the oxidative addition product resulting, presumably, from reaction of the initially formed W2C12(PB~"3)2(02CPh)2with the HC1 generated.28 The structure of this molecule is shown in Figure 12.The bridging hydrogen atom was found and refined (actually twice, since there are two independent molecules in the crystal), but lest there be those who doubt the reliability of such a result, the n.m.r. evidence summarized in Figure 13 un- equivocally supports its presence. To close, I should like to tell you of some recent observations by Malcolm Chisholm and his co-workersZ9 that beautifully complement those just discussed. The proposition that W-W quadruple bonds far more readily undergo oxidative addition than their Mo-Mo analogues implies the following 'conjugate' proposition: Mo-Mo triple bonds will far more readily undergo reductive elimination (to generate quadruple bonds) than their W -W analogues.Chisholm has reported reactions (6)-(9) that fully support this proposition. 25 J. San Filippo, Jr., H. J. Sniadoch, and R. L. Grayson, Znorg. Chem., 1974, 13, 2121. 26 Sattelberger and co-workers (ref. 18) have reported observations leading them to the tentative conclusion that reaction of W,(O,CCF,)., with aqueous HCI at -10°C may give [W2Cl8HI3- in addition to [W2Cl9I3 -. 27 J. San Filippo, Jr. and H. J. Sniadoch, Znorg. Chern., 1976, 15, 2209; J. A. Potenza, R. J. Johnson, and J.San Filippo, Jr., ibid., 1976, 15, 2215.'* F. A. Cotton and G. N. Mott, J. Am. Ckem. Soc., 1982, 104. 5978. 29 M. J. Chetcuti, M. H. Chisholm, K. Folting J. C. Huffman, and J. Janos, J. Am. Chem. SOC., 1982,104, 4684. 49 Synergic Interplay of Experiment and Theory in Studying Metal-Metal Bonds but NMe I N (PhCH2)(Me2N)2h40~Mo(NMe2)2(CH2Ph) +PhN4 ‘NPh (excvss) H Mo2(PhNNNPh )4+PhCH2CH2Ph (8) but N (PhCH2) (Me2N)2WsW( NMe22)(CH2Ph) +PhNd ‘NPh (excess) H (9) NMe2) +2Me2NH(PhCHZ) ( ’N‘PhN-NPh II Me2N)W=W(CH2Ph) ( PhNu NPh ‘N’ Cotton 50 a 8(H) = 1.92 vs. TMS NPC)= 12.0 1 vs.H,PO,B(P') -8.0 Figure 13 A diagrammatic summary of the n.m.r. euidence for the presence of the p-H atom in W2C12(PBu",)2(02CC6H,),.Coupling constants are given in Hz (For details see Ref: 28) Acknowledgements. The long and faithful support of the U.S. National Science Foundation has been vital to the success of our research in this field. I have also been extremely fortunate to enjoy the friendship and professional collabora- tion of many excellent chemists, especially Professor M. H. Chisholm of Indiana University and Professor R. A. Walton of Purdue University throughout many of the developments in this field of chemistry.

ISSN:0306-0012    

DOI:10.1039/CS9831200035

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

Nitroso-alkenes and Nitroso-alkynes By T. L. Gilchrist ROBERT ROBINSON LABORATORIES, UNIVERSITY OF LIVERPOOL, P.O. BOX 147, LIVERPOOL L69 3BX 1 Introduction The nitroso group has been recognized for many years as a powerful activating group for nucleophilic substitution in benzenoid aromatics,’ but much of the chemistry of other types of conjugated nitroso compounds has been discovered only recently. Nitroso-carbonyl compounds (RCONO) have been generated and have been shown to participate, through the nitroso group, in Diels-Alder and ene reactions.2 Nitrosyl cyanide2 and C-nitroso-imines [RIN =C(R’)N0I3 are also excellent dienophiles. This review deals with the chemistry of two other classes of conjugated nitroso compounds, in which the nitroso group is attached to a carbon-carbon double bond, (1) or triple bond, (2). R’ R---NO R2+(:(1) (2) Only a few compounds of type (1) have been isolated. The first such compound (1; R’ = R2 = R3 = F) was reported in 19604and since then a few others, usually with bulky alkyl or halo substituents at the /?-carbon atom, have been described.There is, however, substantial evidence for the existence of a wide range of vinyl- nitroso compounds in solution as transient intermediates. Some of these inter- mediates have been detected spectroscopically, or simply by the appearance of a characteristic blue colour in the solution. This group contains many /?-alkyl- and 8-aryl-substituted compounds, some halo-substituted derivatives, and a few with 8-alkoxy or /?-diakylamino substituents.Lifetimes of these compounds vary from many weeks at room temperature to short periods at low temperatures. Other types of vinyl-nitroso intermediates have not been detected directly, and the evidence for their existence is based on trapping experiments: for example, all the known intermediates H,C=C(R)NO are in this category. Representative examples of these different groups of vinyl-nitroso compounds, for which there is good direct or indirect evidence, are shown in Table 1. 3. Miller and A. J. Parker, Awst. J. Chem., 1958, 11, 302. G. W. Kirby, Chem. SOC.Reti., 1977, 6,1. T. L. Gilchrist, C. J. Harris, F. D. King, M. E. Peek, and C. W. Rees. J. Chem. SOC.,Prrkrn Trum I. 1976, 2161. C. E. Griffin and R.N. Haszeldine, J. Chem. SOC., 1960, 1398. 53 Nitroso-alkenes and Nitroso-alkynes Table 1 Representative nitroso-alkenes (1) R2 R3 Properties Ref: F F Blue gas, stable up to 100°C 4 C6H2Me,-2,4,6 Me Blue solid, m.p. 47-58 "C 5 CMe, H Blue solid, m.p. 38°C 6 c1 Me Isolable at r.t. 7 -(CH2)4-Blue solid at -5O"C, 8 decomp. above -30 "C c1 H 7 c1 c1 } Long-lived in solution 7 Ph Me Detected in solution by 9 morpholino COMe ] colour 10 H Ph Kinetic evidence for its 11,12 existence; also cycloaddition reactions H H 13COMe t Detected only by 14H HI cycloaddition reactions c1 7 * Stereochemistry about the double bond has not been established These compounds are potentially very useful synthetic intermediates because of the presence of a double bond in conjugation with the nitroso group; there is an obvious relationship between them and other types of activated alkenes.Thus, the /?-carbon atom is expected to be highly electrophilic, and indeed reactions with nucleophiles are the best-known features of their chemistry. In the following sections of this review, the methods of generation and characteristic physical properties of vinyl-nitroso compounds are described, and the known chemistry is then categorized according to the types of reaction involved. The final section deals with nitroso-alkynes, about which very little has so far been published, there being good evidence for the existence of only two such compounds (2; R = Bun or Bu') at low temperatures in solution.15 2 Methods of Generation of Nitroso-alkenes A.By 1,CElirnination Reactions of a-Halo-oximes, and Related Methods.-The reaction of a-halo-oximes with bases (Scheme 1) is by far the most important method for the generation of vinyl-nitroso compounds. A Scheme I Gilchrisr The method has, for example, been used to generate all the compounds in Table 1, with the exception of (la). Chloride is the most common leaving group, but other halides have also been used. Since the vinyl-nitroso compounds are very susceptible to nucleophilic attack (Section 3B) the choice of reaction conditions is important. The reaction must be carried out with poorly nucleophilic solvents and bases unless these are also to be used as nucleophiles to intercept the nitroso- alkene.For the long-lived species, the tertiary amines triethylamine5 and 1,5-diazabicyclo[4.3.0]non-5-ene6have been used. Transient species are best generated from the halo-oxime in a non-nucleophilic organic solvent by means of an insoluble inorganic base such as sodium carbonate9.' or calcium hydroxide.* This allows the intermediates to be generated slowly and minimizes side reactions involving more than one molecule of the nitroso intermediates. There are three general methods for the preparation of the required halo- oximes. The first is the reaction of the appropriate haloketone with hydroxyl-amine. Chloro-oximes are thus normally prepared from chloroketones and hydroxylamine hydrochloride in alcoholic solution.For bromo-oximes, hydroxyl- amine sulphate can be used to avoid halide exchange which can occur with the hydrochloride. l6 Alcoholic solvents can also interfere, as nucleophiles to displace the halide, if reaction times are pr01onged.l~ A second method, used for some chloro-oximes, is the reaction of nitro-alkenes with metal chlorides such as tin(n) chloride" or titanium(1v) chloride.' The third method, which is also limited to chloro-oximes, is the addition of nitrosyl chloride to alkenes." This reaction was first introduced over a century ago by Tilden and Shenstone" as a method of preparing crystalline derivatives of terpenes. More recently, the reaction has been extended to a wide range of nucleophilic and electrophilic alkenes, mainly by Ogloblin and his co-workers in the U.S.S.R. This is the method of choice for the preparation of a-chloro-oximes of cyclic ketones20,2 and of many other alkyl ketones.22 It is also a valuable route to chloro-oximes CTCH,C(R)NOH where W.Hobold, U. Prietz, and W. Pritzkow, J. Prakt. Chem., 1969, 311, 260. K. Wieser and A. Berndt, Angew. Chem., Int. Ed. Engl., 1975, 14, 70. E. Francotte, R. Merenyi, V. Vandenbulcke-Coyette, and H. G. Viehe, H~L?.Chim. Actu, 1981.64. 1208. P. Ciattoni and L. Rivolta, Chim. Znd. (Milan), 1967, 49, 1186. A. Dornow and H. D. Jordan, Chem. Ber., 1961, 94, 76. lo P. Bravo and C. Ticozzi, Gazz. Chim. ltal., 1975, 105, 91. J. H. Smith, J. H. Heidema, and E. T. Kaiser, J. Am. Chrm. SOC., 1972, 94, 9276. l2 D.E. Davies, T. L. Gilchrist, and T. G. Roberts, J. Chem. Soc., Perkins Trans. I, 1983. in press, R. Faragher and T. L. Gilchrist, J. Chem. SOC.,Prrkin Trans. I, 1979, 249. l4 T. L. Gilchrist and T. G. Roberts, J. Chem. Soc., Perkin Trans. I, 1983, in press. Is E. Robson, J. M. Tedder, and D. J. Woodcock, J. Chem. Soc., (C). 1968, 1324. l6 P. Blumbergs, C. B. Thanawalla, A. B. Ash, C. N. Lieske, and G. M. Steinberg. J. Ory. Chrm.. 1971,36, 2023. A. Dornow, H. D. Jordan, and A. Muller, Chem. Ber., 1961, 94, 67. Is L. J. Beckham, W. A. Fessler, and M. A. Kise, Chbm. Rec., 1951, 48, 319; P. P. Kadzyauskas and N. S. Zefirov, Russ. Chem. Reo., 1968. 37, 543. l9 W. A. Tilden and W. A. Shenstone, J. Chem. SOC., 1877, 31, 554. 2o M. Ohno, N. Naruse, and I.Terasawa, Org. Synth., Coll. Vol. V, 1973, 266. M. Ohno, N. Naruse, S. Torimitsu, and M. Okamoto, Bull. Chem. SOC. Jpn., 1966, 39, 1119. 22 M. Angermann, J. Beger, G. Collin, A. Ebenroth, R. Hellmig, H. Lunkwitz, P. Pabst, U. Prietz. W. Pritzkow, H. Schaefer, R. Siedler, and R. Weller, Wiss. 2. tech. Hochschulr Chrm. Lruna-Merseburg, 1966, 8, 187. Nitroso-alkenes and Nitroso-alkynes R = CHO, COMe, COPh, and CN.23The reaction of alkenes with nitrosyl chloride is not always a simple one:” the major primary product is usually the B-chloro-nitroso compound which may dimerize, or rearrange to the chloro- oxime if the alkene bears an a-hydrogen (Scheme 2). + NOClx Scheme 2 The primary adduct (3) is normally that predicted by the Markovnikov rule, and the reaction with simple alkenes is classed as an electrophilic addition.18 The surprisingly rapid addition of nitrosyl chloride to some a/?-unsaturated carbonyl compounds23 could be the result of the prior co-ordination of the nitrosyl cation to the carbonyl oxygen.The nitrosochloride dimers (4)have also been used as the precursors of some vinyl-nitroso comp~unds,~~~~~- 26 and there is good evidence that the reactions of some dimers (4)and of the corresponding chloro-oximes (5) with nucleophilic bases go through common intermediate^.^^.^^.^^ Exceptionally, the nitroso- chloride dimers (6) derived from styrenes react with tri-n-butylamine to give orange dimers (7) of the p-nitros~styrenes.~~ A-H C1 n-H-l3 K. A. Ogloblin and A.A. Potekhin, J. Gen. Chem. USSR, 1964, 34, 2710; K. A. Ogloblin and A. A. Potekhin, J. Org. Chem. USSR, 1965, 1, 1370; K. A. Ogloblin and V. P. Semenov, J. Org. Chem. USSR, 1965, 1, 1378. 24 R. U. Lemieux, T. L. Nagabhushan, and I. K. ONeill, Tetrahedron Lett., 1964, 1909. ”W. Pritzkow, H. Schaefer, P. Pabst, A. Ebenroth, and J. Beger, J. Prakt. Chem., 1965, 29, 123. 26 P. Bravo, G. Gaudiano, C. Ticozzi, and A. Umani-Ronchi, Gazz. Chim. Ital., 1969, 99, 549.’’0.Wallach, Liebigs Ann. Chem., 1899, 306,278. 56 Gilchrist There are a few examples of the use of oximes bearing leaving groups other than halides for the generation of vinyl-nitroso compounds. Nitrosyl hydrogen- sulphate, NOS03H, has been added to alkenes and the adducts used as sources of vinyl-nitroso compounds." Nitrite has also been used as a leaving group.6 The ring opening of oximes of a-epo~yketones~~ (Scheme 3) provides an interesting NO "OHbo bOLi--L -a"' OH Reagent: i, Me,CuLi, Et,O, -25 "C Scheme 3 variant of this approach.Simple dehydration of a-hydroxyketoximes does not appear to have been used as a route to these intermediates, but the acid-catalysed dehydration of the sulphoxide (8) is postulated to involve the nitroso-alkene (9).30 MeS MeS B. By Combination of Nitric Oxide with Vinyl Radicals.-Nitrosotrifluoroethylene (la) was formed by the sensitized photolysis of iodotrifluoroethylene in the presence of nitric ~xide.~ It is probable that the product is formed by the combination of trifluorovinyl radicals with nitric oxide.This is the only vinyl- nitroso compound which has so far been detected directly in this type of reaction, but others have been postulated as reaction intermediates. Thus, ethyne reacts with hydrogen atoms and nitric oxide to give HCN and formaldehyde, which, it is suggested, are formed by the rearrangement and fragmentation of nitroso- ethylene (Scheme 4).31 Several similar reactions have been rep~rted;~'.~' for example, the sequence shown in Scheme 5.32 0-NHx;o-.* +H2CO + HCN H HH Scheme 4 W. Kisan and W. Pritzkow, J. Prakt. Chem., 1978, 320, 59. 29 E. J. Corey, L. S. Melvin, and M. F. Haslanger, Tetrahedron Lett., 1975, 3117. 30 H. G. Corkins, L. Storace, and E. R.Osgood, Tetrahedron Lett., 1980, 2025.31 A. G. Sherwood and H. E. Gunning, J. Am. Chem. SOC., 1963, 85, 3506. 32 J.-M. Surzur, C. Dupuy, M.P.Bertrand, and R. Nouguier, J. Org. Chem., 1972, 37, 2782. Nitroso-alkenes and Nitroso-alkynes Reagent: i, NO HCN + Go Scheme 5 C. Other Methods.-Other methods are so far restricted to examples with special structural features, and the evidence for the formation of vinyl-nitroso inter- mediates is in all cases indirect, being based on the nature of the final products. Abramovitch and his co-workers have shown that 2-azidopyridine 1-oxides decompose when irradiated or when heated above about 85 0C.33934If a 3-substituent is present, two types of product can be isolated: the 6H-1,2-oxazines (10) and the 2H-pyrrole 1-oxides (1 1).These may undergo further transforma- tions in the presence of a nucleophilic solvent or if there is no 3-substituent. It is suggested that the azides undergo a fragmentation to dienyl-nitroso intermediates which then cyclize (Scheme 6). The oxazines (10) are the kinetic Rm;+aR-pcN-&;N3 NO “/O I I 0-(10) 0-(11) Scheme 6 products and the nitrones (11) the thermodynamic products. Similar fragmenta- tions have been observed with the azidopyrazine l-oxide (12)33 and with the azidoquinoxaline 1,4-dioxide (13).35 0-33 R. A. Abramovitch and B. W. Cue, J. Am. Chem. SOC., 1976, 98, 1478. 34 R. A. Abramovitch, 1. Shinkai, B. W. Cue, F. A. Ragan, and J. L. Atwood, J. Heterocycl. Chem., 1976, 13, 415; R.A. Abramovitch and C. Dupuy, J. Chem. SOC., Chem. Commun., 1981, 36. 35 J. P. Dirlam, B. W. Cue, and K. J. Gombatz, J. Org. Chem.. 1978, 43,76. Gilchrist Other ring-cleavage reactions in which vinyl-nitroso compounds are postulated as intermediates are illustrated in Schemes 7,36 8,37 and 9.38 That shown in Scheme 9 can be regarded as a retro-Diels-Alder reaction which is facilitated by the production of an aromatic fragment (the indole). ABr X+X ANG;, NO Scheme 7 Scheme 8 Scheme 9 The nucleophilic addition-elimination reactions of sulphur ylides with nitrile oxides probably also produce nitroso-alkenes as intermediates, but these then react further with the nucleophilic ylides to give 2:l addu~ts.~~?~~?~'An example is shown in Scheme 10.3h S. Ranganathan, B. B. Singh, and C. S. Panda, Tetrahedron, 1977, 33, 2415. 37 A. Silveira and S. K. Satra, J. Org. Chem., 1979, 44, 873. 38 D. E. Davies and T. L. Gilchrist,.J. Chern. SOC.,Perkit Trans. I, 1983, in press. 39 P. Bravo, G. Gaudiano, and A. Umani-Ronchi, Gazz. Chim. ItaI., 1967, 97, 1664; Y. Hayashi, T. Watanabe, and R. Oda, Tetruhedron Lett., 1970, 605; R. Faragher and T. L. Gilchrist, J. Chem. SOC., Perkin Trans. 1, 1977, 1196. 40 P. Bravo, G. Gaudiano. P. P. Ponti, and C. Ticozzi, Tetrahedron, 1972, 28, 3845. -> Nitroso-alkenes and Nitroso-alkynes -i +-CH2-SOMe2 + PhC-N-0 Reagent: i, CH,iOMe, Scheme 10 3 Structure and Physical Properties No X-ray or microwave structure determinations have so far been carried out on the isolable nitroso-alkenes.Molecular orbital calculations, using the Hii~kel~~ and c7ND04' methods, have been carried out on nitrosoethylene, and ab initio (STO-3G) calculations have been reported for 2-and 3-nitro~ofuran.~~ For nitrosoethylene the transoid structure (14) is calculated to be of slightly lower energy than the cisoid (15).41 In the nitrosofurans the planar structures are calculated to be much more stable than forms with the nitroso groups out of the plane, the barriers to rotation being high (29-36 kJ mole- 1).42 The spectroscopic properties of the long-lived vinyl-nitroso compounds have been tabulated by Viehe et al.7 The blue colour is due to a n -+ II*absorption band (Ama 675-795 nm) with a small extinction coefficient (E 20-60).A higher energy absorption band is also observed (sometimes showing two maxima) in the 250-350nm region; this may be due to an excitation involving considerable transfer of charge to the nitroso group.41 Infra-red spectra normally show two bands in the region 1420--1660cm-', a region in which the N=O stretching frequencies of other monomeric nitroso compounds lie.43 An absorption at 1485cm-' (CCl,) for the di-t-butyl compound (lc) is assigned as the N=O stretching band,6 and the absorption in the 1420--148Ocm-' region of other vinyl-nitroso compounds has also been assigned as the N=O stretching band, the higher frequency band (1500-1660 cm-') being the C=C stretching absorp- ti~n.~In the 'H n.m.r.spectra, the /%hydrogen atoms of compounds (lb) and (le) are deshielded and appear respectively at 6 9.135 and 8.68.* The a-hydrogen atom in compound (lc) appears at much higher field (6 6.30).6 41 V. Bhujle, U.P. Wild, H. Baumann, and G. Wagniere, Tetrahedron, 1976, 32, 467. 42 I. G. John and L. Radom, J. Am. Chem. SOC., 1978, 100, 3981. 43 C. N. R. Rao and K. R. Bhaskar, in 'The Chemistry of the Nitro and Nitroso Groups' Part 1, ed. H. Feuer, Interscience, New York, 1969, p. 137. 60 Gilchrist The limited physical data are consistent with structures for vinyl-nitroso compounds in which there is strong conjugative interaction between the carbon- carbon double bonds and the nitroso groups. 4 Reactions A. Unimolecular Reactions.-Two types of intramolecular rearrangement have already been referred to: cyclization to oxazetes (Schemes 4 and 5), and the cyclization of dienyl-nitroso compounds to 6H- 1,2-oxazines (Scheme 6).Oxazetes have also been isolated from the thermal rearrangement of the nitroso- alkene (1~)~(Scheme 11) and from the reaction of the bromo-oxime (16) with base, in which the vinyl-nitroso compound (9) is proposed as an intermediate30 (Scheme 12). Viehe and his co-workers have suggested that this is the major Me ?C Reaction conditions: i, 220°C; ii, 240°C Scheme 11 MeS O-N MeSw::y3-MeS Br MeS (16) Reagent: i, DBN Scheme 12 decomposition pathway of many other nitroso-alkenes in the absence of added nucleophiles, and they cite the additional examples of the formation of benzonitrile from the oxime (17), and of benzophenone from the oxime (18), when these oximes are treated with sodium hydrogen carbonate in dichloromethane.' c1 (17) Another possible mode of rearrangement of appropriately substituted vinyl- nitroso compounds is a [1,5] hydrogen shift.An example is provided by the rearrangement of 2-methyl- l-nitrosocyclohexene (19) (Scheme 13). The presence of the nitroso-alkene in solution is revealed by a blue colour which disappears within 30 min, and the unsaturated oxime (20) can be isolated from the solution.28 61 Nitroso-alkenes and Nitroso-alkynes Scheme 13 This is a major mode of decomposition of other nitroso-alkenes bearing two @-alkyl substituents,22 the unsaturated oximes being isolated in fair yields (28-72 %).A similar unsaturated oxime is isolated when the chloro-oxime (21) is treated with sodium ~arbonate.~ c1 B. Reactions with Nucleophi1es.-Conjugate addition of nucleophiles to vinyl- nitroso compounds takes place as shown in Scheme 14. Thus, when halo-oximes are used as the precursors, the overall reaction with nucleophiles is displacement Scheme 14 of the halide anion by the nucleophile. It is likely that many reactions of halo-oximes with weakly basic nucleophiles such as cyanide44 or phosphine~'~,~~ do involve a direct displacement of the halide, but with more strongly basic nucleo- philes, or in the presence of an external base, an elimination-addition mechanism is preferred.There is good evidence that nitrosochloride dimers derived from alkenes also react with nucleophilic bases by an elimination-addition mechanism. These compounds react faster with sodium methoxide than with piperidine, but in the presence of both bases, the major products are the piperidino-oximes (Scheme 15).25 This rules out a direct displacement and indicates that the products are derived by addition of the better nucleophile, piperidine, to the nitroso-alkenes in a step which is not rate-determining. 44 M. Ohno and N. Naruse, Bull. Chem. SOC.Jpn., 1966, 39, 1125. "M. Masaki, K. Fukui, and M. Ohta, J. Org. Chem., 1967, 32, 3564; G. Gaudiano, R. Mondelli, P.P. Ponti, C. Ticozzi, and A. Umani-Ronchi, J. Org. Chem., 1968, 33, 4431. Gilchrist major product7-H& > cNwNoH2+F=I; XN0 C1 -%MeowNoHminor Reagents: i, C,Hl1N; ii, MeO-; in equimolar amounts product Scheme 15 An investigation of the reaction of syn-and anti-a-bromo-acetophenone oximes with morpholine in aqueous buffer also implicated a vinyl-nitroso compound, a-nitrosostyrene, as an intermediate.' Both bromo-oximes gave the anti-morpholino-oxime as the product.It is suggested that the bromo-oximes are rapidly deprotonated and that or-nitrosostyrene is then formed by loss of bromide in a rate-determining step. This preferentially adds morpholine when in the transoid conformation (Scheme 16). It ("J 'Ph 'Ph I' Br Scheme 16 The mechanisms of many of the other reactions of nucleophiles with halo- oximes and with bis-chloronitroso compounds have not been established.The following discussion includes examples for which the elimination-addition mechanism appears to be likely, either because of independent evidence for the intermediacy of nitroso-alkenes, or because of the reaction conditions employed. (i) Nitrogen, Oxygen, and Sulphur Nucleophiles. There are many and diverse examples of these nucleophiles reacting with vinyl-nitroso compounds, as Table 2 shows. The reactions go by the general route shown in Scheme 14 but further reactions may follow. For example, chloroacetone oxime and aqueous ammonia gave the tertiary amine (22)46 and similar reactions were observed with oximes 46 G. Matthaiopoulos, Ber., 1898, 31, 2396. 63 Nitroso-alkenes and Nitroso-alkynes Table 2 Addition of Nitrogen, Oxygen, and Sulphur nucleophiles to nitroso-alkenes Nitroso-alkenes Types of’nucleophiles Ref: H,C=C(Me)NO NH3, R2NH 46 H2C =C( Pr)NO RCH(NH,)CO,Et 51 H,C=C( Ph)NO NH3 47 R,NH 11 SCN 49 H2C =C(COMe)NO (H,N),CS, HZNCHZCN, 49 RCH(NH,)CO,Et 52 H,C=C(CO,Et)NO ArSH 53 R R C =C( R 3)N0 NH, , RNHz, H,NOH, 54 (R’ = alkyl or H; R2, R3 = alkyl NO2-, N3- or cycloalkyl) R,NH, ROH, ArSH, 21, 22, 25, 28 SCN, OCOR R3N 9 ClCH=CHNO RNH,, ArNH, 48 Cl,C=CHNO ArNH, 55 ArCH=C(R)NO R,NH, ROH, ArSH, 22,25 R3N 9 kN, SC( =S)OEt 50 RNH,, R,NH, 24 MeOH, MeCO,H, RSH of phenacyl halides.47 Dichloroacetaldehyde oxime reacts with primary amines to give imines (23) derived from the initial adducts by further loss of HCl;48 chloral oxime reacts in a similar way.Reactions with thiocyanate ions leads to the formation of 2-aminothiazole 3-oxides (24) by cycli~ation.~~~~~~~~ (ii) Carbon Nucleophiles. Under this heading, only the reactions of carbanions, and electrophilic substitutions of aromatic substrates, will be considered. Reactions with enamines and other electron-rich alkenes are described separately, as cydoadditions, in Section 4C. 47 H. Korten and R. Scholl, Ber., 1901,34, 1901. 48 H. Lerche, J. Treiber, and T. Severin, Chem. Ber., 1980, 113, 2796. 49 M. Masaki, M. Sugiyama, S. Tayama, and M. Ohta, Bull. Chem. SOC.Jpn., 1966, 39, 2745. 50 A. Dornow, H.-H.Marquardt, and H.Paucksch, Chem. Ber., 1964,97, 2165. 64 GiIchrist Vinyl-nitroso compounds are useful for the alkylation of nucleophilic carbon centres under mild conditions. With highly reactive carbanions or their equi- valents, two moles or more are normally used, the first to generate the vinyl- nitroso intermediate and the second to act as the nucleophile. The generation and subsequent methylation of the nitrosocyclohexene by Me,CuLi illustrated in Scheme 3 provides an e~ample.'~ magnesium bromide EthyL9 and ~henyl-~~ have been used in a similar manner, as base and nucleophile, as has 1-lithiobutyne (Scheme 17).56 Oppolzer and his co-workers have used bromo-oximes as alkylating agents for lithium enolates derived from substituted cyclo-pent an one^;^^^^^ one such reaction is shown in Scheme 18.58 NOCH;, Ph Br NOH NO 4 'NOH /Et (85%)Reagents: i, EtC=CLi, -78 "C; ii, EtCECLi, -20°C Scheme 17 Me HO (92%) Scheme 18 Reactions of nitroso-alkenes with other stabilized carbanions are summarized in Table 3.Sodium ethoxide and ethanol have been used as the base-solvent system in many of these reactions, but sodium carbonate in di~hloromethane'~ and piperidinium acetate in tetrahydr~furan~~ have also been used. The products are 1:l adducts which may exist in solution as open-chain tautomers or in five- or six-membered cyclic forms. 51 M. Masaki and M. Ohta, Bull. Chem. SOC.Jpn., 1963, 36, 922, 1177. 52 M. Sugiyama, M. Masaki, and M. Ohta, Bull.Chem. SOC. Jpn., 1966, 39, 2517. 53 T. L. Gilchrist, D. A. Lingham, and T. G. Roberts, J. Chem. SOC., Chem. Commun., 1979, 1089. 54 M. Ohno, S. Torimitsu, N. Naruse, M. Okarnoto, and I. Sakai, Bull. Chem. SOC.Jpn., 1966, 39, 1129. "T. Sandrneyer, Helu. Chim. Acta, 1919, 2, 234. 56 E. J. Corey, M. Petrzilka, and Y. Ueda, Helu. Chim. Acta, 1977, 60, 2294. 57 W. Oppolzer, M. Petrzilka, and K. Battig, Helu. Chim. Acta, 1977, 60, 2964. 58 W. Oppolzer, K. Battig, and T. Hudlicky, Tetrahedron, 1981, 37, 4359. Nitroso-alkenes and Nitroso-alkynes Table 3 Addition of stabilized carbanions to nitroso-alkenes Nitroso-alkenes Substrates Ref: H2C=C( Me)NO I1,3-diketones /3-keto-esters ? malonic esters 1 59 H,C=C( CMe, )NO Me,CCOCH2C02Et 60 H2C=C( Ph)NO /3-keto-esters 61 dini troalk anes 62 H2C=C( C0Me)NO 1,3-diketones 63 H2C=C( C0,Et)NO PhCH=C(Me)NO CH,(CO2Et),MeNO, MeCOCH,CO,Et I MeCOCH,COPh 1 53 14 9 RCH=C(R)NO 54 ClCH=CHNO 1,3-dicarbonyl compounds I* CH2(C02 Me12 EtOZCCH2CN i I 48 CH2(CN)2 * Adducts have the structure XYC=CHCH=NOH Several of the adducts have been converted, by treatment with acid, into 1-hydro~ypyrroles.~~-61,63 An example is the formation of 3-acetyl-2,5-dimethyl-1-hydroxypyrrole from the adduct of chloroacetone oxime and acetylacetone (Scheme 19).59 Reagent: i, HCI, EtOH Scheme 19 The reactions of sulphur-carbon ylides with nitroso-alkenes to give isoxazolines and a-methylene-oximes have been illustrated earlier (Scheme 10).Nitroso-alkenes are potentially very attractive reagents for electrophilic aromatic substitution because of the mild, non-acidic conditions in which they 59 V. Sprio and P. Madonia, Ann. Chim. (Rome), 1960, 50, 1627. 6o R. Rarnasseul and A. Rassat, Bull. Soc. Chim. Fr., 1970, 4330. 6' V. Sprio and G. C. Vaccaro, Ann. Chim. (Rome), 1959, 49, 2075; V. Sprio and J. Fahra, ihid.,1960. 50, 1635. 62 S. A. Shevelev, V. I. Erashko, and A. A. Faindberg, izu. Akd. Nuuk SSSR, Srr. Khim.,1975. 2725. 63 T. L. Gilchrist, G. M. Iskander, and A. K. Yagoub, J. Chrm. Soc., Chrm. Commun., 1981. 696. Gilchrist are generated and because of the variety of functional groups which they can introduce. In practice, the reaction is limited to the most nucleophilic aromatic and heteroaromatic systems and the most electrophilic nitroso-alkenes.Of the simple benzenoid aromatics, only 1,3- and 1,6dimethoxybenzene and N N-dimethylaniline have been alkylated, and only by the highly electrophilic inter- mediates H,C=C(COR)N0.'4 The reactions with 1,3-dimethoxybenzene are illustrated in Scheme 20.3-Nitrosobut-3-en-2-onealso alkylates 2-naphthol at the 1 -position. NOH (1 : 4) R = H (41%)) R = Me (63%) R = OEt (1 1%) Scheme 20 Reactions with electron-rich heterocyclic compounds are more successful. Pyrrole and 1-methylpyrrole have been alkylated by ethyl bromopyruvate oxime in the presence of sodium carbonate, giving mixtures of the 2-and 3-substitution products.l4 Indole and simple alkyl-substituted indoles react particularly well with vinyl-nitroso compounds of this type.Alkylation invariably takes place at the 3-position, so that if a 3-alkylindole is the substrate, the product is a cycloadduct (25) rather than a substitution product (26). Yields of adducts are good (60-85 %) even when equimolar amounts of bromo-oxime and indole are ~sed.'~,~*With the less aromatic systems furan, dimethylfuran, and benzofuran, the initial products are always cycloadducts (27) and (28)l3*I4although they R &fx ~*y-iYX\OHN 0" Nitroso-alkenes and Nitroso-alkynes Table 4 Alkylation of aromatic heterocycles by nitroso-alkenes Heterocyclic compounds Nitroso-alkene Type of product Ref: X in H2C=C(X)N0 2-substitutedPyrrole C02Et 186:14 143-substituted 2-substituted 1-Met hylpyrr ole COzEt /80:20 143-substituted Indole Ph 38 CO2Et 14 COMe 14 1-Methylindole C02Et 64 2-Methylindole COMe 14 3-Met h ylindole CO2Et 14 COMe 14 N-Methyltetrahydrocarbazole Ph 38 CO2Et 38 COMe 38 Furan Ph 13 COMe 14 C0,Et 14 2,SDimethylfuran Ph 13 COMe 14 Benzofuran COMe 14 are readily isomerized to the open-chain oximes by heat or by treatment with acid.The products isolated result from attack only at the 2-position, even with 2,5-dimethylfuran. Published examples of alkylation of heterocycles by vinyl-nitroso compounds are summarized in Table 4. There is plenty of scope for extending this type of alkylation. C. Cycloaddition Reactions.-Nitroso-alkenes can participate in cycloaddition reactions either as 2n-electron systems, through the nitroso group, or as 47c-electron (heterodiene) systems.There are, so far, no examples of cycloadditions involving only the carbon-carbon double bond. Addition to the nitroso group is a reaction which also occurs with many other classes of nitroso corn pound^.^,^^ This type of cycloaddition of nitroso-alkenes is restricted to compounds which bear at least one, and usually two, halogen substituents on the vinyl group,’ For example, trichloronitrosoethylene undergoes such reactions with several acyclic and cyclic nucleophilic dienes 64 H. C. J. Ottenheijm, R. Plate, J. H. Noordick. and J. D. M. Herscheid, J. Org. Chem., 1982, 47. 2147. 65 J. H. Boyer, in ref.43, p. 215. 68 Gilchrist including b~tadiene,~ ~yclopentadiene,~1-meth~xybutadiene,~ cyclohexadiene,66 and benzene oxide.66 The adducts derived from cyclic dienes are thermally unstable and rearrange above room temperature to epoxy-aziridines (Scheme 21) in a manner analogous to that of the corresponding cyclic peroxides derived from singlet oxygen addition. Trifluoronitrosoethylene (la) has also been shown to undergo cycloaddition at the nitroso group, with tetrafluoroethylene and with chlorotrifluoroethylene, to give 1,2-0xazetines.~ Scheme 21 The other important type of cycloaddition reaction of nitroso-alkenes involves reaction at the terminal carbon and oxygen atoms with nucleophilic alkenes, to give 5,6-dihydro-4H- 1,2-oxazines (29) (Scheme 22).This mode of addition Scheme 22 was first observed between a-nitrosostyrene (lj) and ~yclopentadiene.'~ It is in contrast to other reactions of nitroso compounds with cyclopentadiene, in which the diene adds as a 4.n-electron system across the N=O bond, and also to the reactions of most other activated alkenes in which addition takes place at the electrophilic double bond. The reaction has since been extended to several other nitroso-alkenes, most of which are unsubstituted at the P-carbon atom.7.' 3*14 These intermediates are highly electrophilic, and, in frontier orbital terms, have a large coefficient on the /&carbon atom in the lowest unoccupied molecular orbital (LUMO).'3,36 Reactions with cyclopentadiene are highly regio- and stereo-selective, the isolated adducts having the structures (30).Other acyclic 66 E. Francotte. R. Merenyi, and H. G. Viehe. Anyew. Chem., Int. Ed. Engl., 1978, 17, 936. Nitroso-alkenes and Nitroso-alkynes and cyclic conjugated dienes add in the same way to nitroso-alkenes of the general type H,C=C(X)NO. 7,1 3,14,67 or-Nitrosostyrene has not been intercepted by simple alkenes, but it will form adducts in low yields with indene, or-methylstyrene, and other conjugated alkenes. When the substituent X in the nitroso-alkene H,C=C(X)NO is also a con-jugatively electron-withdrawing group, however, addition occurs even with simple alkenes.12.14 More nucleophilic alkenes, such as enol ether^'^.^^ and enamine~,'~.~~add very well to these intermediates and give high yields of the adducts (29).These reactions show the general characteristics expected for Diels-Alder cycloadditions 'with inverse electron demand'; that is, with electron- deficient heterodienes and electron-rich alkenes. Since all the nitroso-alkenes are transient species, no direct rate measurements are possible, but the reactions are most efficient for alkenes with a high-lying HOMO and with vinyl-nitroso compounds with a low-lying LUMO. Competition experiments with the addition of pairs of alkenes to 3-nitrosobut-3-en-2-one showed that adducts are formed preferentially with the more nucleophilic alkenes. l4 The reactions show high stereoselectivity, and the observed regioselectivity of the additions is also in accord with that expected on the basis of the HOMO coefficients of the alkenes.No examples of addition with 'normal electron demand', that is, between a nucleophilic nitroso-alkene and an electrophilic alkene, have been observed ; an attempt to perform such a reaction between nitrosocyclohexene and maleic anhydride was unsuccessfu1.69 Typical examples of cycloadditions of this type, following the general pattern of Scheme 22, are shown in Table 5. These reactions thus represent a simple method of functionalization of alkenes. The closest analogies to these reactions are the cycloadditions of vinyl-nitrosonium salts (3 1) which have been extensively studied by Eschenmoser and his co-~orkers.~' Conjugated nitro-alkenes can also add in this manner to highly nucleophilic alkenes such as enamine~.~~ The 1,2-oxazines (29) can be cleaved reductively at the N-0 bond53,68 and thermally or by acid at the C-0 bond.58,72,73These reactions make the oxazines potentially useful for the synthesis of pyrr~les,~~,~~ y-la~tones,~~pyridine~,~~.~, and esters of or-amino-acid~.~~ Analogous adducts have not been isolated from other nucleophilic multiple bonds.No adduct could be isolated from a reaction between 3-nitrosobut-3-en- 2-one and phenylacetylene, or with (diethylamino)propyne, although the ynamine did undergo a reaction. a-Nitrosostyrene has been shown to add to the C=N b7 G. M. Iskander and V. S. Gulta, J. Chem. SOC.,Perkin Trans. 1, 1982, 1891. P. Bravo, G. Gaudiano, P.P. Ponti, and A. Umani-Ronchi. Tetrahedron, 1970, 26, 1315; S. Nakanishi, Y. Shirai, K. Takahashi, and Y. Otsuji, Chem. Lett., 1981, 869. G. Just and W. Zehetner, Chem. Commun., 1971, 81. 70 U. M. Kempe, T. K. DasGupta, K. Blatt, P. Gygax, D. Felix, and A. Eschenmoser, Helv C'hlm. Acta, 1972. 55, 2188; M. Riediker and W. Graf, Helv. Chim. Acta, 1979, 62, 205; M. Riediker and W. Graf, Angew. Chem., Int. Ed. Engl., 1981, 20,481. 71 A. Risaliti, M. Forchiassin, and E. Valentin, Tetrahedron, 1968, 24, 1889. 72 R. Faragher and T. L. Gilchrist, J. Chem. SOC., Perkin Trans. 1, 1979, 258. 73 T. L. Gilchrist and T. G. Roberts, J. Chem. SOC.,Chem. Commun., 1979, 1090. Gilchrist Table 5 Examples of cycloaddition of nitroso-alkmes to atkenes Alkene Nitroso-alkene Adduct (29) :; Yield R e$ XinH,C=C(X)NO R’ R2 R3 a-Methylstyrene Ph H Me Ph 26 12 C6H4NO2-4 83 12 COMe 43 14 CHO 39 14 C02Et 43 14 (E)-Stilbene Ph Ph H Ph 5 12 C6H4N02-4 57 12 COMe 46 14 CHO 13 14 Oct-1-ene CCH4N02-4 H H C,H,,1 (85:15) C6H13 40 12 COMe H H CbH,, 31 14 Ethyl vinyl ether Ph H H OEt 87 58 COMe 82 14, 58 1-Morpholino-Ph -(CH2)4-NR2 91 68 cyclohexene C02Et 86 68 bonds of some 1,2-0xazines,~~ although this is not a general reaction of C=N bonds.The products are [3 + 21 rather than [4 + 21 cycloadducts, addition having taken place at the nitrogen atom of the nitrostyrene. Similar adducts are also found as minor products in the addition of some electron-rich alkenes to a-nitro~ostyrene:’~.~~for example, 2-methoxypropene gives the nitrone (32) (10%) as well as the expected dihydro-oxazine.” The ratio of adducts is insensi- tive to the polarity of the solvent or to the stereochemistry of the halo-oxime precursor. If concerted, these [3 + 21 additions would require the nitrosostyrene to add through a twisted conformation, (33), as a type of 1,3-dipole.(32) (33) D. Other Reactions.-There are few other well-established reactions of these compounds. Nitrosocyclohexene* and trifluoronitroso-ethylene4 have been observed to undergo electrophilic addition by chlorine; hydrogen chloride also adds to some nitro~o-alkenes.~~~ There are no well authenticated examples of radical additions or of ene reactions which are common with other types of nitroso compounds.Some nitroso-alkenes2’ and trifluoronitr~soethylene~are claimed to polymerize in solution, the latter by a radical mechanism. 74 D. Mackay and K. N. Watson, J. Chem. SOC.,Chem. Commun., 1982, 775. 71 Nitroso-alkenes and Nitroso-alkynes 5 Nitroso-alkynes The preparation of several nitroso-alkynes was attempted by Robson, Tedder, and Woodc~ck,'~ who treated metal alkynides with nitrosyl chloride. Better results were obtained with mercury alkynides than with magnesium alkynides. Green solutions containing several nitroso-alkynes (2) were obtained at low temperatures. The spectroscopic properties observed for two of these inter- mediates (a, R = Bun and b, R = Bu') are summarized in Scheme 23. The t-butyl compound (2b) has also been obtained by reaction of the corresponding trimethylstannylalkyne with dinitrogen tetr~xide.~~ (R-,--)ZHg +R----NO (2) a; R = Bu b; R = CMe3 Reagent: i, NOCl, -60 "C (2a): v,,, 2290 (C5C) and 1580 (N=O) cm-'; A,,, 640 nm (2b): vmax 2320--2280 (C=C) and 1560 (N=O) cm-'; Lmax654 nm Scheme 23 Compound (2b) rearranges in ether (4h, -30°C) to pivaloyl cyanide, Me3CCOCN,' 5*75 and can be oxidized by hydrogen peroxide to the corresponding nitro-alk~ne.~~Deoxygenation by triethyl phosphite in the presence of 2,3-dimethylbut-2-ene gave the adduct (34) (Scheme 24):75 the nitrene formed by deoxygenation apparently adds to the alkene through a mesomeric carbene structure.Me3C-CCC-NO -!-+ MeJC-CEC-N +--+ Me3C -C-CEN Pi Me Me (34) Reagents: i, P(OEt),, -40°C; ii, Me,C=CMe, Scheme 24 The less hindered 1-nitrosohexyne (2a) dimerizes in the presence of base to the furoxan (35)," and forms a different furoxan, (36), in the presence of nitrosyl chloride and aniline.76 ''J.-C. Motte and H. G. Viehe, Chimia, 1975, 29, 515. 76 J. M. Tedder and D. J. Woodcock, J. Chem. Res. (S), 1978, 356; J. Chem. Res. (M), 1978, 4356. 72 Gilchrist A reaction in which nitroso-acetylene itself may have been generated is illustrated in Scheme 25: the bromo-oxime (37) gave the naphthalene (38) on heating with base, probably by a retro-Diels-Alder process.77 Attempts to intercept the nitroso-acetylene were unsuccessful. Bu \kNt N Bu 0’ \O‘ (35) Me + c1 \ Me t [HC ECNO] c1 CI c1 Reagent: i, Et,N, d.rn.f., 100 “C Scheme 25 ” P. C. Buxton, H. Heaney, K. G. Mason, and J. M. Sketchley, J. Chem. Soc., Perkin Trans. I, 1974,2695.

ISSN:0306-0012    

DOI:10.1039/CS9831200053

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

Stereoselective Synthesis of Steroid Side-chains By J. Redpath ORGANON, SCIENTIFIC DEVELOPMENT GROUP, NEWHOUSE ML1 5SH, UNITED KINGDOM F. J. Zeelen ORGANON, SCIENTIFIC DEVELOPMENT GROUP, OSS 5340 BH, THE NETHERLANDS 1 Introduction The discovery of interesting steroids with modified side-chains (Figure l), such as the vitamin D rnetabolites,'i2 ~ithaferin-A~.~and other withanolides with anti-tumour a~tivity,~*~" the insect moulting hormones,6*6u the plant growth promoters bra~sinolide,'.~" castasterone' and dolicholide,*" the sex stimulating steroids antheridiolg and oogoniol lo*ll of the watermould Achlya, and all types of marine steroids,12 has stimulated the search for stereoselective syntheses of steroid side-chains. An added incentive has been the development of efficient microbiological methods for the production of androsta-1,4-diene-3,17-dione,androst-4-ene-3,17-dione, and 9a-hydroxyandrost-4-ene-3,l7-dione. These processes have made 17-keto-steroids available as starting materials for the preparation of cortico-steroids.' Earlier work in this field was reviewed in 1972 by Oliveto14 and again in ' H.F. de Luca and H. K. Schnoes, Annu. Rev. Biochem., 1976, 45, 631. H. Jones and G. Rasmussen. Prog. Chem. Org. Natural Prod., 1980, 39, 64. A. T. McPhail and G. A. Sim, J. Chem. SOC.B, 1968,962.' M. Hirayama, K. Gamoh, and N. Ikekawa, Tetrahedron Lett., 1982, 23, 4725. 1. Moriguchi and K. Komatsu, Eur. J. Med. Chem., 1981, 16, 19. 5a M. Hirayama, K. Gamoh, and N. Ikekawa, Chem.Lett., 1982, 491. ' R. Lafont, P. Beydon, G. Somme-Martin, and C. Blais, Steroids, 1980, 36, 185. P.Cherbas, D. A. Trainor, R. J. Stonard,and K. Nakanishi, J. Chem. SOC., Chem. Commun., 1982,1307. M. D. Grove, G. F. Spencer, W. K. Rohwedder, N. Mandava, J. F. Worley, J. D. Warthen, jun., G. L. Steffens, J. L. Flippen-Anderson, and J. C. Cook, Nature, 1979, 281, 216. "M. Sakakibara, K. Okada, Y. Ichikawa, and K. Mori, Heterocycles, 1982, 17, 301. T. Yokota, M. Arima, and N. Takahashi, Tetrahedron Lett., 1982, 23, 1275. T. Yokota, J. Baba, and N. Takahashi, Tetrahedron Lett., 1982, 23, 4965. G. P. Arsenault, K. Biemann, A. W. Barksdale, and T. C. Morris, J. Am. Chem. SOC., 1968, 90, 5635. lo T. C. McMorris, S. R. Schow, and G.R. Weihe, Tetrahedron Lett., 1978, 335. 'I J. R. Wiersig, N. Waespe-Sarcevic, and C. Djerassi, J. Org. Chem., 1979, 44, 3374. l2 C. Djerassi, Pure Appl. Chem., 1981, 53, 873. I' M. G. Wovcha, F. J. Antosz, J. C. Knight, L. A. Kominek, and T. R. Pyke, Biochem. Biophys. Acta, 1978, 531, 308. " E. P. Oliveto, in 'Organic Reactions in Steroid Chemistry,' ed. J. Fried and J. A. Edwards, Van Nostrand Reinhold Company, New York, 1972, Vol. 11, chapter 11. 75 Stereoselective Synthesis of' Steroid Side-chains H 1,25,26-TrhydroxyvitaminD3 Witliafeiin A An theridiol Oogoniol 0H HO HO H x -Ecdysone Brassinolidc Figure 1 Steroids with modified side-chains Redpath and Zeelen 1978 by Piatak and Wicha.” The Solanurn,’6 Verutrurn, and Buxus” alkaloids, as well as the cardenolides’* have also been reviewed extensively. Hardly any synthetic work has been reported on the sapogenins.” In the present review we limit discussion to the major principles of side-chain stereoselective syntheses as illustrated in the recent literature (1978-September 1982).The notation of the stereochemistry of the side-chain is a difficult problem in a review of this nature. The Cahn, Ingold, and Prelog notation2* is precise but priorities sometimes change with differences in substitution. For example, both a-ecdysone and brassinolide are 22R-hydroxy-steroids although they have opposite configuration. The Fischer-Plattner-Fieser-Fieser convention21 does not suffer from this disadvantage but confusion has arisen through the introduc- tion of the van Nes convention,22 which unfortunately uses that same ap-designa- tion.Thus, brassinolide is 22a,23a- using the van Nes convention23 but 22aF ,23pF- using the Fischer convention. In this review the Fischer convention will be used where necessary and indicated by the subscript F (Fischer), in line with earlier suggestion^.^^ 2 Strategy As illustrated in Scheme 1, reactions of the 17-keto-group can be highly stereo- selective with the effect diminishing as we proceed along the flexible side-chain to C-20 and C-22, and disappearing in the 23- and 24-keto-steroids. Consequently, chiral centres can be introduced by diastereoselective reactions, but at C-22 part of the specificity is lost.The availability of 3-hvdroxypregn-5-ene-20-carboxaldehyde as a cheap technical product has, however, encouraged its use as a starting material, despite the need to separate the mixture of isomers formed. The use of chiral reagents, although little explored in this area, can be complementary. Schonemann and van Vliet3’ studied the reduction of 3-methoxyestra-1,3,5(1O)-trien-17-onewith the chiral complexes of (+)-or (-)-IS D. M. Piatak and J. Wicha, Chem. Rev., 1978, 78, 199. 16 H. Ripperger and K. Schreiber, in ‘The Alkaloids,’ ed. R. H. F. Manske and R. G. A. Rodrigo, Academic Press, New York, 1981, Vol. 19, p. 81. 17 J. Tomko and Z. Voticky, in ‘The Alkaloids,’ ed. R. H. F. Manske, Academic Press, New York, 1973, Vol. 14, p. 1.18 P. G. Marshall, in ‘Rodd’s Chemistry of Carbon Compounds,’ 2nd edition, Elsevier Publishing Company, Amsterdam, 1970, IID, p. 360. 19 J. Elks, in ‘Rodd’s Chemistry of Carbon Compounds.’ 2nd edition, Elsevier Publishing Company, Amsterdam, 1971, HE, p. 1. 20 R. S. Cahn, C. Ingold, and V. Prelog, Angew. Chem., Int. Ed. Engl., 1966, 5, 385. 21 L. Fieser and M. Fieser, ‘Steroids,’ Reinhold Publishing Corporation, New York, 1959, p. 337. 22 W. R. Nes, Adv. Lipid Res., 1977, 15, 233. 23 M. J. Thompson, N. B. Mandava, W. J. Meudt, W. R. Lusby, and D. W. Spaulding, Steroids, 1981, 38, 567. 24 L. F. Fieser and M. Fieser, Tetrahedron, 1960, 8, 360. 25 H. J. Ringold, B. Lohen, G. Rosenkranz, and F. Sondheimer, J. Am. Chem. SOC., 1956, 78, 816.26 D. C. Ayres and R. Sawday, J. Chem. SOC.(B), 1967, 581. 27 E. P. Burrows, G. M. Hornby, and E. Caspi, .I. Org. Chem., 1969, 34, 103. 28 N. Entwistle and A. D. Pratt, Tetruhedron, 1969, 25, 1449. 29 J. Zielinski, H. Li, and C. Djerassi, J. Ory. Chem., 1982, 47, 620. 30 K. H. Schonemann and N. P. van Vliet, personal communication. 77 Stereoselective Synthesis of Steroid Side-chains &ratio 1 : 1 OMe OMe Scheme 1 (2S,3K)-4-dimethylamino-3-methyl-1,2-diphenylbutan-2-0l.~'The effect was small. The complex with the (+)-alcohol shifted the 17p:17cr ratio of the 3-methoxyestra-1,3,5( lO)-trien-17-oIs from the usual 97: 3 to 93 :7, whereas the complex with the (-)-alcohol gave a 99:l mixture. On the other hand, Ishiguro et al.32 achieved reduction of a 24-keto-steroid to 24-hydroxy-steroids with 31 S.Yamaguchi and H. S. Mosher, J. Org. Chem., 1973, 38, 1870. 32 M. Ishiguro, N. Koizumi, M. Yasuda, and N. Ikekawa, J. C'hem. Soc.. Chem. Commun., 1981. 115. 78 Redpath and Zeelen 95 enantiomeric purity with complexes of LiAlH,, ethanol, and 2,2‘-dihydroxy-l,l’-binaphthyl. Other possible methods of introducing the desired chirality are through condensation with a chiral fragment32“-36 and by chirality transfer from another centre through reactions with a rigid transition-state, such as the Claisen rearrangement (Scheme 2).37,38 I ti I Scheme 2 Syntheses Starting from 17-Ket~nes.--The least hindered approach of the nucleophilic reagent is from the or-side.Consequently, reactions under kinetic conditions, with a transition-state close to the starting compound, yield mainly 17a-substituted- 17P-hydroxy-steroids. For example, ethynylation of 38-acetoxyandrost-5-en-17-one(1) with potassium acetylide in t-butanol yields the 17a-ethynyl-17/l-hydroxy-steroid (2) with only 0.3”/, of the isomer (3).39 Under equilibrating conditions somewhat more of the 17/l-ethynyl-l7a-hydroxy-isomers are formed.40 320 P. J. Kocienski, B. Lythgoe, and D. A. Roberts, J. Chem. Soc., Perhin Trans. 1, 1978, 834. 33 H. Takayama, M. Ohmori, and S. Yamada, Tetrahedron Lett., 1980, 21, 5027. 33a S. Yamada, M. Ohrnori, H. Takayarna, T. Suda, and Y. Takasaki, Chem. Phurm. BulI., 1981.29, 1187. 34 J. J. Partridge, S. J.Shiuey, N. K. Chadha, E. G. Baggiolini, J. F. Blount, and M. R. Uskokovic, J. Am. Chetn. Soc., 1981, 103, 1253. 35 S. Yarnada, K. Nakayarna, and H. Takayama, Tetrahedron Lrtt., 1981, 22, 2591. 36 S. Yamada, K. Nakayarna, and H. Takayama, Chern. Pharm. Bull., 1981. 29, 2393. 37 W. Sucrow and B. Girgersohn, Chem. Ber., 1970, 103, 750. 38 W. Sucrow, B. Schubert, W. Richter, and M. Slopianka, Chem. Ber., 1971, 104, 3689. 39 T. Reichstein and C. H. Meystre, Helc. Chim. Actu, 1938, 22, 728. ‘O R. M. Konojia, G. 0.Allen, J. M. Killinger, and J. L. McGuire, J. Med. Chrm., 1979, 22, 1538. Stereoselectioe Synthesis of Steroid Side-chains OH CECH OH CN Scheme 3 Teichmiiller showed that the reaction of 17-keto-steroids with acetone cyanohydrine in aqueous alcohol at pH 8.5-9 yields, after a short reaction time, the 17a-cyano-17~-hydroxy-steroid(4)as the kinetic product.By using a high concentration and longer reaction times the less soluble 17P-cyano- 17a- hydroxy-steroid (5) was obtained in 98 % The 17fl-cyano-17ct-hydroxy-steroid (5) can be converted, after protection of the 17-hydroxy-group as an ether, into a 17a-hydroxy-20-keto-steroidusing a Grignard reaction. The 17a-ethynyl-17fl-hydroxy-steroids are important starting materials. Reac- tion of a nucleophile at the 21-position may result in trans addition to the acetylenic bond or in allene formation. The pregn- 17-en-21-als can, after reduction to the 21-01s and acetylation, be oxidized stereoselectively to give the dihydroxyacetone side-chain characteristic for the cortic~steroids.~~ The oxidation of an allene with OsO, to give this side-chain has also been de~cribed.~' The yield was only 53 however.An interesting variation is based on the unsaturated sulphoxide-sulphenate rearrangement5 (Scheme 6). Its overall yield was 63 %. Other examples of the use of this rearrangement can be found in the synthesis of 3-methoxy-19-norpregna-1,3,5(10),17(2O)-tetraene-20-~arbaldehyde,~~38-41 G. Teichmuller, 9th Conference on Isoprenoids, Prague, 1981. 42 G. Teichmuller, G. Haessler, K. Barnikoloc, G. Grinenko, and E. Dolginowa, GDR patent 147669. 43 J. C. Gasc and L. Nedelec, Tetrahedron Lett., 1971, 2005. 44 K. Ponsold and W. Schade, 2. Chem., 1975, 15, 148. 45 K.Ponsold and W. Schade, GDR patent 112124. 46 L. A. van Dijck, K. H. Schonemann, and F. J. Zeelan, Red. Trav. Chim. Pays-Bas, 1969, 88, 254 47 C. J. Elsevier, J. Meijer, H. Westmijze, P. Vermeer, and L. A. van Dijck, J. Chem. SOC., Chem Commun., 1982, 85. 48 G. L. Olson, K. D. Morgan, and G. Saucy, Synthesis, 1976, 25. 49 J. A. Hogg, P. F. Beal, A. H. Nathan, F. H. Lincoln, W.P. Schneider, B. J. Magerlein, A. R. Hanze, and R. W. Jackson, J. Am. Chem. SOC.,1955, 77, 4436. 50 M. Biollaz, W. Haefliger, E. Velarde, P. Crabbe, and J. H. Fried, Chem. Commun., 1971, 1322. 51 V. V. van Rheenen and K. P. Shephard, J. Org. Chem., 1979, 44, 1582. 52 B. M. Trost and J. L. Stanton, J. Am. Chem. SOC.,1975, 94, 4018. 80 Redpath and Zeelen 74% (l..f; 44, 45) OH MeC =CMe LiAlH 4 -56% 32%) (PhSi0)2V(0)0, .H (wj.46, 47) c ,/c =CH II ‘I\c JCH0 (Ph3SiO)3VO Ph3SiOH -6-fi 79% Scheme 4 (wf.48) rOR OsO4 / c--0s04 Scheme 5 ethoxy-21-methylpregna-5,17(20),20-triene,’3chole~terol,~~25-hydroxycholes-ter01,’~ and 20,22~,-dihydroxycholesterol(Scheme 21).’ Despite the ready occurrence of these rearrangements of 17-este1-s~~it proved possible, with proper choice of ester, nucleophile, catalyst, and solvent, to achieve nucleophilic substitution with inversion of the side-chain.Methanesulphonate esters could be replaced by an hydroxy-group using Ag’ and tetrahydrofuran- 53 G. Neef, U. Eder, and A. Seeger, Tetrahedron Lett., 1980, 21, 903. ’4 M. Ohmori, S. Yamada, H.Takayama, and K. Ochi, Tetrahedron Lett., 1982, 23, 4709. ” K. S. Kyler and D. S. Watt, J. Org. Chem., 1981, 46, 5182. 56 W. R.Benn, J. Org. Chem., 1968, 33, 313. 81 Stereoselective Synthesis of Steroid Side-chains 0&-OH Scheme 6 t-l il Me0 (ref. 57) H &:ECH 0 Ag+ _347% ___)62% 5 1 ‘i: Scheme 7 Redpath and Zeelen ~ater,~'and nitrate esters by formate using Ag' and formic acid in hexamethyl- phosphortriamide5* (Scheme 7). Free-radical addition of thiols to an ethoxyethynylsteroid was studied by Sperna Weiland and Arens." The addition product was rearranged to the enal, reduced, and converted into the ketol in 47-51 % overall yield. Ft0tl r0f I Scheme 8 Wittig Reactions and Aldol Condensations of 17-Keto-steroids.-Reaction of 17-keto-steroids with non-stabilized ylides yields mainly the Z-alkenes,60- 62 whereas reaction of stabilized ylides leads to the more stable E-i~omers.~~-~~ Aldol condensations of steroidal 17-ketones with other ketones result mainly in the formation of 16-substituted steroids, consequently for the elaboration of 17-ketones into pregnanes or sterols only Knoevenagel condensations with esters can be 57 H.Westmijze, H. Kleyn, P. Vermeer, and L. A. van Dijck, Tetrahedron Lett., 1980, 21, 2665. 58 H. Hofmeister, K. Annen, H. Laurent, and R. Wiechert, Chem. Ber., 1978, 111, 3086. 59 H. Sperna Weiland and J. F. Arens, Red. Trav. Chim. Pays-Bas, 1960, 79, 1293. 6o A. M. Kubriner and E. P. Oliveto, J.Org. Chem., 1966, 31, 24. 61 S. Danishefsky, K. Nagasawa, and N. Wang, J. Org. Chem., 1975, 40, 1989. 62 C. Y. Byon and M. Gut, J. Org. Chem., 1980, 45, 4404. 63 M. L. Raggio and D. S. Watt, J. Org. Chem., 1976, 41, 1873. 64 J. Wicha, K. Bal, and S. Piekut, Synth. Commun., 1977, 7, 215. 65 J. Wicha and K. Bal, J. Chem. SOC., Perkin Trans. I, 1978, 1282. 66 W. Nagata and Y. Hayaze, J. Chem. SOC. (C), 1969, 460. " G. Haffer, U. Eder, G. Neef, G. Sauer, and R. Wiechert, Chem. Ber., 1978, 111, 1533. 68 U. Schollkopf and K. Hantke, Chem. Ber., 1976, 109, 3964. 69 L. Nedelec, V. Torelli, and M. Hardy, J. Chem. Soc., Chem. Commun., 1981, 775. 'O G. Neef, U. Eder, A. Seeger, and R. Wiechert, Chem. Ber., 1980, 113, 1184. 83 Stereoselective Synthesis of Steroid Side-chains 0 MeCOO& cool.!3 Scheme 9 0 0 88% Scheme 10 EtO&i.ii. LiCH(CO0Mc)OMe SOC12-py 3cooMe 7670 Scheme 11 84 Redpath and Zeelen In the last example7' the aldol was isolated and dehydrated in a separate step. This compound can also be prepared via a Reformatsky-type reaction using ethyl trichloroacetate, zinc, and diethylchloro-aluminum to give the methyl 20-~hloropregnenoate, which is then treated with sodium meth~xide.~' The use of l-[(isocyanomethyl)sulphonyl]-4-methylbenzene (TOSMIC) as a potential route to progesterone and derivatives via 17-cyano-steroids was disappointing in that it yielded a mixture of isomers at position-17.72 M Scheme 12 '' '* A.R. Daniewski and W. Wojciechowska, J. Org. Chem., 1982, 41, 2993. J. R. Bull and W. R. Tuinrnan, Tetrahedron, 1975, 31, 2151. Stereoselective Synthesis of Steroid Side-chains Reactions of 17(20)-Pregnenes.-The ethylidene derivatives are useful inter- mediates. Selective hydroboration with 9-borabicyclo[3.3. llnonane proceeds in a stereoselective manner from the a-side. The borane derivatives can then be treated with alkaline hydrogen peroxide to give the alcohols or with chloro- acetonitrile to give cyano-~teroids.~~.~~ Ene reactions also proved possible without touching the 5(6)-double The use of (n-ally1)Pd complexes for H gcooMe HC =CCOOMe -Et2 AlCl MeCOO MeCOO 7 1-98% Scheme 13 synthesis of the steroid side-chain was explored by Trost and Verhoeven.*' Following activation of the complex with a phosphorus ligand, alkylation was possible but the product obtained had unnatural stereochemistry at C-20, resulting from a trans approach to the a-substituted Pd group.A product with a natural configuration at C-20 was obtained using alkenylzirconium reagent, 73 M. M. Midland and Y. C. Kwon, J. Org. Chem., 1981,46,229. 74 M.M.Midland and Y. C. Kwon, Tetrahedron Lett., 1982,23,2077. 75 W.G.Dauben and T. Brookhart, J. Am. Chem. Soc., 1981,103,237. 76 A. D. Batcho, D. E. Berger, M. R. Uskokovic, and B. B. Snider, J. Am. Chem. Soc., 1981, 103, 1293. 77 A. D. Batcho, D. E. Berger, S. G. Davoust, P.M. Wovkulich, and M. R. Uskokovic, Helc. Chim. Acta, 1981,64, 1682. 78 E.G. Baggiolini, J. A. Jacobelli, B. M. Hennessy, and M. R. Uskokovic, J. Am. Chrm. Soc.. 1982, 104,2495. 79 W. G. Dauben and T. Brookhart, J. Org. Chem., 1982,47,3921. B. M. Trost and T. R. Verhoeven, J. Am. Chem. Soc., 1978,100, 3435. 86 Redpath and Zeelen L J2 K NaCH(COOMe)2 I COOMe Scheme 14 which is known to give a cis approach. In this case, however, the regioselectivity was poor.81-83 Another disadvantage of these reactions is the need to use stoicheiometric amounts of expensive palladium salts. Both problems were overcome when it was discovered that allylic acetates could be alkylated following complex formation with catalytic amounts of Pdo complexes.80984 This reaction sequence was used to synthesize Sa-cholestanone and ecdysone.Another application of Scheme 15 this Pd-catalysed reaction is the synthesis of 24-hydroxycholestero1 derivatives from A23-22-acetoxycholesterolderivative^.^^ The 20-alkylation of E-15/?,16~-oxidopregna-5,17(20)-dien-3-01dimethyl-t-butylsilylether is also determined by the steric preference for or-face approach.86 J. S. Temple and J. Schwartz, J. Am. Chrm. Soc., 1980, 102, 7381. Y. Hayasi, M. Riediker, J. S. Temple, and J. Schwartz, Tetrahedron Lett., 1981, 22, 2629. 83 M. Riediker and J. Schwartz, Tetrahedron Lett., 1981, 22, 465.5. 84 B. M. Trost and Y. Matsarnura, J. Org. Chem., 1977, 42, 2036. 85 S. Takatsuto, M. Ishiguro, and N. Ikekawa, J. Chem. Sac., Chem. Commun., 1982, 2.58. 86 J. P. Marino and H. Abe, J. Am. Chem.SOC., 1981, 103, 2907. 87 Stereoselective Synthesis of Steroid Side-chains CH20COMe 6:H+ ___) ( wj.71) 98% Scheme 16 The reactivity of the 17(20) double bonds depends strongly on the substituents. Electron-withdrawing groups deactivate this bond towards electrophilic substitu- tion (Scheme 16). In practice a high reactivity of the 17(20) double bond is necessary to prevent reaction with other double bonds in the molecule. For that reason it is best that a$-unsaturated esters are first reduced to alcohols before carrying out substitutions at the double bond. Recent work has been concentrated on finding routes to good activating groups. For example, Neef et d7'explored ---20f 1 84%Scheme 17 Redpath and Zeelen the use of enol ethers (Scheme 17).The use of enamides was explored by Barton et and by Nedelec et~1.~~7~~ Reactions of Carbanions at Position-20.-Electron-withdrawing groups at the 20-position promote the formation of carbanions at the 20-position, through hydrogen abstraction, and this opens up a series of synthetic possibilities (Scheme 18).89990 The nitro-group of the last mentioned compound in Scheme 18, for example, could be reduced to the oxime and then hydrolysed to the 20-ketone. CH2OH fi HCo“, ANo2 quant. (r~f.90) Scheme 18 The anions can also be generated when no double bond is present.” Raggio and Watt63 and Haffer et used the anionic oxidation to convert 20-cyano- pregnanes into 20-ketopregnanes. A high stereoselectivity was found for the alkylation of the pregnenals’’ and the pregnen~ates,~’ leading to products with the configuration of the natural sterols.The high stereoselectivity was retained when a chiral centre was present in the alkyl chain and this made possible a stereoselective synthesis of both 25S,26-and 25R,26-dihydroxycholecalciferol.34~92 Reactions of the 20-Carbonyl Group.-The stereochemistry of reactions of functional groups on a flexible side-chain is dependent on conformational preferences. Since these may vary with different substituents, stereochemical guidelines of a general nature can not be defined. D. H. R.Barton. W. 9. Motherwell, and S. Z. Zard, J. Chem. Soc.. Chem. Cornmun., 1981, 774.** D. H. R. Barton. W. B. Motherwell, and S.Z. Zard, Nouv. J. Chim., 1982, 6, 295. 89 R. R.Wroble and D. S. Watt, J. Org. Chem., 1976, 41, 2939. 90 D. H. R. Barton, W. B. Motherwell, and S. Z. Zard, J. Chem. Soc., Chem. Cornmun., 1982, 551. 91 Y. Letourneux, G. Bujuktur, M. T. Ryzlak, A. K. Banerjee, and M. Gut, J. Org. Chem., 1976,41,2288. 92 J. J. Partridge, S. J. Shuey, N. K. Chadha, E. G. Baggiolini, B. M. Hennessy, M. R. IJskokovic, J. L. Napoli, T. A. Reinhardt, and R. L. Horst, Helv. Chim. Acta, 1981, 64, 2138. 89 Stereoselective Synthesis of Steroid Side-chains EtOOC YH 80-852 H 80% %heme 19 For example, whereas Grignard-type additions to unsubstituted 20-ketone~~~.~’ and 20-aldehyde~~~ yield mixtures with some preference for products resulting from approach from the 20aF-side, Makino et found that reaction of ~1.~~9~~ labelled MeMgI with a 17a-hydroxy-20-keto-steroidgave 99 ”/, of the S-isomer (20aF-approach) but with a 16a,17a-epoxy-20-keto-steroidyielded 93 ”/; of the R-isomer (20&approach). In contrast to Grignard reagents, high stereoselectivity was reported for the addition of dimethylsulphoxonium methylide, to give the 20R-0xide.’~ A 20R-oxide could also be synthesized via stereoselective addition of methylselenomethyl- lithium.” These oxides react in the normal fashion with 2-lithio-2-isobutyl- 1,3-dithiane but rearrange into 20-iso-2 1-aldehydes during Grignard reactions or by treatment with Lewis acids.This opened a route to 20-i~osterols.~~- loo High stereoselectivity was achieved by Kyler and Watt55 (Scheme 21).Enolization of the 20-ketone was, however, a competing side-reaction so that the yield was only moderate. As shown in Scheme 21, the product was converted into the dianion and C-alkylated with high stereoselectivity, although O-alkyla- tion was a competing reaction. After removal of the silyl group, with inversion 93 W. R. Nes and T. E. Varkey, J. Org. Chem., 1976, 41, 1652. 94 M. Koreeda, N. Koizumi, and B. A. Teichler, J. Chem. SOC.,Chem. Commun., 1976, 1035. 95 V. Pouzar and R. Havel, Collections, 1981,46, 2758. 96 Y. Osawa, T. Makino, K. Shibata, C. M. Weeks, and W. L. Duax, J. Chem. SOC., Chem. Commun.. 1976,991. 97 T. Makino, K. Shibata, D. C. Rohrer. and Y. Osawa, J. Org. Chem., 1978, 43, 276.98 M. Koreeda and N. Koizumi, Tetrahedron Lett., 1978, 1641. 99 J. R. Schauder and A. Krief, Tetrahedron Lett., 1982, 23, 4389. loo W. Sucrow and M. van Nooy, Liebigs Ann. Chem., 1982, 1897. 90 Redpath and Zeelen Scheme 20 of configuration at C-24, the sulphide was oxidized to sulphoxide and subjected to [2,3]sigmatropic rearrangement, as discussed earlier in this review. Reduction of the sulphinate ester, selective hydrogenation, and removal of the protecting group at C-3 gave dihydroxycholesterol. An approach to ecdysone side-chain synthesis used the coupling of 2-lithio-5-methylfuran with 20-keto-steroids, followed by dehydration to the 20-pregnene, which could then be hydrogenated to the 20s-steroid. 'OoO These reactions proceeded with a remarkable selectivity. Wittig Reactions.-Wittig reactions of 3/3-hydroxypregn-5-en-20-onewith non- stabilized ylides have been noted to give solely the E-isomer.'"- '04 Selective catalytic hydrogenation then yields a mixture of the 20R- and 20s-isomers in a ratio that is strongly dependent on the exact hydrogenation conditions (50-90 % 20R)*'*' -lo5 The reaction with stabilized ylides has been explored, mainly with the aim of producing the side-chain of the cardenolides. Reaction of 3,21-diacetoxypregn-5-en-20-one with diethyl cyanomethylenephosphonate gives a high yield of the E-isomer, which can be converted by saponification into the lact~ne.'~~-'~~ 'OoaT.Kametani, M. Tsubuki, and H. Nemoto, J. Chem. Soc., Perkin I, 1981, 3077; T.Kametani, M. Tsubuki, and H. Nemoto, Tetrahedron Lett., 1981, 22, 2373. J. P. Schmit, M. Piraux, and J. F. Pilette, J. Org. Chem., 1975, 40,1586. lo' T. C. McMorris and S. R. Schow, J. Org. Chem., 1976,41, 3759. lo3 S. R. %how and T. C. McMorris, J. Org. Chem., 1979, 44, 3760. lo4 A. Furst, L. Labler, and W. Meier, Helv. Chim. Acra, 1982, 65, 1499. lo' W. R. Nes, J. Am. Chem. Soc., 1978, 100, 999. G. R. Lenz and J. A. Schulz, J. Org. Chem., 1978,43, 2334. lo' G. R. Pettit, C. L. Herald, and J. P. Yardley, J. Org. Chem.. 1970, 35, 1389. 91 Stereoselective Synthesis of Steroid Side-chuins 0011 57% ; 86" Scheme 21 Redpath and Zeelen The reaction with the triethylphosphonoacetate was reported to proceed in high yield.'" Some authors, however, reported problems in repeating this work.'06,109 OCOMe An interesting example of an intramolecular Wittig cyclization was reported by Nickisch, Klose, and Bohlmann' lo (Scheme 22) using ketenylidentri-phenylphosphoran.The reaction proceeds with a remarkable selectivity. Reactionsof 21-Toluene-p-sulphonates.-The sulphonylox y-group can be displaced by the anion of diethylmalonate,' '' or of a~etylides'~~*'' -'l4 or sulph~nes,'~~ and by cuprate Grignard reagents. '14'vb The 22-position can be activated by conversion of the toluene-p-sulphonate via bromide into sulphone. The anion can then be generated and used for coupling with ele~trophiles.~~ Similar approaches '08 W. Fritsch, U. Stache, and H.Rushig, Liebigs Ann, Chem., 1966, 699, 195. '09 E. Yoshii and K. Ozaki, Chem. Pharm. Bull., 1972, 20, 1585. 'lo K. Nickisch, W. Klose, and F. Bohlmann, Chem. Ber., 1980, 113, 2038. ''I R. Hayatsu, Chem. Pharm. Bull., 1957, 5,452. '" J. J. Partridge, S. Faber, and M. R. Uskokovic, Helr. Chim. Acta, 1974, 57, 764. 'I3 Y. Fujimoto, M. Morisaki, and N. Ikekawa, J. Chem. Sor., Perkin 1, 1975, 2302. '14 E. Steiner and C. Djerassi, Helv. Chim. Acta, 1977, 60,475. B. Lythgoe, D. A. Roberts, and I. Waterhouse, J. Chem. SOC., Perkin I, 1977, 2608. G. A. Leyes and W. H. Okamura, J. Am. Chem. Soc., 1982, 104, 6099. 93 Stereoselective Synthesis of Steroid Side-chuins 'have been described using the 24-toluene-p-sulphonates' and 24-sulphones.'16*' l7 11 TI Scheme 23 Reactions of 20Xarboxaldehydes.---With 3~-hydroxypregn-5-ene-20-carboxalde-hyde available by synthesis and by degradation of stigmasterol, it is often used as a starting material.It has the disadvantage that isomerization at the 20-position can The Wittig reaction with non-stabilized ylides can be made to yield either predominantly the E-isomer or the Z-isomer at the 22(23) double bond, depending on the choice of reaction condition^.^^^"^-'^^ This is a common feature of Wittig reactions of relatively unhindered aldehydes. The reaction with stabilized ylides yields, as expected, the Z-isomers"9.'22-123 (Scheme 24). An alternative route to 2-alkenes proceeds uiu addition of alkylsulphones followed by re-duction.7a,3 20.3 5,3 6,124 The stereochemistry of addition reactions to these 22(23) double bonds is strongly dependent on substituents present in the side-chain.An example is the 'I5 Y. Kobayashi. T. Taguchi, T. Terada, .I.Oshida, M. Morisaka, and N. Ikekawa, Trtruhrdron Lett.. 1979, 2023. 'Ih Y. Kobayashi, T. Taguchi, N. Kanuma, N. Ikekawa, and J. Oshida, J. Chrni Soc., Chem. Commun., 1980, 459. 117 Y. Kobayashi, T. Taguchi, N. Kanuma, N. Ikekawa, and J. Oshida, Tetruhedron Lett.. 1981.22, 4309. 'I8 D. H. R. Barton, T. Shiori, and D. A. Widdowson. J. Chem. Soc., Chem. Commun., 1970. 939. R. F. N. Hutchins, M. J. Thompson, and J. A. Svoboda, Steroids, 1970, 15, 113. lZo R. W. Lang and C. Djerassi, J. Org. Chem., 1982, 47, 625. W. G.Salmond, M. A. Barts, and J. L. Havens, J. Org. Cham., 1978, 43. 790. 122 G. D. Anderson, T. J. Powers. C. Djerassi, J. Fayos, and I. C'lardy, J. Am. Chrm. So(., 1975, 97, 389. 123 P. H. Le, M. W. Preus, and T. C. McMorris, J. Org. Chem., 1982, 47, 2163. 12' P. J. Kocienski, B. Lythgoe, and D. A. Roberts, J. Chem. Soc.. Perkin Trans. I, 1978. 834. 94 Redpath and Zeelen H H ,c=o tl OsO, hydroxylation of E-22(23) double bonds where the ratio between the 22aF ,23pF- and 22pF ,23aF-diols formed may vary between 70: 30 and 15:85 depending on the substituents of the ~ide-chain.'~~- Reaction of E-cholest-12' 22-en-24-ones with alkaline hydrogen peroxide3*.' 28*129 or with dime t h yloxo- sulphonium methylide'22 gave almost exclusively the 22pF ,23aF-oxide or 22pF ,23aF-methylene derivatives.Reactions of 20-carboxaldehydes with alkyl Grignard reagents, preferably in polar solvents,' 30 -132 or with dimethylsulphonium methylide' 25 favour the formation of 22aF alcohols. Addition of ~inylic,'~~-'~~ and even more of the sterically less demanding acetylenic,' 1,85,137*138 reagents tends to be less stereoselective. 125 M. Ishiguro, H. Saito, A. Sakamoto, and N. Ikekawa, Chem. Pharm. Bull., 1978, 26, 3715. 126 M. Hirayama, K. Gamoh, and N. Ikekawa, J. Am. Chem. SOC., 1982, 104, 3735. 127 M. J. Thompson, W. J. Meudt, N. B. Mandava, S. R. Duthy, W. R. Lusby, and D. W. Spaulding, Steroids, 1982, 39, 89. 128 G. R. Weihe and T. C. McMorris, J. Org. Chem., 1978, 43, 3942.129 E. Glotter, M. Zviely, and I. Kirson, J. Chem. Res. (S), 1982, 32; (M), 1982, 373. 130 J. P. Poyser and G. Ourisson, J. Chem. SOC., Perkin Trans. I, 1974, 2061. 131 Y. Hirano and C. Djerassi, J. Org. Chem., 1982,47, 2420. 132 M. Ishiguro, A. Akaiwa, Y. Fujirnoto, S. Sato, and N. Ikekawa, Tetrahedron Lett., 1979, 763. 133 T. A. Narwid, K. E. Cooney, and M. R. Uskokovic, Helv. Chim. Acta, 1974, 57, 771. 134 R. D. Walkup, G. D. Anderson, and C. Djerassi, Tetrahedron Lett., 1979, 767. 135 S. Fung and J. B. Siddall, J. Am. Chem. SOC.,1980, 102, 6581. 136 N. Ikekawa, Y. Hirano, M. Ishiguro, J. Oshida, T. Eguchi, and S. Miyasaka, Chem. Pharm. Bull., 1980, 28, 2852. 137 M.Ishiguro, S. Takatsuto, M. Morisaka, and N. Ikekawa, J. Chem.SOC.,Chem. Commun., 1980,962. 138 T. B. Kline and G. D. Prestwich, Tetrahedron Lett., 1982, 23, 3043. 95 Stereoselective Synthesis of Steroid Side-chains H HhYH222-0 97;: Scheme 25 Chirality Transfer.-In the flexible side-chains, diastereoselectivity is unimportant unless one uses reactions with a transition-state which freezes part of that chain. This is the concept of chirality transfer. We have already discussed Pd-catalysed 1,3-chirality-transfer used for the synthesis of 24-hydroxycholestero1.85 Epoxidation of allylic alcohols also proceeds via rigid transition-states resulting in high stereoselectivity for the formation of the threo isomer in the case of 1,3-dialkylsubstituted cis-ally1 alcohols, or erythro isomers in the case of 1,2-dialkyl-substituted ally1 alcohols.' 39 This principle was used in two syntheses of brassinolide' 35*137 and for the stereoselective syntheses of 25,26-dihydroxy-ch~lesterols~~(Scheme 26).The CIaisen rearrangement proceeds tlia a chair-like 6-membered transition- state. For the 22-alcohols the stereochemistry at C-24 in the product is determined by the preference of the bulky steroid nucleus to occupy the equatorial position, by the configuration at C-22, and the stereochemistry of the double bond at C-23. Claisen rearrangement with trimethyl orthoacetate yields one product.' ','31 Rearrangement with orthopropionates yields products homogeneous at C-24 but epimeric at the 25-po~ition~'~'~~~'~~"~'~~(Scheme 27). This contrasts with the Claisen rearrangement using 1-methoxy-1-(dimethy1amino)prop-1-ene,which was 13" A.Y. L. Shu and C. Djerassi, Tetrahedron Lett., 1981, 22, 4627. 13' B. E. Rossiter, T. R. Verhoeven, and K. B. Sharpless, Tetrahedron Lett., 1979, 4733. 14' M. A. Gilhooly, D. S. Morris, and D. H. Williams, J. Chem. Soc., Perkin Trans. I, 1982, 211 1. Redpath and Zeelen H t-BuOOH VO(MeCOCIiCOMe)2 Tf{PO 85% 70% Scheme 26 COOMe (ref. 11) 62% OMe 6Me 63% Scheme 27 Stereoselective Synthesis of Steroid Side-chains mentioned earlier and proceeds stereoselectively both for the 24-and 25-position~37,38,141144-The Claisen rearrangement has also been used to transfer chirality from the 24-01s back to the 22-position for the stereoselective synthesis of both 22R- and 22s-22-rnethylchole~terol.~~ The nature of the Carroll rearrangement of a /?-ketoacetate of 20S-6p-methoxy-20-ethenyl-3a,5-cyclo-5a-pregnan-20-01remains unspecified but yielded a 1:2 mixture of cis and trans isomers.'33 It was, however, successfully applied with E-6~-methoxy-3a,5-cyclo-5a-pregn-17(20)-en-16a-01.'~~ An oxy-Cope rearrangement was used for the stereoselective synthesis of 3p-(tetrahydropyran-2-yl)oxychola-5,23-dien-16-one.46 An interesting new development is the use of 1,3-dipolar addition reactions. 14' 141 W. Sucrow, P. P. Caldeira, and M. Slopianka, Chem. Ber., 1973, 106, 2236. 14* W. Sucrow, M. Slopianka, and P. P. Caldeira, Chem. Ber., 1975, 108, 1101. 143 W. Sucrow and M.Slopianka, Chem. Bet-., 1975, 108, 3721. 144 H. W. Kircher and F. U. Rosenstein, J. Org. Chem., 1982, 47, 1722. 145 M. Tanabe and K. Hayashi, J. Am. Chem. SOC.. 1980, 102, 862. M. Koreeda, Y. Tanaka, and A. Schwartz, J. Org. Chem., 1980, 45, 1174. 14' J. J. Partridge, N. K. Chadha, A. D. Batcho, and M. R. Uskokovic, Abstr. Papers. Am. Chem. SOC., 1981, 182 meeting, p. 35. 98

ISSN:0306-0012    

DOI:10.1039/CS9831200075

出版商:RSC    

年代:1983

数据来源: RSC

摘要:

INDEXES Volume 12, 1983 The indexes in this issue cover Volumes 1-12 (Figures in bold type refer to the volume number) Index INDEX OF AUTHORS Aarons, L. J., 5, 359 Ackroyd, J., 11, 321 Ager, D. J., 11, 493 Ahluwalia, J. C., 2, 203 Allen, N. S., 4, 533 Angyal, S. J., 9, 415 Ambroz, H. B., 8, 353 Atkinson, D., 8, 475 Baker, A. D., 1, 355 Barber, B. E., 9, 143 Bartle, K. D., 10, 113 Bartlett, P. D., 5, 149 Baxendale, J. H., 7, 235 Beattie, I. R., 4, 107 Bell. R. P., 3, 513 Belson, D. J., 11, 41 Bentley, P. H., 2, 29 Berkoff, C. E., 3, 273 Bird, C. L., 10, 49 Bird, C. W., 3, 309 Blandamer, M. J., 4, 55 Blundell, T. L., 6, 139 Boelens, H., 7, 167 Bradshaw, T. K., 6, 43 Braterman, P.S., 2, 271 Breslow, R., 1, 553 Brown, D. H., 9, 217 Brown, I. D., 7, 359 Brown, K. S., jun., 4, 263 Brundle, C. R., 1, 355 Buchanan, G. L., 3, 41 Burdett, J. K., 3, 293; 7, 507 Burgess, J., 4, 55 Burnett, M. G., 12, 267 Burrows, H. D., 3, 139 Burtles, S. w,,7, 201 Butterworth, K. R., 7, 185 Cadogan, J. I. G., 3, 87 Carabine, M. D., 1, 41 1 Cardin, D. J., 2, 99 Carless, H. A. J., 1, 465 Casellato, U., 8, 199 Cetinkaya. B., 2, 99 Chamberlain, J., 4, 569 Chatt, J., I, 121 Chesters, J. K., 10, 270 Chivers, T., 2, 233 Clark, G. M., 5, 269 Collins, C. J., 4, 251 Colvin, E. W., 7, 15 Connor, J. N. L., 5, 125 Corfield, G. C., 1, 523 Cornforth, J. W., 2, 1 Cotton, F. A., 4, 27; 12,35 Coulson, E.H., 1, 495 Cowan, J. M., 8, 419 Cox, B. G., 9, 381 Coyle, J. D., 1, 465; 3, 329; 4, 523 Cragg, G. M. L., 6, 393 Cramer, R. D., 3, 273 Crammer, B., 6, 431 Cross, R. J., 2, 271; 9, 185 Curthoys, G., 8, 475 Dack, M. R. J.. 4, 21 1 Dainton, F. S., 4, 323 Dalton, H., 8, 297 Davies, D. I., 8, 171 de Rijke, D., 7, 167 de Silva, A. P., 10, 181 de Valois, P. J., 7, 167 Dickinson, L. C., 12, 387 Dobson, J. C., 5, 79 Dowle, M. D., 8, 171 Doyle, M. J., 2, 99 Drummond, I, 2, 233 Dunkin, 1. R., 9, 1 Duxbury, G., 12,453 Elliott, M., 7, 473 Emsley, J., 9, 91 Eschenmoser, A., 5, 377 Evans, D. A., 2, 75 Evans, J., 10, 159 Fenby, D. V., 3, 193 Fenton, D. E., 6, 325; 8, I99 Ferguson, L.N., 4, 289 Fisher, L. R., 6, 25 Fleming, I., 10, 83 Flygare, W. H., 6, 109 Forage, A. J., 8, 309 Fox, M. F., 9, 143 Frazer, M. J., 11, 171 Fry, A., I, 163 Funk, R. L., 9, 41 Garson, M. J., 8, 539 Georghiou, P. E., 6, 83 Gheorghiu, M. D., 10, 289 Gibson, K. H., 6, 489 Gilbert, J., 10, 255 Gilchrist. T. L., 12, 53 Gillespie, R. J., 8, 315 Goodings, E. P., 5, 95 Gorman, A. A., 10, 205 Gray, B. F., 5, 359 Grecn, C. L., 2, 75 Greenhill, J. V., 6, 277 Greenwood, N. N., 3, 23 1 Grey Morgan, C., 8, 367 Grice, R., 11, 1 Griffiths, J., I, 481 Grimshaw, J., 10, 181 Grossert, J. S., 1, 1 Groves, J. K., 1, 73 Guilford, H., 2, 249 Gutteridge, N. J. A., 1, 38 1 Haines, R. J., 4, 155 Hall, G.G., 2, 21 Hall, L. D., 4, 401 Hall, T. W., 5, 431 Halliwell, H. F., 3, 373 Hamdan, I. Y., 8, 143 Hamer, G., 8, 143 Harmony, M. D., 1, 211 Harris, K. R., 5, 215 Harris, R. K., 5, 1 Harrison, L. G., 10, 491 Hartley, F. R., 2, 163 Hartshorn, S. R., 3, 167 Hathway, D. E., 9, 63, 241 Hayward, R. C., 12, 285 Heelis, P. F., 11, 15 Henderson. J. W., 2, 397 Hepler, L. G., 3, 193 Hilburn, M. E., 8, 63 Hinchliffe, A., 5, 79 Holbrook, K. A., 12, 163 Holland, H. L., 10, 435; 11, 37 Holm, R. H., 10, 455 Hore, P. J., 8, 29 Horton, E. W., 4, 589 Hudson, M. F., 4, 363 Huntress, W. T. jun.. 6, 295 Hutchinson, D. W., 6, 43 Ibers, J. A., 11, 57 Ikan, R., 6, 431 Isaacs, N.S., 5, 181 Isbell, H. S., 3, 1 Jaffk, H. H., 5, 165 James, A. M., 8, 389 Jamieson, A. M., 2, 325 Janes, N. F., 7, 473 Jencks, W. P., 10, 345 Jenkins, J. A., 6, 139 Johnson, A. W., 4, 1; 9, 125 Johnson, S. P., 5, 441 Johnstone, A. H., 7, 317; 9, 365 Jones, J. R., 10, 329 Josh, C. G., 8, 29 Jotham, R. W., 2,457 Kalyanasundaram, K., 7,453Keenan, A. G., 8, 259 Kemp, T. J., 3, 139; 8, 353 Kennedy, J. F., 2, 355: 8, 221 Kennewell, P. D., 4, 189; 9, 477 Kenny, A. W., 4, 90 King, G. A. M., 7, 297 Kirby, G. W., 6, 1 Kitaigorodsky, A. I., 7, 133 Koch, K. R., 6, 393 Kolar, G. F., 9, 241 Korpela, T., 12, 309 Kresge, A. J., 2, 475 Krishnaji, 7, 219 Kroto, H., 11, 435 Kruger, H., 11, 227 Kuhn, A.T., 10, 49 Lappert, M. F., 2, 99 Lee, M. L., 10, 113 Lee-Ruff, E., 6, 195 Leigh, G. J., 1, 121; 4, 155 Lemieux, R. U., 7, 423 Leznoff, C. C., 3, 65 Lindberg, B., 10, 409 Lindsay, D. G., 10, 233 Lindoy, L. F., 4, 421 Linford, R. G., 1, 445 Lipscomb, W. N., 1,319 Liu, M. T. H., 11, 127 Lynch, J. M., 3, 309 Lythgoe, B., 9, 449 Makela, M. J., 12, 309 McCleverty, J. A., 12, 331 McKean, D. C., 7, 399 McKellar, J. F., 4, 533 McKervey, M. A., 3, 479 Mackie, R. K., 3, 87 McLauchlan, K. A., 8, 29 McNab, H., 7, 345 Maitland, G. C., 2, 181 Maitlis, P. M., 10, 1 Manning, P. G., 5, 233 Maret, A. R., 2, 325 Maslowsky, E., 9, 25 Mason, R., 1, 431 Mayo, B.C., 2, 49 Meadowcroft, A. E., 4, 99 Menger, H. W., 2,415 Midgley, D., 4, 549 Millen, D. J., 5, 253 Mills, R., 5, 215 Moore, D. S., 12, 415 Moore, H. W., 2, 415;10, 289 Morley, R., 5, 269 Morris, D. G., 11, 397 Morris, J. H., 6, 173 Muetterties, E. L., 11, 283 Mulheirn, L. F., 1, 259 Munn, A., 4, 87 Murphy, W. S., 12, 213 Newman, J. F., 4, 77 Nightingale, W. H., 7, 195 Norman, R. 0.C., 8, 1 North, A. M., 1, 49 Oakenfull, D. G., 6, 25 Overton, K. H., 8, 447 Page, M. I., 2, 295 Parthasarathy, R., 12, 361 Pclter, A,, 11, 191 Perkins, P. G., 6, 173 Pickford, C. J., 10, 245 Pletcher, D., 4, 471 Poliakoff, M., 3, 293; 7, 527 Prakash, V., 7, 219 Pratt, A.C., 6, 63 Puddephatt, R. J., 12, 99 Ramm, P. J., 1, 259 Rao, C. N. R., 5, 297; 12, 361 Rao, K. J., 12, 361 Index Ratledge, C., 8, 283 Rattee, 1. D., 1, 145 Redl, G., 3, 273 Redpath, J., 12, 75 Richards, D. H., 6, 235 Ritch, J. B., jun., 5, 452 Roberts, M. W., 6, 373 Robinson, F. A., 5, 317 Robinson, S. D., 12, 415 Roche, M., 5, 165 Rodgers, M. A. J., 7, 235 Rose. A. E. A., 6, 173 Rouvray, I).H., 3, 355 Rowlinson, J. S., 7, 329;12, 251 Sanders, J. K. M., 6, 467 Sarma, T. S., 2, 203 Satchel], D. P. N., 4, 231; 6, 345 Satchel], R. S., 4, 231 Scheinmann, F., If, 321 Schlegel, W., 7, 177 Scriven, E. F. V., 12, 129 Self, R., 10, 255 Senthilnathan, V. P., 5, 297 Shorter, J., 7, 1 Simpson, T.J., 4, 497 Singh, S., 5, 297 Slorach, S. A., 10, 280 Smith, E. B., 2, 181 Smith, K., 3, 443 Smith, K. M., 4, 363 Smith, W. E., 6, 173; 9,21 7 Sncll, K. D., S, 259 Stacey, M., 2, 145 Staunton, J., 8, 539 Stevens, M. F. G., 7, 377 Stoddart, J. Fraser, 8, 85 Stokes, R. H., 11, 257 Strachan, A. N., 11, 41 Suckling, C. J., 3, 387 Suckling, K. E., 3, 387 Sutherland, J. K., 9, 265 Sutherland, R. G., 9,241 Sutton, D., 4, 443 Swan, J. S., 7, 201 Swindells, R., 7, 212 Symons, M. C. R., 5, 337; 12, 1, 387 Index Takken, H. J., 7, 167 Taylor, J. B., 4, 189; 9, 477 Taylor, S. E., 10, 329 Theobald, D. W., 5, 203 Thomas, T. W., 1, 99 Thompson, M., 1, 355 Thornber, C.W., 8, 563 Tincknell, R. C., 5, 463 Toennies, J. P., 3, 407 Tolman, C. A., 1, 337 Trost, B. M., 11, 141 Truax, D. R., 5,411 Twitchett, H. J., 3, 209 Tyman, J. H. P., 8, 499 Underhill, A. E., 1, 99; 9,429 van Dort, J. M., 7, 167 van der Linde, L. M., 7, 167 Varvoglis, A., 10, 377 Vaughan, K., 7, 377 Vidali, M., 8, 199 Vigato, P. A., 8, 199 Vollhardt, K. P. C., 9, 41 Wain, R. L., 6, 261 Walker, E. R. H., 5, 23 Walker, I. C., 3, 467 Waltz, W. L., 1, 241 Ward, I. M., 3, 231 Ward, R. S., 11, 75 Watkins, D. M., 9, 429 Wattanasin, S., 12, 213 White, A. J., 3, 17 Whitfield, R. C., 1, 27 Wieser, H., 5, 411 Wiesner, K., 6, 413 Williams, G., 7, 89 Williams, R.J. P., 9, 281, 325 Wilson, A. D., 7,265 Wise, S. A., 10, 113 Yoffe, A. D., 5, 51 Zeelen, F. J., 12, 75 Index INDEX OF TITLES Abiotic receptors, 12, 285 Absorption bands in the spectra of stars, a crystal field approach, 5,233 Acidity of solid surfaces, 8,475 Across the living barrier, 6, 325 Acylation and alkylation catalysts, 4-dialkylaminopyridines, super,12, 129 -by ketens and isocyanates, a mechanistic comparison, 4, 23 1 Acylation, Friedel-Crafts, of alkenes, 1, 73 Adamantane rearrangements, 3, 379 Affinity chromatography, chemical aspects of, 3, 249 Alcohols and amines, conformational analysis of, 5, 411 Alkali-metal complexes in aqueoussolution, 4, 549 Alkaloids, aconite, synthesis of, 6, 413 Alkenes, the Friedel-Crafts acylationof, 1, 73 Aluminium phosphates, the chemistry and binding properties of, 6, 173 Amines and alcohols, conformational analysis of, 5, 411 Analysis of trace constituents of the diet, organic and inorganic,10, 245, 255 Analytical methods, modern, for environmental polycyclic aromatic compounds, 10, 113 Anionic cyclization of phenols, 12, 21 3 Aphids and scale insects, their chemis- try, 4, 263 Application of electrochemical tech-niques to the study of homogeneous chemical reactions, 4, 471 Applications of e.s.r.spectroscopy to kinetics and mechanism in organic chemistry, 8, 1 Application of research findings to the development of commercial flavourings, 7, 177 Aqueous mixtures, kinetics of reactions in, 4, 55 Aqueous solution, micelles in, 6, 25 Aryl cations-new light on old inter- mediates, 8, 353 ~ halides, photochemistry and photocyclization of, 10, 181 Aryldiazonium cations, co-ordination chemistry of, 4,443 Aryliodine(II1) dicarboxylates, 10, 377 Atmosphere, interactions in, of drop-lets and gases, 1, 411 Autocatalysis, 7, 297 Azidoquinones and related com-pounds, chemistry of, 2,415 Azobenzene and its derivatives, photo- chemistry of, 1,481 Bile pigments, 4, 363 Binding of heavy metals to pro-teins, 6, 139 Binding properties and chemistry of aluminium phosphates, 6, 173 Biological surfaces, molecular aspects of, 8, 389 Biomimetic chemistry, 1, 553 Biosynthesis of sterols, 1, 259 Biosynthetic products from arachidonic acid, 6, 489 -studies, carbon-13 nuclear magnetic resonance in, 4,497 Bis(diphen ylphosphino)methane, chemistry of, 12,99 Blood groups, human, and carbo-hydrate chemistry, 7,423 Bond strengths, CH, in simple organic compounds: effects of conformation and substitution, 7, 399 -valences-a simple structural model for inorganic chemis-try, 7, 359 Boron reagents, carbon-carbon bond formation involving, 11, 191 Bredt’s rule, 3, 41 Brnnsted relation-recent develop-ments, 2,475 Butadiene, polymerization and co-polymerization of, 6, 235 Calciferols, hormonal: chemistry of “vitamin” D, 6, 83 Calorimetric investigations of hydro- gen bond and charge transfer com- plexes, 3, 193 Cancer and chemicals, 4, 289 Carbohydrate chemistry and human blood groups, 7,423 Carbohydrate-directed macromole-cules, transition-metal oxide chelates of, 8, 221 Carbohydrate-protein complexes, gly- coproteins, and proteoglycans, of Index human tissues, chemical aspectsof, 2, 355 Carbohydrates to enzyme analogues, 8, 85 Carbon-carbon bond formation in-volving boron reagents, 11, 191 Carbon- 13 nuclear magnetic resonance in biosynthetic studies, 4,497 Carbonium ions, carbanions, and radi- cals, chirality in, 2, 397 Carbonyl clusters, metal, relationship with supported metal cata-lysts, 10, 159 compounds, photochemistry of, 1, 465 ___ equivalents, silicon-containing,11,493 __ group transpositions, 11, 397 Carcinogens, chemical, mechanisms of reaction with nucleic acid, 9, 241 Catalysis and surface chemistry, new perspectives, 6, 373 Catalysis, homogeneous, and or-ganometallic chemistry, the 16 and 18 electron rule in, 1, 337 __ of the olefin metathesis reaction, 4, 155 Catalysts, supported metal, relationship with metal carbonylclusters, 10, 159 CENTENARY LECTURE.Biomimetic chemistry, 1, 553 CENTENARY LECTURE. Cyclopen- tanoids: a challange for new methodology, 11, 141 CENTENARY Hydrocarbon re- LECTURE. . actions at metal centres, 11, 283 CENTENARY Light scattering LECTURE. in pure liquids and solutions, 6, 109 CENTENARY Metal clusters in LECTURE. biology, 10,455 CENTENARY LECTURE. Quadruple bonds and other multiple metal to metal bonds, 4, 27 CENTENARYLECTURE.Reactivities of carbon disulphide, carbon dioxidc, and carbonyl sulphide towards some transition-metal systems, 1 I, 57 CENTENARY Rotationally and LECTURE.vibrationally inelastic scattering of molecules, 3, 407 CENTENARY Sytematic devel- LECTURE. opment of strategy in the synthesis of polycyclic polysubstituted natural products: the aconite alkaloids, 6, 413 CENTENARY LECTURE. Three-dimensional structures and chemical mechanism of enzymes, 1, 319 Charge transfer and hydrogen bond complexes, calorimetric in-vestigations of, 3, 193 Chemical applications of advances in Fourier transform spectroscopy,4, 569 aspects of affinity chro-ma tograp hy , 2, 249 ~~ of glycoproteins, proteo- glycans, and carbohydrate-proteincomplexes of human tissues, 2, 355 --education research: facts, findings, and consequences, 9, 365 -interpretations of molecular wave- functions, 5, 79 models of enzymic trans-imination, 12, 309 Chemically-induced dynamic electron polarization (CIDEP), role in chem- istry, 8, 29 Chemicals in rodent control, 1, 381 __-which control plant growth,6, 261 Chemistry and binding properties of aluminium phosphates, 6, 173 CHEMISTRY AND FLAVOUR I Molecular Structure and Organoleptic Quality, 7, 167 I1 Application of Research Findings to the Development of Commer-cia1 Flavourings, 7, 177 I11 Safety Evaluation of Natural and Syntheic Flavourings, 7, 185 IV The Influencc of Legislation on Research in Flavour Chemistry,7, 195 V The Development of Flavour in Potable Spirits, 7, 201 VI The Influence of Flavour Chemistry on Consumer Accept- ance, 7,212 ~ and the new industrial revolution, 5, 317 ~-,--a topological subject, 2, 457 of aphids and scale insects, 4, 263 of azidoquinones and related corn- pounds, 2, 415 ,of dental cements, 7, 265 of dyeing, 1, 145 __ of the gold drugs used in the treat- ment of rheumatoid arthritis, 9, 217 ___ of homonuclear sulphur spccies, 2,233 -of long-chain phenols of non-isoprenoid origin, 8, 499 -of the production of organic iso- cyanates, 3, 209 -of transition-metal carbene com- plexes and their role as reaction inter- mediates, 2, 99 of “vitamin” D: the hormonal cal- ciferols, 6, 83 -, some considerations on the philosophy of, 5, 203 Chirality in carbonium ions, car-banions, and radicals, 2, 397 Chlorophyll chemistry, n.m.r.spectral change as a probe, 6,467Chromatography, affinity, chemical as- pects of, 2, 249 cis-and trans-Effects of ligands, 2, 163 Clathrates and molecular inclusion phenomena, 7, 65 Collisional transfer of rotational energy and spectral lineshapes, 7, 219 Compartmental ligands: routes to homo-and hetero-dinuclear com-plexes, 8, 199 Complex formation between sugars and metal cations, 9,415hydride reducing agents, the func- tional group selectivity of, 5, 23 Complexes, alkali-metal, in aqueous solution, 4, 549 homo-and hetero-dinuclear, routes via compartmental ligands, 8, 199 -, 1-D metallic, 9,429 -, square-planar, isomerization mechanisms of, 9, 185 Computer resolution of overlappingelectronic absorption bands, 9, 143 Conductivity and superconductivity in polymers, 5, 95 Conformation and substitution, effects of, on individual CH bond strengths in simple organic compounds, 7, 399 -of rings and neighbouring group effects, development of Haworth’s concepts of, 3, 1Conformational analysis of some alco- hols and amines: a comparison of molecular orbital theory, rotational and vibrational spectroscopy, 5, 41 1 -studies on small molecules, 1,293 Contribution of ion-pairing to ‘memory effects’, 4, 251 Contributions of pulse radiolysis to chemistry, 7, 235 Index Conversion of ammonium cyanate into urea-a saga in reaction mech-anisms, 7, 1Co-ordination chemistry of aryl-diazonium cations: aryldiazenato(arylazo) complexes of transition metals, and the aryldiazenato-nitrosyl analogy, 4,433Corrin synthesis, post-B, problems in, 5, 377 Crystal field approach to absorption bands in the spectra of stars, 5, 233 Crystals and molecules, organic, non- bonded interactions of atoms in, 7, 133 Current aspects of unimolecular reac-tions, 12, 163 Cyanocobalt(Ir1) complexes, the syn- thesis of mononuclear, 12, 267 Cyanoketenes: synthesis and cyclo-additions, 10, 289 Cyclization, initiation of, using3-methylcyclohex-2-enone deriva-tives, 9, 265 of phenols, anionic, 12, 213 Cyclopentanoids: a challange for new methodology, 11, 141 Cyclopolymerization, 1, 523 Dental cements, chemistry of, 7, 265 Development of flavour in potable spir- its, 7, 201 4-Dialkylaminopyridines: super acyla- tion and alkylation catalysts, 12, 129 Diazirines, the thermolysis and photo- lysis of, 11, 127 Dielectric relaxation in polymer solu- tions, 1, 49 Diffusion in liquids, the effect of iso- topic substitution on, 5, 215 Difluoroamino-radical, gas-phasekinetics of, 3, 17 Droplets and gases, interactions in the atmosphere of, 1, 41 1 Drug design, isosterism and molecular modification in, 8, 563 _~ _, quantitative, 3, 273 Dyeing, chemistry of, 1, 145 Echinoderms, 1, 1Education, chemical, a reassessment of research in, 1, 27 -~ __ , review of research and de- velopment in the U.K., 1972-1976, 7, 317 Effect of isotopic substitution on diffusion in liquids, 5, 215 511 Index Electrochemical techniques, applica-tion of to study of homogeneous chemical reactions, 4,471Electron as a chemical entity, 4, 323 __ scattering spectroscopy, thresh- old, 3, 467 -spectroscopy, 1, 355 Electronic absorption bands, overlap- ping, computer resolution of, 9, 143 -properties of some chain and layer compounds, 5, 51 __ transitions, vibrational intensities in, 5, 165 Electrons, solvated, in solutions of metals, 5, 337 Electron spin resonance of hae-moglobin and myoglobin, 12, 387 Electrophilic aromatic substitutions, non-conventional, and related reac-tions, 3, 167 C-nitroso-compounds, 6, 1Elimination reactions, isotope effect studies of, 1, 163 Enaminones, 6, 277 Energetics of neighbouring group participation, 2, 295 Enumeration methods for isomers, 3, 355 Environmental lead in perspec-tive, 8, 63 polycyclic aromatic compounds, modern analytical methods for, 10, 113 ___ protection in the distribution of hazardous chemicals, 4, 99 -regulation: an international view, 5, 431 Enzyme analogues from carbo-hydrates, 8, 85 Enzymes, immobilized, 6, 215 -in organic synthesis, 3, 387 -----, the logic of working with, 2, I -, three-dimensional structures and chemical mechanisms of, 1, 319 Enzymic reactions, stereochemical choice in, 8, 447 E.s.r.spectroscopy, applications to ki- netics and mechanism in organic chemistry, 8, 1Experimental studies on the structure of aqueous solutions of hydrophobic solutes, 2, 203 FARADAY The electron as aLECTURE. chemical entity, 4, 323 FARADAY The molecular the- LECTURE. ory of small systems, 12, 251 Fast reactions, techniques for the kinetic study of, 11, 227 Fats grown from wastes, 8, 283 Fe(CO),, 7, 527 5-Substituted pyrimidine nucleosides and nucleotides, 6, 43 Fixation, of nitrogen, 1, 121 Flavins (isoalloxazines), the photo-physical and photochemical proper- ties of, 11, 15 Forces between simple molecules, 2,18 1 Foreign compounds in mammals, im- portance of non-enzymic chemical reaction processes to the rate of, 9, 63 Formation of hydrocarbons by micro- organisms, 3, 309 Fourier transform spectroscopy, chem- ical applications of advances in, 4,569 Four-membered rings and reaction mechanisms, 5, 149 FriedelLCrafts acylation of alkenes, 1, 73 Functional group selectivity of complex hydride reducing agents, 5, 23 Gas-phase kinetics of the difluoroamino-radical, 3, 17 Gases, and droplets, interactions in the atmosphere of, 1,411Glass transition: salient facts and the- oretical models, 12, 361 Glycoproteins, proteoglycans, and carbohydrate-protein complexes of human tissues, chemical aspects 0f, 2, 355 Gold drugs used in the treatment of rheumatoid arthritis, chemistry of, 9, 217 Growth of computational quantum chemistry from 1950 to 1971, 2, 21 Haemoglobin and myoglobin, electron spin resonance of, 12, 387 Handling toxic chemicals--environ-mental considerations, 4, 77 HAWORTH MEMORIAL LECTURE.The consequences of some projectsinitiated by Sir Norman Haworth, 2, 145 HAWORTH MEMORIAL TheLECTURE. Haworth-Hudson controversy and the development of Haworth’s con- cepts of ring conformation and of neighbouring group effects, 3, 1 HAWORTH MEMORIAL LECTURE. Hu- man blood groups and carbohydrate chemistry, 7, 507 HAWORTH LECTURE.MEMORIAL Struc-tural studies of polysaccharides,10,409 Hazards in the chemical industry-risk management and insurance, 8,419 Health hazards to workers from indus- trial chemicals, 4, 82 High resolution laser spectroscopy,12,453 Homogeneous catalysis, and or-ganometallic chemistry, the 16 and 18 electron rule in, 1, 337 -chemical reactions, application of electrochemical techniques to the study of, 4, 471 Human blood groups and carbo-hydrate chemistry, 7, 423 Hydrido complexes of the transition metals, 12,415 Hydrocarbon formation by micro-organisms, 3, 309 reactions at metal centres, 11, 283 Hydrogen bond and charge transfer complexes, calorimetric in-vestigations of, 3, 193 -bonded liquids, thermodynamics of, 11, 257 -bonding, very strong, 9, 91 __ isotope effects, kinetic, recent ad- vances in the study of, 3, 513 Hydrophobic solutes, experimentalstudies on the structure of aqueous solutions of, 2, 203 Imines, photochemistry of, 6,63 Immobilized enzymes, 6, 215 Importance of (non-enzymic) chemical reaction processes to the fate of for- eign compounds in mammals, 9,63 ~ ~-solvent internal pressure and cohesion to solution phenomena, 4, 21 1 Inclusion phenomena, molecular, and clathra tes, 7, 65 Individual CH bond strengths in simple organic compounds: effects of con- formation and substitution, 7, 399 Industry, chemical, hazards in: risk management and insurance, 8,4 I9 Influence of flavour chemistry on con- sumer acceptance, 7,212 __-legislation on research in flavour chemistry, 7, 195 Index Infrared and Raman vibrational spect- roscopy in inorganic chemistry, 4,107 INGOLD LECTURE.Four-membered rings and reaction mechanisms, 5,149 INCOLD LECTURE.How does a reaction choose its mechanism, 10,345 Initiation of cyclization using3-methyl-cyclohex-2-enone deriva-tives, 9,265 Inorganic chemistry, bond valences, a simple structural model for, 7, 359 pyro-compounds M,[(X,O,),], 5, 269 Insect attractants of natural origin, 2,75 Insecticides, a new group of: syntheticpyrethroids, 7,473Interactions in the atmosphere of drop- lets and gases, 1,411 ion-solvent, thermodynamicsof,’ 9,381 ,metal-metal, in transition-metal complexes containing infinite chains of metal atoms, 1, 99 ,non-bonded, of atoms in organic crystals and molecules, 7, 133 Introducing a new agricultural chem- ical, 4, 77 Ion-molecule reactions in the evolution of simple organic molecules in inter- stellar clouds and planetary atmo-spheres, 6,295 Ion-pairing, contribution to ‘memory effects’, 4, 251 Ion-solvent interactions, thermo-dynamics of, 9,381 Isocyanates and ketens, a mechanistic comparison of acylation by, 4, 231 ,organic, chemistry of the prod- uction of, 3, 209 Isocyanic acid, preparation and proper- ties of, 11, 41 Isomer enumeration methods, 3, 355 Tsomerization mechanisms of square-planar complexes, 9, 185 Tsosterism and molecular modification in drug design, 8,563 Isotope effect studies of elimination re- actions, 1, 163 Isotopic hydrogen exchange in purines: mechanisms and applications, 10,329 ___ substitution effects on diffusion in liquids, 5, 215 JOHN JEYES LECTURE.Chemicals which control plant growth, 6, 261 Index LECTURE.KELVIN Across the living bar- complexes, 9, 185 ~rier, 6, 325 of the microbial hydroxylation of Ketens and isocyanates, a mechanistic steroids, 11, 371 comparison of acylation by, 4, 231 of reaction between ultimate~ Kinetics and mechanism in organic chemical carcinogens and nucleic chemistry, applications of e.s.r. spec- acid, 9, 241 MEDAL LECTURE. troscopy to, 8, 1 MELDOLA Chemical -, gas-phase, of the aspects of glycoproteins, proteo-difluoroamino-radical, 3, 17 glycans, and carbohydrate-protein __ of reactions in aqueous mixtures, complexes of human tissues, 3, 355 4, 55 MELDOLA Fe(CO),,MEDAL LECTURE. 7, 527 MEDAL LECTURE.Molecular ,8-Lactams, synthetic routes to, 5, 181 MELDOLA Lanthanide shift reagents in nuclear collisons and the semiclassical magnetic resonance spectroscopy, approximation, 5, 125 MEDALLECTURE.2, 49 MELDOLA Molecular Laser light scattering, quasielastic, shapes, 7, 507 2, 325 MELDOLA MEDAL LECTURE. N.m.r. Laser spectroscopy of ultra-trace quan- spectral change as a probe of chloro- tities, 8, 367 phyll chemistry, 6, 467 The re-Lasers, tunable, 3, 293 MELDOLAMEDAL LECTURE. Lead, environmental, in perspective, 8,63 lationship between metal carbonylLeukotrienes; a new class of biologi- clusters and supported metal cata- cally active compounds including lysts, 10, 159 SRS-A, the synthesis of, 11, 321 Meldrum’s acid, 7, 345 Ligands, cis-and trans-effects of, Metal carbonyl clusters, relationship 2, 163 with supported metal catalysts, -, compartmental: routes to homo- 10, 159 and hetero-dinuclear complexes, centres, hydrocarbon reactions 8, 199 at, 11, 283 Lignans and neolignans, the synthesis clusters in biology, 10,455 of, 11, 75 Metal-ion-promoted reactions of Liquid, surface of, 7, 329 organo-sulphur compounds, 6, 345 LECTURE.LIVERSIDGE On first looking 1-D Metallic complexes, 9, 429 into Nature’s Chemistry: Metalloboranes and metal-metal bond- I The r6le of small molecules and ing, 3, 231 ions: the transport of elements, Metal-metal bonding and metal-9, 281 loboranes, 3, 231 IT The r6le of large molecules, bonds of various orders, synergic especially proteins, 9, 325 interplay of experiment and theory in LECTURE.LIVERSIDGE Recent advances studying, 12, 35 in the study of kinetic hydrogen iso- bonds, multiple (especially qua- tope effects, 3,513 druple), 4, 27 LECTURE.LIVERSIDGE The surface of a --interactions in transit i on-me ta1 liquid, 7, 329 complexes containing infinite chains of metal atoms, 1, 99 Macrocyclic ligands, synthetic, transi- Metals, binding to proteins, 6, 139 tion-metal complexes of, 4, 421 Methyl group removal in steroid bio- Main-group elements, ring, cage, and synthesis, 10,435 cluster compounds of, 8, 315 Micelle-forming surfactant solutions, Matrix isolation technique and its ap- photophysics of molecules in, 7, 453 plication to organic chemistry, 9, 1 Micelles in aqueous solution, 6, 25 Mechanisms, chemical, and three-Microbes, use in the petrochemical in- dimensional structures of enzymes, dustry, 8, 297 1, 319 Micro-organisms, protein production -, isomerisation, of square-planar by3 8, 143 Molecular aspects of biological sur-faces, 8, 389 -beam reactive scattering, 11, 1 collisions and the semiclassical ap- proximation, 5, 125 ___ orbital theory, comparison with rotational and vibrational spec-troscopy in conformational analysis of alcohols and amines, 5, 411 ~ shapes, 7, 507 structure and organoleptic qual- ity, 7, 167 theory of small systems, 12, 251 wavefunctions, chemical inter-pretations of, 5, 79 Molybdenum and tungsten; alkoxy,amido, hydrazido, and related com- pounds of, 12, 331 Monoal kyl triazenes, 7, 377 Morphogenisis, biological, the physical chemistry of, 10, 491 Motion, molecular, and time-correlation functions, 7, 89 Multistability in open chemical reac-tion systems, 5, 359 Myoglobin and haemoglobin, electron spin resonance of, 12, 387 Natural products from echinoderms, 1, 1 ____, polycyclic polysubstituted, systematic development of strategy in, 6, 413 Neighbouring-group effects and ringconformation, development of Haworth’s concepts of, 3, 1 participation, energetics of, 2, 295 New perspectives in surface chemistry and catalysis, 6, 373 Nitrogen fixation, 1, 121 Nitroso-alkenes and nitroso-alkynes, 12, 53 C-Nitroso-compounds, electrophilic, 69.1 NMR and vibrational spectroscopicstudies, structure in solvents and solutions, 12, 1 Non-bonded interactions of atoms in organic crystals and molecules, 7, 133 Non-conventional electrophilic aro-matic substitutions and related reac- tions, 3, 167 Nuclear magnetic resonance and the periodic table, 5, 1 Index __ --__, carbon-13 in bio-synthetic studies, 4, 597 ~~methods (new) for trac- ing the future of hydrogen in bio- synthesis, 8, 539 ~~-spectral change as a probe of chlorophyll chemistry, 6, 467 _____~spectroscopy, lan-thanide shift reagents in, 2, 49 .__-______ :spin-lattice relax- ation, 4, 401 Nucleic acid, mechanisms of reaction with ultimate chemical carcinogens, 9, 241 Nucleosides and nucleotides, pyrim- idine, hubstituted, 6, 43 Nutritional chemistry of inorganictrace constituents of the diet, 10, 270 NYHOLMMEMORIALLECTURE.Chem-ical education research: Facts, findings, and consequences, 9, 365 NYHOLM LECTURE.MEMORIAL Forward from Nyholm’s March on Lecture, 3, 373 NYHOLM LECTURE.MEMORIAL Growth, change, challenge, 5, 253 NYHOLM MEMORIAL LECTURE.Ring,cage, and cluster compounds of the main group elements, 8, 315 NYHOLM LECTURE.MEMORIAL Solvingchemical problems, 11, 171 NYHOLM LECTURE.MEMORIAL Synergicinterplay of experiment and theory in studying metal-metal bonds of vari- ous orders, 12, 35 Olefin metathesis and its catalysis, 4, 155 Olefinic compounds, photochemistry of, 3, 329 On first looking into nature’s chem- istry:I The r6le of small molecules and ions: the transport of the elements, 9, 281 11 The r6le of large molecules, especially proteins, 9, 325 Organic chemistry of superoxide,6,195Organoboranes as reagents for organic synthesis, preparation of, 3, 443 Organoborates in organic synthesis: the use of alkenyl-, alkynyl-, and cyano- borates as synthetic intermediates, 6, 393 Organometallic chemistry and homoge- Index neous catalysis, the 16 and 18 elec- conductivity in, 5, 95 tron rule in, 1, 337 Polyolefins, commercial, photo-Organomethyl compounds, synthesis, degradation and stabilization of,structure, and vibrational spectra, 4, 533 9, 25 Polysaccharides, structural studies of, Organosulphur compounds, metal-ion- 10,409promoted reactions of, 6, 345 Porphyrins and relatedring systems,4,1 Organo-transition-metal complexes: Post-B,, problems in corrin syn-stability, reactivity, and orbital cor- thesis, 5, 377relations, 2, 271 Preparation of organoboranes: re-Oxygen, singlet molecular, 10, 205 agents for organic synthesis, 3, 443 and properties of isocyanicPEDLERLECTURE.Porphyrins and re-~ acid, 11,41lated ring systems, 4, 1 PRESIDENTIALADDRESS 1976.Chem- Phase boundaries, reactivity of organic istry and the new industrial revolu- molecules at, 1, 229 tion, 5, 317Phenols, anionic cyclization of, 12,213 Properties and syntheses of sweetening , .long-chain, of non-isoprenoid agents, 6,431origin, 8, 499 Prostaglandins, tomorrow’s drugs,Philosophy of chemistry, some consid- 4, 589 erations, 5, 203 -, thromboxanes, PGX: bio-Phosphates, aluminium, the chemistry synthetic products from arachidonic and binding properties of, 6, 173 acid, 6,489Phosphorus compounds, tervalent, in Prostanoids, total syntheses of, 2, 29 organic synthesis, 3, 87 Protecting ligands, q 5-cyclopentadienylPhotochemistry of azobenzene and its and q6-arene towards platinum metal derivatives, 1,481 complexes, 10, 1 -of carbonyl compounds, 1,465 Protein production by micro-__ of imines, 6, 63 organisms, 8, 143 -of olefinic compounds, 3, 329 Proteins, binding of heavy metals ~ of organic sulphur compounds, to7 6, 139 4, 523 -, r6le of in nature’s chemistry, __ of the uranyl ion, 3, 139 9, 325 -of transition-metal co-ordination Pulse radiolysis, contributions to chem- compounds-a survey, 1, 241 istry, 7, 235 Photocyclization and photochemistry Purines, isotopic hydrogen exchange in,of aryl halides, 10, 181 mechanisms and applications,Photodegradation and stabilization of 10,329commercial polyolefins, 4, 533 Pyrimidine nucleosides and nucleo-Pho tophysical and photochemical tides, 5-substituted, 6, 43 properties of flavins (isoalloxazines), Pyro-compounds, inorganic,11, 15 MA(X2 07),l, 5, 269 Photophysics of molecules in micelle- forming surfactant solutions, 7, 453 Quadruple bonds and other multiple Plant growth, control by chemicals, metal to metal bonds, 4, 27 6, 261 Quantitative drug design, 3, 273 Plantinum metal complexes, Quantum chemistry, computational,q5-cyclopentadienyl and q6-arene as growth of from 1950 to 1971, 2, 21protecting ligands towards, 10, 1 ~ mechanical tunnelling in chem- Polymer solutions, dielectric relaxation istry, 1,211in, 1, 49 Quasielastic laser light scattering, -supports, insoluble, use in organic 9 134 chemical synthesis, 3, 65 Polymerization and copolymerization Radioactive and toxic wastes: a com- of butadiene, 6, 235 parison of their control and disposal, Polymers, conductivity and super-4, 90 516 Radiolysis, pulse, contributions to chemistry, 7, 235 Raman and infrared vibrational spec- troscopy in inorganic chemistry, 4, 107 R.A. ROBINSON LECTURE.MEMORIAL Thermodynamics of hydrogen-bonded liquids, 11, 257 Reaction mechanisms, four-membered rings and, 5, 149 ______,the conversion of ammo- nium cyanate into urea, 7, 1Reactivities of carbon disulphide, car- bon dioxide, and carbonyl sulphide towards some transition-metal sys-tems, 11, 57 Reactivity of organic molecules at phase boundaries, I, 229 Recent advances in the study of kinetic hydrogen isotope effects, 3, 513 Recent syntheses in the Vitamin D field, 9,449Research in chemical education: a reassessment 1, 27 RESOURCES CONSERVATION BY NOVEL BIOLOGICAL PRO-CESSES I Grow Fats from wastes, 8, 283 I1 The Use of Microbes in the Pet- rochemical Industry, 8, 297 111 Utilization of Agricultural and Food Processing Wastes contain- ing Carbohydrates, 8, 309 Review of chemical education research and development in the U.K., 1972-1 976, 7, 317 Ring, cage, and cluster compounds of the main group elements, 8, 315 ROBERTROBINSON Post-B,,LECTURE.problems in corrin synthesis, 5, 377 ROBERT LECTURE.ROBINSON The logic of working with enzymes, 2,. 1ROBERT ROBINSON VitaminLECTURE. B 12. Retrospect and prospects, 9, 125 Rodent control, chemicals in, 1, 381 Role of chemically-induced dynamic electron polarization (CIDEP) in chemistry, 8, 29 Rotationally and vibrationally inelastic scattering of molecules, 3,407 Safety evaluation of natural and syn- thetic flavourings, 7, 185 Scale insects and aphids, chemistry of, 4, 263 Index Semistable molecules in the laboratory and in space, 11,435 Silicon compounds in organic syn-thesis, some uses of, 10, 83 containing carbonyl equiv-alents, 11,493 ~-in organic synthesis, 7, 15 16 and 18 Electron rule in or-ganometallic chemistry and homoge- neous catalysis, 1, 337 Small molecules, conformation studies on, 1, 293 Solids, surface energy of, 1, 445 Solute-solvent interactions, spec-troscopic studies of, 5, 297 Solution phenomena, the importance of solvent internal pressure and co- hesion, 4, 211 Solutions of metals: solvated elec-trons, 5,337 Solvent internal pressure and cohesion, importance to solution phenomena, 4,211Solving chemical problems, 11, 171 Some considerations on the philosophy of chemistry, 5, 203 Some recent developments in chemistryteaching in schools, 1,495Spectra of stars, absorption bands in, a crystal field approach, 5, 233 Spectral lineshapes, collisional transfer of rotational energy with, 7, 219 Spectroscopic studies of soluteesolven t interactions, 5, 297 Spectroscopy, electron, 1, 355 -, Fourier transform, chemical ap- plications of advances in, 4, 569 , laser, of ultra-trace quantities, 8, 367 ,rotational and vibrational, com- parison with molecular orbital the- ory in confirmational analysis of alcohols and amines, 5,411 , threshold electron scattering,3,467Spin-lattice relaxation: a fourth dimen- sion for proton n.m.r.spec-troscopy, 4,401 Square-planar complexes, isomer-isation mechanisms of, 9, 185 SRS-A, the synthesis of leukotrienes: a new class of biologically active com- pounds including, 11, 321 Stability, reactivity, and orbital cor-relations of organo-transition-metalcomplexes, 2, 271 Index Stereochemical choice in enzymic reac- tions, 8,447 Stereoselective synthesis of steroid side- chains, 12, 75 Steroid biosynthesis, methyl group re- moval in, 10,435 -, the mechanism of the microbial hydroxylation of, 11, 371 routes to by intramolecular Dikls-Alder reactions of o-xylylenes 9, 41 -side-chains, stereoselective syn- thesis of, 12, 75 Sterols, biosynthesis of, 1, 259 Structurs in solvents and solutions- NMR and vibrational spectroscopic studies, 12, 1 ~ of aqueous solutions of hydro-phobic solutes, experimental studies on, 2, 203 Substitution and conformation, effects of, on individual CH bond strengths in simple organic compounds,7, 399 Sugars, complex formation with cat- ions, 9,415Sulphoximides 4, 189 Sulphoximides-an update, 9, 477 Sulphur compounds, organic, photo- chemistry of, 4, 523 -, organic compounds of, metal-ion-promoted reactions of, 6, 345 -species, homonuclear, chemistry 0f, 2, 233 Superconductivity and conductivity in polymers, 5, 95 Superoxide, organic chemistry of, 6,195 Surface chemistry and catalysis, new perspectives, 6, 373 -energy of solids, 1, 445 ~ modified electrodes, 8, 259 ~ of a liquid, 7, 329 Surfaces, biological, molecular aspects 0f, 8, 389 -, solid, their acidity, 8,475 Sweetening agents, properties and syn- theses of, 6, 431 Syntheses and properties of sweetening agents, 6,431of mononuclear cyanocobalt(II1) complexes, 12, 267 , recent, in the Vitamin D field, 9,449 -, total, of prostanoids, 2, 29 Synthesis and cycloadditions, cyano- ketenes, 10, 289 and synthetic utility of halo-lactones, 8, 171 , of corrins, post-B,, problems in, 5,377 -of leukotrienes; a new class of bio-logically active compounds including SRS-A, 11, 321 -of lignans and neolignans,11, 75 of polycyclic polysubstituted nat- ural products, systematic devel-opment of strategy inl 6,413 , organic, enzymes In, 3, 387 -, organic, preparation of organo-boranes as reagents for, 3, 443 -, organic, silicon in, 7, 15 -, organic, some uses of silicon com- pounds, 10, 83 , organic, tervalent phosphoruscompounds in, 3, 87 , organic, use of inorganic polymer supports in, 3, 65 -, organic, the use of organoboratesas synthetic intermediates, 6, 393 , structure, and vibrational spectra of organomethyl compounds, 9, 25 Synthetic pyrethroids, A new group of insecticides, 7,473 routes to /I-lactams, 5, 181 Systematic development of strategy in the synthesis of polycyclic poly- substituted natural products: the ac- onite alkaloids, 6,413 TATEAND LYLE LECTURE.From carbo- hydrates to enzyme analogues, 8, 85 TATEAND LYLE LECTURE. Spin-latticerelaxation: a fourth dimension for proton n.m.r. spectroscopy, 4, 401 TATEAND LYLE LECTURE. Transition-metal oxide chelates of carbohydrate-directed macro-molecules, 8, 221 Teaching of chemistry in schools, some recent developments in, 1,495 Techniques for the kinetic study of fast reactions in solution, 11, 227 Tervalent phosphorus compounds in organic synthesis, 3, 87 Thermal, photochemical, and transition-metal mediated routes to steroids by intramolecular Diels-Alder reactions of o-xylylenes(o-quinodimethanes), 9, 41 Thermodynamics of ion -solvent inter- actions, 9, 381 Thermolysis and photolysis of di-azirines, ll, 127 Three-dimensional structures and chemical mechanisms of enzymes, 1,319 Threshold electron scattering spec-troscopy, 3, 467 Thromboxanes, prostaglandins, PGX: biosynthetic products of arachidonic acid, 6, 489 TILDEN LECTURE.Alkoxy, amido, hy- drazido, and related compounds of molybdenum and tungsten, 12, 331 TILDENLECTURE. Applications of e.s.r. spectroscopy to kinetics and mech- anism in organic chemistry, 8, 1 TILDEN Carbon-carbon bond LECTURE. formation involving boron reagents, 11, 191 TILDENLECTURE.Concerning stereo-chemical choice in enzymic reactions, 8,447 TILDENLECTURE.q 5-Cyclopentadienyland q6-arene as protecting ligands to-wards platinum metal complexes,10, 1 TILDEN LECTURE.Electrophilic C-nitroso-compounds, 6, I TILDENLECTURE.Initiation of cycliza- tion using 3-methylcyclohex-2-enone derivatives, 9, 265 TILDEN Molecular beam reac- LECTURE. tive scattering, 11, I TILDENLECTURE.New perspectives in surface chemistry and catalysis,6, 373 TILDEN Semistable molecules LECTURE. in the laboratory and in space, 11,435 TILDENLtcr'uRE. Some uses of silicon compounds in organic synthesis, 10, 83 TILDEN Valence in transition- LECTURE. metal complexes, 1,431 Time-correlation functions and molec- ular motion, 7, 89 Topological subject-chemistry, 2, 457 Trace constituents of the diet, chemical aspects, 10, 233 __ organic constituents of the diet, sources and biogenisis, 10, 280 Transimination, chemical models of enzymic, 12, 309 Transition-metal carbene complexes,chemistry and role as reaction inter- mediates, 2, 99 complexes, containing infinite chains of metal atoms, metal-metal interactions in, 1, 99 __ complexes of synthetic macro-cyclic ligands, 4, 421 complexes, valence in, 1, 43 I __ co-ordination compounds, photo- chemistry of, 1, 241 hydrido complexes, 12, 415 __ systems, reactivities of carbon disulphide, carbon dioxide, and car- bony1 sulphide systems towards, 11, 57 __ oxide chelates of carbohydrate- directed macromolecules, 8, 221 Tunable lascrs, 3, 293 Unimolecular reactions, current as-pects of, 12, 163 Uranyl ion, photochemistry of, 3, 139 Use of insoluble polymer supports in organic chemical synthesis, 3, 65 Utilization of agricultural and food processing wastes containing carbo- hydrates, 8, 309 Valence in transition-metal complexes, 1, 431 Valences, bond, a simple structural model for inorganic chemistry,7, 359 Vcry strong hydrogen bonding, 9, 91 Vibrational and NMR spectroscopicstudies, structure in solvents and solutions, 12, I , infrared, and Raman spec-troscopy in inorganic chemistry, 4, 107 ~~~ intensities in electronic transi-tions, 5, 165 ~-spectra, synthesis, and structure of ~ organomethyl compounds, 9, 25 Vibrationally and rotationally inelastic scattering of molecules, 3, 407 Viologens, electrochemistry of.10, 49 Vitamin B, 2, retrospects and prospects, 9, 12s 'Vitamin' D, chemistry of: the hor-monal calciferols, 6, 83 Vitamin D, recent syntheses in, 9, 449

ISSN:0306-0012    

DOI:10.1039/CS9831200505

出版商:RSC    

年代:1983

数据来源: RSC