Silicon in Organic Synthesis By E. W. Colvin CHEMISTRY DEPARTMENT, UNIVERSITY OF GLASGOW, GLASGOW, GI2 SQQ 1 Introduction The explosive growth of organosilicon chemistry over the past decade has created a growing awareness of its considerable synthetic utility to the organic chemist. It is the purpose of this review to demonstrate that such utility is, if anything, under-estimated ; in scope, it discusses the use of silyl-substituted reagents and substrates to activate the substrate to reaction, to direct the course of reaction, or to protect the substrate from unwanted reaction, emphasis being placed on those sequences where silicon is absent in the final product. Other sources recommended for consultation are an on-going annual survey,l a new series,2 and a short review;3 other reviews4 and monographs,5 while less timely, are of considerable value.Applications of silylation as derivatization to confer g.1.c. volatility or characterizable mass spectral fragmentation have been adequately reviewed elsewhere.6 2 Atomic Properties Silicon has the outer electronic configuration 3s23p23d0, differing from carbon in its possession of vacant d-orbitals, which can be used to expand the valency, as in SiFe2-, or to allow back-bonding. The 3p orbitals are of too high an energy to give adequate .rr-overlap with 2p orbitals, so sila-ethanes such as (1)7 are very unstable,8 and stable compounds with silicon-oxygen n-bonds are vnknown. S. S. Washburne, J. Organometallic Chem., 1974, 83, 155; 1976, 123, I.‘New Applications of Organometallic Reagents in Organic Synthesis., ed. D. Seyferth, J.Organometallic Chem. Library, Vol. 1 and 2, Elsevier, Amsterdam, 1976; see, in particular, P. F. Hudrlik, Vol. 1, p. 127; see also Vol. 4, 1977. I. Fleming, Chem. and Ind., 1975, 449. J. F. Klebe, Adv. Org. Chem., 1972,8,97; Account., Chem. Res., 1970,3,299;(b)L. Birkofer and A. Ritter in ‘Newer Methods in Preparative Organic Chemistry’, ed. W. Foerst, Academic Press, New York, 1968, Vol. 5, p. 21 I. C. Eaborn, ‘Orgsnosilicon Compounds’, Butterworths, London, 1960. A. E. Pierce, ‘Silylation of Organic Compounds’, Pierce Chemical Ca., Rockford, Illinois, 1968; G. D. Brittain and J. E. Sullivan in ‘Recent Advances in Gas Chromatography’, ed.I. I. Domsky and J. A. Perry, Marcel Dckker, New York, 1971. 0. L. Chapman, C.-C. Chang, J. Kolc, M. E. Jung, J. A. Lowe, T. J. Barton, and M. L. Tumey, J. Amer. Chem. SOC., 1976,98,7844; M. R. Chedekel, M. Skoglund, R. L. Kreeger, and H. Schechter, ibid., p. 7486. * R. E. Ballard and P. J. Wheatley, ref. 2, Vol. 2, p. 1; L. E. Gusel’nikov, N. S. Nametkin, and V. M. Vdovin, Accounts Chem. Rcs., 1975, 8, 18; N. Wiberg and G. Preiner, Angew. Chem. Internat. Edn., 1977, 16, 328; T. J. Barton and D. Banasiak, J. Amer. Chem. SOC., 1977, 99, 5199, describe the generation and trapping of a silabenzene. Silicon in Organic Synthesis Table 1 Some values of bond energieslkJ mol-1 Si-F Si-0 540-570 370-450 C-F c-0 440-465 350-360 Si-C 230-320 c-c 347 Si-H 290-320 C-H 414 Organic compounds of silicon are normally quadricovalent, the stereochemistry and mechanism of reactions at the silicon atom having been clearly expounded.9~ Silicon’s utility in organic synthesis derives from three main factors, as listed below.A. Relative Bond Strengths.-From Table 1,loit can be seen that, whereas silicon’s bonds to oxygen and fluorine are stronger than the bonds between carbon and these elements, its bonds to carbon and hydrogen are weaker. Such character- istics give rise to a wide range of thermodynamically favourable processes. B. Vacant d-Orbitals.-These orbitalsgb are of suitable energy for back-bonding with a filled 29 orbital on an adjacent atom of a first-row element, enabling silicon to stabilize, for example, an adjacent carbanion.They can also be involved in substitution reactions at silicon9 or at an adjacent atom.5 C. Relative E1ectronegativity.-Silicon has a Pauling electronegativity of I .8, and carbon a value of 2.5, making silicon-carbon bonds polarized (2), and therefore susceptible to nucleophilic attack at silicon. This leads to bond hetero- lysis, especially when the carbon fragment being expelled is a good leaving group, as exemplified in Scheme 1 ;silyl ethers behave similarly. (a)L. H. Sommer, ‘Stereochemistry, Mechanism and Silicon’, McGraw-Hill, New York, 1965; (6) H. Kwart and K. King, ‘&Orbital Involvement in the Organo-chemistry of Silicon, Phosphorus, and Sulphur’, ‘Reactivity and Structure’, ‘Concepts in Organic Chem- istry’, Springer Verlag, Berlin, 1977; see also M.E. Childs and W. P. Weber, J. Org. Chem., 1976, 41, 1799. lo L. Pauling, ‘The Nature of the Chemical Bond’, Cornell University Press, ithaca, New York, 1960, pp. 85-86; T. Cottrell, ‘The Strengths of Chemical Bonds’, Butterworths, London, 1958, pp. 270-280; see also E. A. V. Ebsworth, in ‘Organometallic Compounds of the Group iV Elements’, ed. A. G. MacDiarmid, Marcel Dekker, New York, 1968, Vol. 1, Part 1. 16 Colvin 6r 6-Si-C 0% 0-fNu : f4 H-Nu:-Si-O-R -HO-R Scheme 1 A further, profound, property is the ability of a silicon-carbon bond to stabilize an adjacent carbonium ion (3); this phenomenon can perhaps be compared with the hyperconjugative situation in (4).Si H\‘C C I IC+ C Manifestations of all the above properties will be illustrated in the succeeding reactions, which have been classified either by reaction type or by reagent type, an unavoidable but comprehensible ambiguity. 3 Directing/Stabilizing Effects of Silicon Substituents A. Carbonium Ions.-The electropositive nature of silicon results in the observ- able capacity of a carbon-silicon bond to stabilize a carbonium ion p to it,11 either by bridgingl29l3 or by hyperconjugation.l4 An elegant demonstration of bridging was reported by Eabornl2 and Jarvie;13 re-isolation of starting material from the partial solvolysis of 2-bromo-2,2-dideuterio-l-trimethyl-silylethane (5) yielded material in which the deuterium had been extensively scrambled between C-1 and C-2, consistent with a mechanism involving an l1 A. W.P. Jarvie, Organometallic Chem. Rev. (A), 1970, 6, 153. M. A. Cooke, C. Eaborn, and D. R. M. Walton, J. Organometallic Chem., 1970, 24, 301. l3 A. J. Bourne and A. W. P. Jarvie, J. Organometallic Chem., 1970, 24, 335. l4 T. G.Traylor, W. Hanstein, H. J. Berwin, N. A. Clinton, and R. S. Braun, J. Amer. Chem. SOC.,1971, 93, 5715. Silicon in Organic Synthesis anchimerically assisted ionization of the C-Br bond to give a silacyclopropen- ium ion (6) (Scheme 2). There also exists evidence that cations ct to silicon are destabilized.'j Ab initio SCF MO calculations on silyl-substituted alkanes, alkyl radicals, and carbonium ions show that the carbonium ion is destabilized by an ct-silyl group and stabilized by a 13-silyl group by comparison with the carbon analogues.These results are consistent with observations on the rates of SN~solvolysis of silylmethyl halides (Scheme 2). R,SiCH,CH,X s\ 1 +faster than analogous C compound R,SiC H ,X s\ 1---+- slower than analogous C compound Scheme 2 (i) Silyl-arenes. Such stabilization has been studied extensively in the aromatic Theserie~.l~,~~Hammett electrophilic para-substitution constant for the Me3SiCH2 group is -0.66.16 This closely approximates to the value for the Me0 grol.jp, viz. -0.74, implying that in general terms a Me3Si group p to a carbonium ion stabilizes that ion to about the same extent as does a Me0 group u to it.This has been put to practical use: under normal conditions of electrophilic aromatic substitution, such substitution on silyl-arenes will take place at the site of the silyl gro~p,~~,~~ even when the other ring substituents do not favour such regiospecificity20*21 (Scheme 3); one is of course, faced with the not inconsiderable initial problem of preparing the silyl-arenes. (ii) Vinyl-silanes. Similarly, the orientation of electrophilic attack on alkenes can be controlled by the introduction of a silyl substituent, as can (in appropriate cases) the stereochemistry. An example can be seen in the ability of vinyl- l5 C. Eaborn, F. Feichtmayr, M. Horn, and J. R. Murrell, J. Organometalfic Chem., 1974, 77, 39.l6 W. Hanstein, H. J. Berwin, and T. G. Traylor, J. Amer. Chem. SOC.,1970, 92, 829, 7476. l7 C. Eaborn and K. C. Pande, J. Chem. SOC.,1960, 1566. C. Eaborn, A. A. Najam, and D. R. M. Walton, J.C.S. Perkin I, 1972, 2481. la J. B. F. Lloyd and P. A. Ongley, Tetrahedron, 1964, 20, 2185. *O V. Chvalovski and V. Baiant, Coll. Czech. Chem. Comm., 1951, 16,580. a1 T. Hashimodo, J. Pharm. SOC.Japan, 1967, 87, 528; G. Felix, J. Dunogues, F. Pisciotti, and R. Calas, Angew. Chem. Internat. Edn., 1977, 16, 488. Colvin CO,H CO,H Scheme 3 silanes to transfer the vinyl group to acid chlorides (Scheme 4)in an attractive synthesis22 of $-unsaturated ketones. 0 Scheme 4 The stereospecific synthesis of both isomers of vinyl-silanes has stimulated much activity, most existing method~logies~~ starting with alkynes; a recent route from ketones involves electrophilic trapping of vinyl anions (Scheme 5).24 r 1 L J Reagents: i, BunLi; ii, Me,SiCl Scheme 5 23 J.-P.Pillot, J. Dunogues, and R. Calas, Compt. rend., 1974, 278, C, 787, 789; Bull. SOC. cliirn. France, 1975, 2143; I. Fleming and A. Pearce, I.C.S. Chem. Comm., 1975, 633; for a related use of cyclopropylsilanes, see M. Grignon-Dubois, J. Dunogues, and R. Calas, Synthesis, 1976, 737. 23 C. Eaborn and R. W. Bott in ‘Organometallic Compounds of the Group IV Elements’, ed. A. G. MacDiarmid, Marcel Dekker, New York, 1968, Vol. 1, Part 1; J. J. Eisch and G. A. Damasevitz, J. Org. Chem., 1976, 41, 2214; K. Uchida, K. Utimoto, and H.Nozaki, ibid., pp. 2215, 2941; R. Koster and L. A. Hagelee, Synthesis, 1976, 118. For different approaches, see K. Sachdev, Tetrahedron Letters, 1976, 4041 ;H. Westmijze, J. Meijer, and P. Vermeer, ibid., 1977, 1823; M. Obayashi, K. Utimoto, and H. Nozaki, ibid., p. 1805. 2p T. H. Chan, A. Baldassarre, and D. Massuda, Synthesis, 1976, 801; R. T. Taylor, C. R. Degenhardt, W. P. Melega, and L. A. Paquette, Tetrahedron Letters, 1977, 159; see also R. H. Shapiro, Org. Reactions, 1976, 23, 405. Silicon in Organic Synthesis The powerful directing effect of silicon in such systems can be seen in the stereospecific reactions shown in Scheme 6. The mechanism proposed25 is that, simultaneously with attack of the electrophile on the double bond, rotation occurs about the developing C-C single bond in such a direction as to permit the C-Si bond to stabilize the benzylic carbonium-ion centre continuously; rotation in the opposite direction would bring the C-Si bond into the nodal plane of the developing ion, and so preclude such continuity.1'H H E Ph SiMe, H H + PhXE L J H E+ and Ph &IMe3 H H --PhPhHXE Scheme 6 This concept has been shown to be generally applicable,26 mono-and di-substituted vinyl-silanes undergoing electrophile-induced desilylation with strict retention of configuration, and its utility has been extended by Chan,27 by developing simple stereospecific routes to disubstituted vinyl-silanes (Scheme 7). Interestingly, the treatment of vinyl-silanes with molar equivalents of chlorine or bromine results in apparent tram-addition.The resulting dihalides, on anti-periplanar elimination of the elements of trimethylsilyl halide, yield vinyl halides of opposite sterochemistry28 (Scheme 8); iodination results in either 25 K. E. Koenig and W. P. Weber, Tetrahedron Letters, 1973, 2533. 26 K. Utimoto, M. Kitai, and H. Nozaki, Tetrahedron Letters, 1975, 2825. 37 T. H. Chan, W. Mychajlowskij, R. S. Ong, and D. N. Harpp, J. Organometallic Chern., 1976, 107, C1; W. Mychajlowskij and T.H. Chan, Tetrahedron Letters, 1976, 4439; for n.m.r. and g.c. differentiation of geometric isomers of vinylsilanes see T. H. Chan, W. Mychajlowskij, and R. Amoroux, Tetrahedron Letters, 1977, 1605.28 R. B. Miller and T. Reichenbach, Tetrahedron Letters, 1974, 543. 20 Colvin H CH,CI H CH,R2 Me,Si Lih1 SiMe:, OH SiMe, ~ R X W H H SiMe, OAc Reagents: i, R’CHO; ii, SOCl,; iii, LiCuRa, or R2,CuMgBr Scheme 7 retention or inversion, as shown. Finally, HBr in pentane, which adds sluggishly to terminal alkynes, giving meagre yields of 2-bromoalk-1 -enes, reacts smoothly29 with trimethylsilyl-alkynes to give the desired bromides in high yield (Scheme 8). I. II iii-vRC-CH RC-CSiMe, -Rw”i””H H SiMe, RHR 1RHL xxxR\ HXHHHI Reagents: i, EtMgBr; ii, Me,SiCl; iii, (C,H,,),BH; iv, Ac,O-heat; v, NaOH-H,O,; vi, C1, or Br,; vii, NaOMe; viii, I,; ix, I,-CF,CO,Ag; x, KF-DMSO-H20; xi, HBr Scheme 8 (iii) Allyl-silanes.Allyl-silanes, as homologues of vinyl-silanes, undergo similarly controlled regiospecific electrophilic attack, the electrophile bonding to the y-carbon atom, which results in a net shift of position of the double bond3O (Scheme 9). R. K. Boeckman and D. M. Blum, J. Org. Chem., 1974, 39, 3307. 30 R. Calas and E. Frainnet, Compt. rend., 1955, 240, 203; 1956, 243, 595. 21 Silicon in Organic Synthesis Vinyl-silanes E+4ASiMe, +ASiMe, Allyl-silanes r 1 Scheme 9 The allyl-silane (7) has been converted into the aglucone ethanoate (8)3l of loganin, and, by a separate series of transformations, into the prostaglandin intermediate (9)32 (Scheme 10).A related study33 of the synthetic utility of l-trimethylsilylbuta-1,3-diene(10) as a Diels-Alder dienophile has been reported.An example of the powerful directing effect of silicon in such systems can be seen in a preparation of synthetically versatile allyl sulphides by acid-catalysed rearrangement of the more accessible /Lhydroxyalkyl phenyl sulphides, when, with silicon's assistance, migration from a secondary to a tertiary cationic site is observeds4 (Scheme 1 1). Similarly, the allyl-silane (1 1) gives solely35 the alkene (13),in contrast to (12), which gives a gross mixture of alkene isomers (Scheme 11); predictably, the rearrangement is faster with the silylated substrate. As with vinyl-silanes, allyl-silanes can be induced to transfer the allyl group to suitable electrophiles,36937 leading, in one case,38 to a ready synthesis of artemesia ketone (14)(Scheme 12).Allyl-silanes react regiospecifically with chlorosulphonyl isocyanate to give intermediate p-lactams, which rearrange thermally to lactim ethers (1 5) ; such species can be hydrolysed to acids,31 or, by treatment with ~yridine,~~ converted into nitriles (Scheme 13). To summarize, the two modes of interaction of a carbon-silicon bond with a 31 B.-W. Au-Yeung and I. Fleming, J.C.S. Chern. Cornm., 1977, 81. 31 B.-W. Au-Yeung and I. Fleming, J.C.S. Chern. Cornrn., 1977, 79. 33 M. J. Carter and I. Fleming, J.C.S. Chern. Cornrn., 1976, 679; I. Fleming and A. Percival, ibid., p. 681. 34 P. Brownbridge, 1. Fleming, A. Pearce, and S. Warren,J.C.S. Chern. Conrrn., 1976, 751 and references therein; P.Brownbridge and S. Warren, J.C.S. Perkin I, 1977, I 13 I. 36 I. Fleming, A. Pearce, and R. L. Snowden, J.C.S. Chern. Cornrn., 1976, 182. 36 A. Hosomi and H. Sakurai, Tetrahedron Letters, 1976, 1295; for conjugate addition to enones, see J. Arner. Chern. SOC.,1977, 99, 1673. 37 I. Ojima, Y. Miyazawa, and M. Kumagai,J.C.S. Chern. Cornni., 1976, 927; for more highly functionalized allylsilanes, see I. Ojima, M. Kumagai, and Y. Miyazawa, Tetralietlrotz Letters, 1977, 1385; K. Itoh, M. Fukui, and Y. Kurachi, J.C.S. Chenz. Cumin., 1977, 500. 38 J.-P. Pillot, J. Dunogues, and R. Calas, Tetrahedron Letters, 1976, 1871 ;see also G. Deleris, J. Dunogues, and R. Calas, ibid., p. 2449. 3@ G. Deleris, J. Dunogues, and R. Calas, J.Organornetallic Chern., 1976, 116, C45. Colvin Me H&-OH*# /MeOK SiMe, (7) MeO 0 0 -0Eg + Q -% '03+ (J:>o I0 0SiMe, 0 SiMe, (10) Scheme 10 5 products OMe (1 1) R = SiMe, (12) R = H OMe Scheme 11 (13) Silicon in Organic Synthesis R p.,ocl (14) Reagents: i, TiCl,; ii, Mg-Et,O; iii, Me3SiC1; iv, and AlCI3 Scheme 12 SiMe, 0 S0,CI (15) Reagents: i, CISOzNCO; ii, pyridine Scheme 13 cationic centre can be represented as shown in Scheme 9. In subsequent sections, more examples of such behaviour will be illustrated. B. Carbaniom-(p-d)n-Back-bonding between silicon and carbon, and con- sequent electron withdrawal from carbon, is sufficiently strong in many cases to stabilize an a-silyl carbanion.Using strong base, a proton can be removed from even tetramethyl~i.lane.4~ In most cases, however, the carbanion is also flanked by another electron-withdrawing group; in addition, the reaction partner is normally a carbonyl compound, and the final product is an alkene: these reactions are discussed in Section 4. Two reactions do not fall into this general class. The regiospecific addition of vinyl ketones to enolate anions (kinetically generated under aprotic con- ditions) is not normally practicable, owing to extensive polymerization of vinyl ketones under such conditions and relatively rapid proton transfer, resulting in 40 D. J. Peterson, J. Organonietallic Chem., 1967, 9, 373. Colvin loss of enolate regiospecificity.The silylated methyl vinyl ketone (16) successfully traps41 even readily equilibrated enolate anions (Scheme 14), with the inter- mediacy of the relatively stable, and hence non-basic, anion (17); the silyl group in the product, being now a-ketonic, is readily displaced by nucleophiles. SiEt, 0 SiEt, Reagents: i, Li-NH,-ButOH (1 equiv.); ii, Me,SiCl, then isolation; iii. LiMe; iv, NH,CI- H,O; v, NaOMe-MeOH. Scheme 14 Phenylselenomethyltrimethylsilane (1 8) furnishes a carbanion which reacts42 smoothly with primary alkyl bromides and iodides. The alkylated products, after treatment with hydrogen peroxide, did not produce vinyl-silanes by selen- oxide elimination, but did afford the homologous aldehydes directly (Scheme 15) (see Section 5).Extension to provide a general acyl carbanion equivalent should be possible. Reagents: i, LiNPr,'-THF, at -78°C; ii, RCH,X; iii, 30% H,O, Scheme 15 41 (a) G. Stork and B. Ganem, J. Amer. Chem. Soc., 1973, 95, 6152; (b) R. K. Boeckman, ibid., p. 6867; J. Org. Chem., 1973, 38, 4450; J. Arner. Chem. SOC.,1974, 96, 6179; (c) G. Stork and J. Singh, ibid., p. 6181; for a related process with a-silyl propenoate esters, see S. L. Hartzell and M. W. Rathke, Tetrahedron Letters, 1976, 2737. 4a K. Sachdev and H. S. Sachdev, Tetrahedron Letters, 1976, 4223; see also H. J. Reich and S. K. Shah, J. Org. Chem., 1977, 42, 1773. Silicon in Organic Synthesis 4 P-Hydroxy-silanes as Alkene Precursors In most examples of processes involving or-silyl carbanionoids, the reaction partner is a carbonyl compound, and the p-hydroxy-silane thus formed can be converted into an alkene by thermodynamically favourable p-elimination of trimethylsilanol or its equivalent. The classic example of this process, which is analogous to the Wittig reaction and often superior to it, especially for the introduction of exomethylene units,43 is known as Peterson olefination44 (Scheme 16).+ Me,SiO M Scheme 16 The factors influencing the ease and stereochemical requirements of this elimination have been delineated by several groups. It has been observed that lithium and magfiesium salts of P-hydroxy-silanes undergo elimination more readily44 when the resulting alkene is non-terminal than when it is terminal.Treatment of P-hydroxy-silanes with ethanoyl chloride or thionyl chloride45 is effective in promoting elimination. In a of the stereochemistry of silanol elimination, the silane (19) (of unknown relative configuration, but diastereoisomerically almost pure) gave almost exclusively E-alkene, the expected product of syn-elimination from the threo-form, when treated with potassium hydride (Scheme 17). Boron trifluoride etherate, on the other hand, gave 2-alkene, the expected product of anti-elim-ination. These different elimination pathways reflect the requirement, in the former case, for syn-elimination to occur in order that an Si-0 bond might Pr L >I e,,Si OH / -\ H->-<-pr Pr ------A Pr Pr Pr H \=c/ (19) Reagents: i, KH; ii, BF,, Et,O Scheme 17 43 R.K. Boeckman and S. M. Silver, Tetrahedron Letters, 1973, 3497. 44 D. J. Peterson, J. Org. Chem., 1968,33,780; see also F. A. Carey and J. R. Toler, ibid., 1976, 41, 1966. 45 T. H. Chan and E. Chang J. Org. Chem., 1974, 39, 3264. 46 P. F. Hudrlik and D. Peterson, J. Amer. Chem. SOC.,1975, 97, 1464. 26 Colvin be formed; in the latter case, an Si-F bond is formed, and the usual stereoeiectronic factors determine the geometry of elimination. This same general process can be used for the stereoselective production of trisubstituted alkenes,47 or, by reaction with an aldehyde, 1,2-disubstituted alkenes. The requisite reagents are generated as Grignard by direct lithiation of a suitably substituted silane or addition of an alkyl-lithium to a vinyl-~ilane,~~or by cleavage of an a-silylmethyl selenide ;49 if the epoxy-silane (20) is readily available (see Section 5), it undergoes a regiospecific ring opening on treatment50 with lithium dialkylcuprates, once again producing alkenes (Scheme 18).R',SiCH,Cl -!-+ R',SiCH,MgCl R1,SiCH,Ar -!& R1,SiCHAr I Li R',Si iii ~ Li II R',SiCHSeR4 R',SiCHR3 I I R3 Li 0-M-Reagents: i, Mg; ii, BunLi; iii, R2Li; iv, R6COR7; v, LiCuRS, Scheme 18 47 K. Utimoto, M. Obayashi, and H. Nozaki, J. Org. Chem., 1976, 41, 2940. T. H. Chan, E. Chang, and E. Vinokur, Tetrahedron Letters, 1970, 1137; T. H. Chan and E. Chang, J. Org. Chein., 1974, 39, 3264; for the original observation, see L.F. Cason and H. G. Brooks, rhicl., 1954, 19, 1278; see also P. R. Jones and T. F. 0. Lim, J. Amer. Chem. SOC.,1977, 99, 2013. J9 W. Dumont and A. Krief, Angew. Chein. Internat. Edn., 1976, 15, 161. 5u P. F. Hudrlik, D. Peterson, and R. J. Rona, J. Org. Chem., 1975, 40, 2263. 27 Silicon in Organic Synthesis The analogous direct conversion of aldehydes or ketones into homologated @-unsaturated esters (Scheme 19) has been de~cribed.~la~~ Reagent: i, R2COR3 Scheme 19 Trimethylsilylpotassium smoothly converts oxirans into alkenes, nucleo-philic ring opening being followed by spontaneous /?-elimination; this provides an excellent alternative53 to the earlier Wittig-based methodsS4 of geometric isomerization of alkenes (Scheme 20).r 0-1 Reagents: i, Me,SiSiMe,-KOMe-HMPA Scheme 20 The silicon- and phosphorus-substituted diazomethanes (21) and (22), as their metal salts, convert55 some ketones and aldehydes into homologous alkynes (Scheme 21); evidence has been presented in the phosphorus case, and (by implication) in the silicon analogue also; this implies that there is initial elimination to give a diazovinyl species, which then undergoes skeletal rearrange- ment. 51 K. Shimoji, H. Taguchi, K. Oshima, H. Yamamoto, and H. Nozaki, J. Amer. Chem. SOC., 1974, 96, 1620; H. Taguchi, K. Shimoji, H. Yamamoto, and H. Nozaki, Bull. Chem. SOC. Japan, 1974, 47, 2529. 52 S. L. Hartzell, D. F. Sullivan, and M. W. Rathke, Tetrahedron Letters, 1974, 1403; for a/?-unsaturated thiol esters, see D. H.Lucast and J. Wemple, ibid., 1977, 1103; for $3-un-saturated acids see P. A. Grieco, C.-L. J. Wang, and J. S. Burke, J.C.S. Chem. Comm., 1975, 537. 53 P. B. Dervan and M. A. Shippey, J. Amer. Chem. SOC.,1976, 98, 1265; for the analogous use of PhMe,SiLi, see M. T. Reetz and M. Plachky, Sj'nthesis, 1976, 199; for other func- tional silyl anions, see W. C. Still, J. Org. Chem., 1976,41, 3063; H. Watanabe, K. Higuchi, M. Kobayashi, M. Hara, Y. Koike, T. Kitahara, and Y. Nagai, J.C.S. Chem. Comm., 1977, 534. 54 E. Vedejs and P. L. Fuchs, J. Amer. Chem. SOC.,1973, 95, 822; A. J. Bridges and G. H. Whitham, J.C.S. Chem. Comm., 1974, 142; see also P. E. Sonnet and J. E. Oliver, J. Org. Chem., 1976, 41, 3279.56 E. W. Colvin and B. J. Hamill, J.C.S. Perkin I, 1977, 869; see also ref. 64c 28 Colvin Me,SiCN '1 I M R1CECR2i-.-.i-//+ N2 Scheme 21 A final example of the mechanistic parallel between silicon and phosphorus involves the silylated dithian anion (23), which, like the phosphorus analogue (24), converts56 carbonyl compounds into synthetically useful keten thioacetals (Scheme 22); whereas the use of the ylide (24) is restricted to aldehydes, the lithio-salt (23) can be applied generally. Vinyl sulphoxides are obtainable57 using the metallated species (25); the value of this method is reduced somewhat by the difficulty experienced in preparing (25). The reaction of 1-triphenylsilylvinyl-lithium with aldehydes leads to allenes5* (Scheme 23); in such cases, silanoxide elimination does not occur readily, and fluoride ion is used to displace the silyl moiety.It seems, however, that this reaction cannot be extended to ketones to produce 1,1-disubstituted allenes; in such cases, elimination does not occur, although the silyl group is lost.59 Symmetrical allenes6O are formed by the reaction of the phosphorane (26) with aryl ketones; alkenes are formed simultaneously, by displacement of a silyl group from the phosphorane followed by a normal Wittig reaction (Scheme 24); variation of the ylide and/or the ketone leads to a range of products. 56 F. A. Carey and A. S. Court, J. Org. Chem., 1972,37, 1926; P. F. Jones and M. F. Lappert, J.C.S. Chem. Comm., 1972, 526; D.Seebach, B.-Th. Grobel, A. K. Beck, M. Braun, and K.-H. Geiss, Angew. Chem. Internat. Edn., 1972, 11, 443; D. Seebach, M. Kolb, and B.-Th. Grobel, Tetrahedron Letters, 1974, 3171 ; B.-Th. Grobel, R. Burstinghaus, and D. Seebach, Synthesis, 1976, 121. 57 F. A. Carey and 0. Hernandez, J. Org. Chem., 1973, 38, 2670; see also F. A. Carey and A. S. Court, ibid., 1972, 37, 939, and ref. 44. 58 T. H. Chan and W. Mychajlowskij, Tetrahedron Letters, 1974, 171. 59 T. H. Chan and W. Mychajlowskij, Tetrahedron Letters, 1974, 3479. 8o H. Schmidbaur and H. Stuhler, Angew. Chem. Internat. Edn., 1973,12, 321 ; H. Schmidbaur, Accounts Chem. Res., 1975, 8, 62. 29 Silicon in Organic Synthesis 0 ?n nsysMe3Si Li LiPhsYSiMe3 (MeO),P+ (25) R' R' R' )--CHO )-co,H R+HO R? R? R3 Reagents: i, R1COR2;ii, Et,SiH-CF3C0,H; iii, HgII; iv, R3Li Scheme 22 Ph,Si Li>-+ SiMe, Me,Si Lib=+ Reagents: i, KF-DMSO Scheme 23 The treatment of a variety of ketones with trimethylsilyl chloride and zinc produces alkenes (Scheme 25);this deoxygenation may be related to the Peterson reaction, but the available evidence61 favours a carbenoid pathway.5 Vinyl-silanes and ap-Epoxy-silanes Vinyl-silanes are readily converted into ap-epoxy-silanes, which, by acid-catalysed nucleophilic displacement of the silyl group, efficiently give carbonyl 61 W. B. Motherwell, J.C.S. Chem. Comm., 1973, 935. Colvin Ph,: -c H Si M e3 \ OHI-Ph,C-C-Si Me,I +PPh, Ph,C =CH, Ph Ph Ph \ / I \C=C-;Ph, -Ph/ Reagent: i, PhCOPh Scheme 24 Reagents: i, Zn-Me,SiCI Scheme 25 compounds.62 This synthetic equivalence has found use in several general routes to carbonyl compounds, utilizing cc-lithio-vinyl-silanes,63 cc-lithio-disilylmethanes,wa or-chloro-cc-trimethylsilyl ~arbanions,6*~and cc-lithio-ap-epoxy-silanes65 (Scheme 26).Route@ to p-lithio-vinyl silanes have been devel- oped, adding further scope to this process. It has also been applied in a regio- specific alternative to the Robinson annelation sequence, using ally1 halides67 such as (27); interestingly, displacement of the silyl group in such cases is easier than in simple ccp-epoxy-silanes, possibly owing to participation by the neighbouring carbonyl group (Scheme 27).Similarly, the silyl vinylcuprate (28) effects conjugate addition68 of an ethanoyl anion equivalent. 62 G. Stork and E. Colvin, J. Amer. Chem. Soc., 1971, 93, 2080. 63 B.-Th. Grobel and D. Seebach, Angew. Chem. Internat. Edn., 1974, 13, 83; Chem. Ber., 1977, 110, 852, 867; see also K. Sachdev, Tetrahedron Letters, 1976, 4041. 64 (a)H. Sakurai, K. Nishiwaka, and M. Kira, Tetrahedron Letters, 1973,4193; (b)C. Burford, F. Cooke, E. Ehlinger, and P. Magnus, J. Amer. Chem. SOC.,1977,99,4536; F. Cooke and P. Magnus, J.C.S. Chem. Comm., 1977, 513; (c) see also U. Schollkopf and H.-U. Scholz, Synthesis, 1976, 271. 65 J. J. Eisch and J. E. Galle, J. Amer. Chem. SOC.,1976, 98, 4646. 66 R. F. Cunico and F. J. Clayton, J. Org. Chem., 1976, 41, 1480. 67 G.Stork and M. E. Jung, J. Amer. Chem. SOC.,1974, 96, 3682; G. Stork, M. E. Jung, E. Colvin, and Y. Noel, ibid., p. 3684. 68 R. K. Boeckman and K. J. Bruza, Tetrahedron Letters, 1974, 3365. 7 31 Silicon in Organic Synthesis H0NiMe3 Me3Si SiMe, (Me,Si),CLi R3 Ph,Si PLi I* I ii-iv R' Me3SiCHCI Li Me3Si vi vii ix1 1 1 Li R3 Me3Si Me,SiCCII Ph3Siyo\I MePHR2 Rl ii Me,Si R Vlll R' Reagents: i, H+ Nu-; ii, CH,O; iii, Br,; iv, ButLi; v, RX; vi, RTHO; vii, BusLi; viii, R4COR5;ix, Me1 Scheme 26 Me3sy ---;a-Me& fJJ-0 + I (27) Scheme 27 (Me3Si CuLi Colvin ap-Epoxy-silanes undergo electrophile-catalysed ring opening to give products of predominant cc-~leavage.699~0 This result is, at first sight, rather unexpected, as, although a fully developed carbonium ion may not be involved in such an opening, one would still expect P-cleavage to predominate, in view of the well- documented stability of cations ,8 to silicon (see Section 3).However, the relative orientations of the C-Si and the P C-0 bonds deviate markedly from the coplanar alignment favourable for stabilization of a developing positive charge by the C-Si bond. Indeed, the preference for cc-opening in these reactions suggests that the silyl group may actually facilitate71 bimolecular nucleophilic displace- ments a to silicon. In contrast, /!$+epoxy-silanes have no such geometric con- straint, and are not only more labile, but open by exclusive P-clea~age,~~ via a developing p carbonium ion.It would therefore appear that the conversion of ccP-epoxy-silanes into carbonyl compounds proceeds by initial solvolysis to ap-dihydroxy-silanes, followed by acid-catalysed elimination; isolation73 of the glycol (29) lends credence to this postulate, as here the trimethylsilyl groups and hydroxy-groups cannot fulfil the preferred arrti-periplanar geometry for acid-catalysed elimination (Scheme 28). Such stability to acid suggestsi4 that the standard hydrolysis conditions can be used only for those cases leading to acyclic carbonyl compounds; in principle, base-induced elimination, with its different stereochemical requirement, could be used for cyclic cases. ccp-Epoxy-silanes undergo thermolysis75.76 to the iso- meric silyl enol ethers; this route is unlikely to compete with the more standard methods for such compounds (see Section 7).Simple ap-epoxy-silanes undergo77 desilylation on treatment with fluoride ion (Scheme 29) with retent ion of stereochemistry. Chloromethyl ap-epoxy- silanes such as (30), on the other hand, give allene oxides as products of elimina-tion;i8 this provides a reliable and easy entry into the allene oxide-oxyallyl zwitterion-cyclopropanone set of valence-bond tautomers, and has recently resulted in the isolation79 of t-butylallene oxide (Scheme 29). 68 P. F. Hudrlik, R. N. Misra, G. P. Withers, A. M. Hudrlik, R. J. Rona, and J. P. Arcoleo, Tetrahedron Letters, 1976, 1453; see also ref. 50; for an application see M.Obayashi, K. Utimoto, and H. Nozaki, ibid., 1977, 1807. 70 5. J. Eisch and J. T. Trainor, J. Org. Chem., 1963, 28, 2870; J. J. Eisch and J. E. Galle, ibid., 1976, 41, 2615. 71 C. Eaborn and J. C. Jeffrey, J. Chem. Soc., 1954, 4266. 72 P. F. Hudrlik and G. P. Withers, Tetrahedron Letters, 1976, 29. 73 C. M. Robbins and G. H. Whitham, J.C.S. Chem. Comm., 1976,697. 74 P. F. Hudrlik, J. P. Arcoleo, R. H. Schwartz, R. N. Misra, and R. J. Rona, Tetrahedron Letters, 1977, 591 ; for an application to produce heteroatom-substituted alkenes, see P. F. Hudrlik, A. M. Hudrlik, R. J. Rona, R. N. Misra, and G. P. Withers, J. Amer. Chem. Soc., 1977, 99, 1993. 76 P. F. Hudrlik, C.-N. Wan, and G. P. Withers, Tetrahedron Letters, 1976, 1449.76 A. R. Bassingdale, A. G. Brook, P. Chen, and J. Lennon, J. Organometallic Chem., 1975, 94, c21. 77 T. H. Chan, P. W. K. Lau, and M. P. Li, Tetrahedron Letters, 1976, 2667. 78 T. H. Chan, M. P. Li, W. Mychajlowskij, and D. N. Harpp, Tetrahedron Letters, 1974, 351 1. 79 T. H. Chan, B. S. Ong, and W. Mychajlowskij, Tetrahedron Letters, 1976, 3253; B. S. Ong and T. H. Chan, ibid., p. 3257. Silicon in Organic Synthesis H /O$iM', I + f J x-SiMe, H,O+ Si Me, OH (29)Scheme 28 (30)Reagent: i, F-Scheme 29 Dihalogenocarbene addition to vinyl-silanes, followed by fluoride-ion-induced desilylation, similarly gives entry into strained halogenocyclopropenes80 and the transient preparation of a bicyclo[2,2,2]oct-l -ene.81 6 Protection of Functional Groups This section will concentrate on the protection afforded to various functional groups by their conversion into silyl derivatives, considerable emphasis being T.H. Chan and D. Massuda, Tetrahedron Letters, 1975, 3383. T. H. Chan and D. Massuda, J. Amer. Chem. SOC.,1977, 99,936. Colvin placed on cases where the silyl group modifies, in a positive sense, the reactivity of the parent functional group. Specifically excluded are references to silylation as a derivatization procedure for chromatography or mass spectrometry, both fields being adequately covered else~here.~96 A. Protection of Alcohols.-The protection of hydroxy-groups as their trimethyl- silyl ethers has found use in several syntheses of natural produ~ts,*~-~~ but the solvolytic lability of such ethers limits their utility.t-Butyldimethylsilyl ethers, on the other hand, are ca. lo* times less readily hydrolysed,85 and can survive several sequential synthetic operation^.^^-*^ This group is stable to aqueous or alcoholic base under the conditions of ethanoate hydrolysis, and also to pal- ladium-catalysed hydrogenolysis, and it resists mild reducing and oxidizing agents.90 It is unaffected by hydrazine hydrate under conditions used to remove P-benzoylpropanoyl or N-acyl groups, but can be removed efficiently with fluoride ion or SO% ethanoic acid; iron(rr1) chloride in ethanoic anhydride trans- forms such ethers directly into the corresponding ethan~ates,~~ with chiral retention.A final important advantage is that the formation of t-butyldimethyl- silyl ethers does not introduce further chirality, in contrast to the use of tetra- hydropyrany 1 ethers. (i) Formation. The conversion of alcohols into their silyl ethers is normally achieved under very mild conditions, using the appropriate silyl chloride in the presence of a tertiary amine base, including the efficient combinationg2 of bistrimethylsilylamine, trimethylsilyl chloride, and pyridine; silyl-transfer reagents such as (31)93 and (32)94are of value. Imidazole is a most effective OSi Me, MeANSiMe, Me,SiN HS03SiMe, 82 E. J. Corey and B. B. Snider, J. Amer. Chem. SOC.,1972, 94, 2549. 83 R. Wies and P. Pfaender, Annalen, 1973, 1269. 84 E. Negishi, G.Lew, and T. Yoshida, J.C.S. Chem. Cornm., 1973, 874. 85 Ref. 9, pp. 132, 138. 86 E. J. Corey and A. Venkateswarlu, J. Amer. Chem. Soc., 1972,94,6190;see also D. A. Evans, T. C. Crawford, R. C. Thomas, and J. A. Walker, J. Org. Chem., 1976, 41, 3947. *7 G. D. Prestwich and J. N. Labowitz, J. Amm. Chem. Sor., 1974, 96, 7103. 88 E. J. Corey and H. S. Sachdev, J. Amer. Chem. SOC.,1973, 95, 8483. K. K. Ogilvie and D. J. Iwacha, Tetrahedron Letfers, 1973, 317. 9oE.W. Yankee, U. Axen, and G. L. Bundy, J. Amer. Chem. SOC.,1974, 96, 5865; see also ref, 86. 91 8. Ganem and V. R. Small, J. Org. Chem., 1974, 39, 3728. 92 C. C. Sweeley, R. Bentley, M. Makita, and W. W. Wells, J. Amer. Chem. SOC.,1963, 85, 2497; H. E. Carter and R. C. Gaver, J.LipidRes., 1967, 8, 391. 93 J. F. Klebe, H. Finkbeiner, and D. M. White, J. Amer. Chem. Soc., 1966, 88, 3390; M. N. Galbraith, D. H. S. Horn, E. Middleton, and R. J. Hackney, Chem. Comm., 1968, 466; see also L. Birkofer, A. Ritter, and F. Bentz, Chem. Ber., 1964, 97,2196. 91 B. E. Cooper and S. Westall, J. Organometallic Chem., 1976, 118, 135. Silicon in Organic Synthesis catalyst, finding particular utility86 in the preparation of t-butyldimethylsilyl ethers. Considerable regio- and stereo-selectivity is readily attained. The rates of silylation of secondary alcohols by bistrimethylsilylamine in pyridine at 25 "C vary95 over a factor of 103 from endu-fenchol to exo-norborneol. t-Butyldimethyl- silyl chloride reactsg6 selectively with the 3P-hydroxy-group of androst-5-ene- 3/3,17P-diol.Trimethylsilyldiethylamine silylates equatorial hydroxy-groups,g7 axial alcohols being unreactive under the conditions used ;it selectively silylates the prostaglandin F series at the 1 1-, and, if secondary, the 15-position, allowing clean conversiong8 into the E series (Scheme 30). The demands made by the prostaglandins, in synthesis and interconversion, have done much to stimulate activity in studies of methods of protection that involve silyl ethers. OH '-CO,MePGFZamethyl ester -Me,SiO t)SiMe, .. ... 11, Illi PGE, methyl ester Reagents: i, Et,NSiMe,; ii, Cr0,,2py; iii, MeOH-Hf Scheme 30 Silyl ethers have been used extensively in oligonucleotide synthesis,gg affording selective protection to ribonucleoside hydroxy-functions.(ii) Cleavage. Cleavage of silyl ethers to the parent alcohols can be achieved readily in the cases of labile ethers by treatment with nucleophiles such as methanol, often with methoxide ion as catalyst. The more stable, more useful, ethers such as t-butyldimethylsilyl are cleaved by protolysis with ethanoic acid or by fluoride ion, normally as tetra-n-butylammonium fluoride, in THF;86 under such conditions fluoride ion is a strong base, so the appropriate care must be taken with base-labile substrates. (iii) Applications. Dimethyldichlorosilane and related species convert diols 95 H. 5. Schneider and R. Hornung, Annalen, 1974, 1864. 96 H. Hosoda, D. K. Fukushima, and 5. Fishman, J. Org.Chem., 1973, 38, 4209. $' I. Weisz, K. Felfoldi, and K. Kovrics, Chew. Abs., 1969, 70, 47 668. 98 E. W. Yankee, C. H. Lin, and J. Fried, J.C.S. Chem. Comrn., 1972, 1120; E. W. Yankee and G. L. Bundy, J. Amer. Chem. SOC.,1972, 94, 3651. O9 K. K. Ogilvie, E. A. Thompson, M. A. Quilliam, and J. B. Westmore, Tetrahedron Letters, 1974, 2865 and references therein; see also E. Lukevics, A. E. Zabotskaya, and I. I. Solomennikova, Russ. Chem. Rev., 1974, 43, 140; S. L. Beaucage and K. K. Ogilvie, Tetrahedron Letters, 1977, I 69 I . 36 Colvin into siliconides,100 which are analogous to acetonides; it acts as a kinetic traplol in the gibberellin-orientated pinacol cyclization shown (Scheme 3I), a complex mixture being formed in its absence.Reagents: i, Mg(Hg)-Me,SiCI, Scheme 31 Trimethylsilyl ethers are oxidized to carbonyl compoundslo2 by hydride abstraction with the triphenylmethyl cation; this has been extended to the selective oxidation of primary, secondary diols at the secondary position, though here the bistriphenylmethyl ethers are more ~uitable.10~Epoxidation of the prostaglandin (33) with alkaline hydrogen peroxide gives a mixture of cc-and p-10,ll-oxirans. Attachment of a bulky ‘remote controller’ group to the hydroxy-group at C-15 permits stereoselective epoxidation, the highest degree104 being attained with the tri-(p-xyly1)silyl derivative (34), which screens the @face of the molecule owing to the configuration of C-12; the hydroxy-group is re- generated, in this case, by reduction with aluminium amalgam (Scheme 32).(33) R = H 94 6(34) R = Si(CH,C,H,Me-p), Reagents: i, H,O,-HO-; ii, Al(Hg)-MeC0,H Scheme 32 Oxy-Cope and siloxy-Cope rearrangements of the diene (35) give quite different products (Scheme 33), in a rather dramatic demonstrationlo5 of the fact that silyl-substitution modifies the reaction course. looR. W. Kelly, Tetrahedron Letters, 1969, 967; J. Chromatog., 1969, 43, 229. lol E. J. Corey and R. L. Carney, J. Amer. Chem. SOC.,1971, 93, 7318; see also E. J. Corey,R. L. Danheiser, and S. Chandrasekaran, J. Org. Chem., 1976, 41, 260. loa M. E. Jung, J. Org. Chem., 1976, 41, 1479. lo3 M. E. Jung and L. M. Speltz, J. Amer. Chem. SOC.,1976, 98, 7882. lo4 E. J. Corey and H. E. Ensley, J.Org. Chem., 1973, 38, 3187. lo5 R. W. Thies, M. T. Wills, A. W. Chin, L. E. Schick, and E. S. Walton, J. Amer. Chem. SOC.,1973, 95, 5281 ; see also R. W. Thies and R. E. Bolesta, J. Org. Chem., 1976, 41, 1233. 37 Silicon in Organic Synthesis OR d? main I y (35) Scheme 33 Trimethylsilyloxycyclopropaneshave been involved106y lo7 in several valuable synthetic procedures, exemplified in Scheme 34. OSiMe, iv / Reagents: i, CH,I,-Zn-Cu; ii, bSph; iii, LiNR,-Me,SiCl; iv, H+ or Lewis acid; Li v, heat Scheme 34 B. Protection of Carboxylic and Sulphenic Acids.-The relative stability of silyl esters to basic and oxidizing conditions,lO* coupled with their ready cleavage on mild treatment with methanol or ethanol, makes them attractive protecting lo6 B.M. Trost and M. J. Bogdanowicz, J. Amer. Chem. Soc., 1973, 95,289, 2038; B M. Trost. and S. Kurozumi, Tetrahedron Letters, 1974, 1929. lo' C. Girard, P. Amice, J. P. Barnier, and J. M. Conia, Tetrahedron Letters, 1974, 3329. lo8See, for example, E. 5. Corey and C. U. Kim, J. Org. Chem., 1973, 38, 1233. CoIvin groups for carboxyl functions. Their use to protect the carboxy-group attached to C-3 in penicillins during the cleavage of side-chains represented an important achievementlog in devising a practical route to 6-aminopenicillanic acid (Scheme 35). Similar techniques have brought significant improvements to the prepara- tion of 7-aminocephalosporanic acid. HH HH CO,H Reagents: i, Me,SiCI-py ; ii, PC1,-py ; iii, R’OH ; iv, (NH4)HC0,-H,0 Scheme 35 The labile sulphenic acid partner in the reversible thermal rearrangement of penicillin sulphoxides can be trapped110 as the silyl ester (36), which functions as a masked RS+ species, as shown by its acid-catalysed cyclization to the cephem (37) (Scheme 36).HHPhthNhLLr3 I, PhthNv+ I 11 HH? !q OSiMe, -PhthNhi ?>-0 0 0 N/ I CO,R COzR COgR (36) (37) Reagents : i, Me,SiCI-heat ; ii, MeS0,H Scheme 36 The protected acid (38) survived two sets of reagents before liberation with methanol to give the oxepin (39)ll1 (Scheme 37). CO,SiMe, CO,SiMe, CO,H i, ii iii0 -0 -0 0 0 (38) (39) Reagents : i, N-Bromosuccinimide-CCI,-hv; ii, Et,N-Et,O ; iii, MeOH Scheme 37 loBF.M.Huber, R. C. Chauvette, and B. G. Jackson in ‘Cephalosporins and Penicillins’, ed. E. H. Flynn, Academic Press, New York, 1972, Ch. 2. 110 T. S. Chou, Tetrahedron Letters, 1974, 725; T. S. Chou, J. R. Burgtorf, A. L. Ellis, S. R. Lammert, and S. Kukolja, J. Amer. Chem. SOC.,1974, 96, 1609. J. D. Richardson, T. C. Bruice, S. M. Waraskiewicz, and G. A. Berchtold, J. Org. Chem., 1974, 39, 2088. 39 Silicon in Organic Synthesis Pyrolysis of the diester (40),followed by hydrolysis, yieldedllz the hitherto elusive butadiene-2,3-dicarboxylicacid (Scheme 38). C0,Si Me, 420 OC C0,Si Me,-M e,SiO,C C0,Si Me, Scheme 38 Sensitive and rather inaccessible acid chlorides such as 2-oxopropanoyl chloride can be prepared in good yieldl13 by the reaction of the corresponding silyl ester with oxalyl chloride. Bistrimethylsilyl malonate114J15 and alkyl trimethylsilyl ma10natesll~J~~ have found predictable utility.Trimethylsilyl oc-bromo-esters are recommended118 in the Reformatsky reaction when isolation of the P-hydroxy-acid is desired. Trimethylsilyl tribromoethanoate (41) is an effective source of dibromoketenllg (Scheme 39). The potential of the tri- methylsilyloxycarbonyl function as a nitrogen-protecting group in peptide synthesis has been explored.lZ0 Br Reagent: i, Ph,P Scheme 39 C. Protection of Alkynes and Ketens.-The use of the trialkylsilyl group to afford protection to terminal alkynes is a most active area, important contribu- tions having been made by WaltonlZ1 and co-workers, resulting in routes to lla P.Dowd and K. Kang, Synthetic Comm., 1974, 4, 151. 113 J. Hausler and V. Schmidt, Chem. Ber., 1974, 107, 145. 114 N. H. Nam, J.-P. Beaucourt, H. Hoellinger, and L. Pichat, Bull. SOC.chim. France, 1974, 1367; for conversion into carbon suboxide, see L. Birkofer and P. Sommer, Chem. Ber., 1976, 109, 1701. 116 U.Schmidt and M. Schwochau, Tetrahedron Letters, 1967, 4491. ll6 L. Pichat and J.-P. Beaucourt, Synthesis, 1973, 537. 117 B. M. Trost and R. A. Kunz, J. Org. Chem., 1974, 39, 2648. 'la A. Horeau, Tetrahedron Letters, 1971, 3227. 119 T. Okada and R. Okawara, Tetrahedron Letters, 1971, 2801. 120 Y. Yamamoto, D.S. Tarbell, J. R. Fehlner, and B. M. Pope, J. Org. Chem., 1973, 38, 2521.lZ1 R. Eastmond, T.R. Johnson, and D. R. M. Walton, Tetrahedron, 1972, 28,4601. Colvin polyalkynes,122a allene-diynes,122* and aryl-alkynes122C (Scheme 40) ; terminal substitution also allows selective oxidative transformation into carboxylic acids123 or methyl ketones.lz4 In general, protection is effected by the reaction of the alkyne anion or its equivalent with a trialkylsilyl chloride; after reaction, the terminal alkyne is liberated by hydroxide ion,125 by methanolysis, by silver(1) ion126 followed by cyanide ion,1z7 or by fluoride ion.128 iEt,Si(CEC),X + PhCICH -Ph(C=C),SiEt, R' R' \ \ Me,Si(CrC),H + C=C=CHBr C=C=CH(CrC),H R2/ /R2 Me,SiCECX + ArCu -ArCGCSiMe, R3C ECSi Me, R3CH2C0,H R3COCH3 Reagents: i, CuCI; ii, CuBr; iii, R4,BH; iv, NaOH-H,O,; v, H+-Hgz+ Scheme 40 Selective reductionl26 of non-terminal triple bonds in polyalkynes is possible if the terminal alkyne is first protected by silylation, as illustrated in the semi- hydrogenation of (42) to give a terminal Z-enyne unit in an approach129 to histrionicotoxin (Scheme 41). The Wittig salt (43), as its ylide, converts128 aldehydes into E-enyne units. The acidic hydrogen of propyne is masked by silylation, allowing preparation of the alkyl-lithium compound (44),a species used in routes to homologous lZ2(a)B.N. Ghose and D. R. M. Walton, Synthesis, 1974, 890; (b)P. D. Landor, S. R. Landor, and J. P. Leighton, Tetrahedron Letters, 1973, 1019; (c) R. Iliver and D. R. M. Walton, ibid., 1972, 5209.lZ3 G. Zweifel and S. 5.Backlund, J. Amer. Chem. Soc., 1977, 99, 3184; see also R. Koster and L. A. Hagelee, Synthesis, 1976, 118. lZ4D. A. McCrae and L. Dolby, J. Org. Chem., 1977, 42, 1607. la5 C. Eaborn and D. R. M. Walton, J. Organometallic Chem., 1966, 4, 217. la0 H. M. Schmidt and J. F. Arens, Rec. Trav. chint., 1967, 86, 1138. lZ7 E. J. Corey and H. A. Kirst, Tetrahedron Letters, 1968, 5041. lZ8E. J. Corey and R. A. Ruden, Tetrahedron Letters, 1973, 1495; E. J. Corey, G. W. Fleet, and M. Kato, ibid., 1974, 3963; see also E. Nakamura and I. Kuwajima, Angew. Chem. Internat. Edn., 1976, 15, 498. lzS A. B. Holmes, R. A. Raphael, and N. K. Wellard, Tetrahedron Letters, 1976, 1539. Silicon in Organic Synthesis OH i, ii CrC-CEC-Si Me, H H (42) .....c5H11y~\~H0c5H11+5k+ Me,SiCECCH,;Ph, Br --+111, II H H (47) H CrCH Reagents : i, H,-Pd/BaSO,-quinoline; ii, F-;iii, base Scheme 41 alkyl-alkynes,l27 oc-santalol,l30 some triterpenoids,131 and the classic synthesis of Cecropia juvenile hormone.132 The related organocopper species (45) adds 1,6 to penta-2,4-dienoate esters in a simple route133 to functionalized 1,5-enynes and 1,4,5-trienes. Me,SiCGCCH,Li R,SiC=CCH,Cu (44) (35) Bistrimethylsilylethyne reacts with acid chlorides to give134 ccp-unsaturated aldehydes (Scheme 42) by two-carbon homologation. It also undergoes a Me,SiC=CSiMe, RCOC=CSiMe, -% RCOCH,CH(OMe), iii, iv J R H HXCHO Reagents: i, RCOCl-AlC1,-CH,Cl,; ii, 0.1M-MeO-; iii, NaBH,; iv, H,O+ Scheme 42 cobalt-catalysed reaction with the diyne (46) to give the strained tetrasilyl- naphthalene (48), probably via135 the benzocyclobutene (47) (Scheme 43); 130 E.5. Corey, H. A. Kirst, and J. A. Katzenellenbogen, J. Amer. Chew. SOC.,1970, 92, 6314. 131 R. E. Ireland, M. I. Dawson, and C. A. Lipinski, Tetrahedron Letters, 1970, 2247. lS4 E. J. Corey, J. A. Katzenellenbogen, and G. A. Posner, J. Amer. Chem. SOC.,1967, 89, 4245. 133 B. Ganem, Tetrahedron Letters, 1974, 4467. 134 H. Newman, J. Org. Chem., 1973, 38, 2254. 136 R. L. Funk and K. P. C. Vollhardt, J.C.S. Chem. Comm., 1976, 833; see also K. P. C. Vollhardt and L. S. Yee, J. Amer. Chem. SOC.,1977, 99, 2010; R. L. Funk and K. P. C. Vollhardt, ibid., p. 5483. 42 CoIvin subsequent selective site-specific reaction with electrophiles (see Section 3) offers a potential route to a variety of substituted naphthalenes.J SiMe, Me,SiMe3simsiMe3 (48) Reagent: i, [CpCo(CO),] Scheme 43 Trimethylsilylketen is relatively stable, acting as a potent136 acylating agent for hindered amines and tertiary alcohols; unlike trimethylsilylbromoketen,137 it does not undergo cycloaddition reactions. The preparation (Scheme 44)and some reactions of bistrimethylsilylthioketen (49) have been described;l38 interestingly, the isomeric alkyne (50) rearranges thermally to (49). M e,SiC ECH Me,SiCGCSSiMe, (Me,Si),C=C=S (49) Reagents: i, BunLi; ii, is8;iii, Me,SiCI; iv, heat Scheme 44 7 Silyl Enol Ethers Until recently, silyl enol ethers139 were the compounds of major synthetic use of silicon, their utility being in providing regiostable, isolable species which can, R.A. Ruden, J. Org. Chem., 1974,39, 3607; for bis(trimethylsilyl)keten, see D. F. Sullivan, R. P. Woodbury, and M. W. Rathke, J. Org. Chew., 1977,42,2038. 137 W. T. Brady and R. A. Owens, Tetrahedron Letters, 1976, 1553; for (trimethylsilylrnethy1)-keten, see W. T. Brady and T. C. Cheng, J. Org. Chew., 1977, 42, 732. 13* S. J. Harris and D. R. M. Walton, J.C.S. Chem. Comm., 1976, 1008. 13y J. K. Rasmussen, Synthesis, 1977, 91. 43 Silicon in Organic Synthesis on demand, give regio-pure enolate anions140 after purification and spectral identification. They were introduced in an effort to avoid the production of an equivalent amount of base that results when metal enolates are formed from enol ethanoates or by reduction of enones with solvated electrons; the presence of such additional base encourages the formation of polyalkylated products.A. Preparation.-Silyl enol ethers are readily prepared140J41 under conditions of either kinetic or thermodynamic control (Scheme 45). OSiMe, OSiMe, i. ii -b i 00 78 22 iii. ivI-1 99 Reagents: i, Me,SiCl-Et,N-DMF-heat; ii, NaHC0,-H,O; iii, LiNPr,i-DME; iv, Me,SiCl Scheme 45 Regiospecific generation can also be achieved by trapping the enolate anion formed from an enone by conjugate reduction41c or alkylation,41b by retro- Diels-Alder fragmentation,142a or by sigmatropic rearrangement142b of /3-keto-acid silyl esters (Scheme 46).MeSi OSiM e3 + co,b Scheme 46 140 G. Stork and P. F. Hudrlik, J. Amer. Chem. Soc., 1968, 90, 4462, 4464; G. Stork, Pure Appf. Chem., 1975, 43, 553; H. 0. House, M. Gall, and H. D. Olmstead, J. Org. Chem., 1971, 36, 2361 ; H. 0. House, ‘Modern Synthetic Reactions’, 2nd edn., W. A. Benjamin, Menlo Park, California, 1972, pp. 568-569; see also R. E. Donaldson and P. E. Fuchs, J. Org. Chem., 1977, 42, 2032. 141 S. Torkelson and C. Ainsworth, Synthesis, 1976, 722; ibid., 1977, 431; G. Simchen and W. Kober, ibid., p. 259; H. Sakurai, K. Miyoshi, and Y. Nakadaira, Tetrahedron Letters, 1977, 2671 ; Y. Seki, A. Hidaka, S. Murai, and N. Sonada, Angew. Chem. Internat. Edn., 1977, 16, 174.142 (a) J. Haslouin and F. Rouessac, Bull. SOC.chim. France, 1976, 1122; (6) R. M. Coates, L. 0.Sandefur, and R. D. Smillie, J. Amer. Chem. SOC.,1975, 97, 1619. 44 Colvin An interesting method allows isolation under non-aqueous conditions (Scheme 47), low reaction temperatures favouring kinetic regio~e1ectivity.l~~ OSiMe, + Me,SiCH,CO,Et -&. 0+ CH,CO,Et Reagent: i, Bun4N+ F-Scheme 47 B. Applications.-A special feature of silyl enol ethers is their regiostability. The addition of a metal alkyl, usually methyl-lithi~rn,~~~ or of a stoicheio-metric144 or catalytic145 amount of fluoride ion, regenerates the original enolates, which are also regiostable under aprotic conditions, and undergo site-specific a1kylati0n.l~~Silyl enol ethers undergo regiospecific electrophilic substitution with strong electrophiles (Scheme 48),resulting in acylati~n,~~~~ carboxamida-tion,14@ ~ulphenylation,~~~~ conversion into en one^,^^^ sulphonylation,148 hal0genation,l4~ hydro~ylation,15~ oxirnation,l5l formation of a Mannich base,152 and azide-induced ring contraction.l53 Such en01 ethers1s4 and enol ethanoatesl55 react with carbonyl compounds, or their a~etals,l~~ in the presence of titanium@) chloride, to give /3-hydroxy- or /3-alkoxy-ketones, respectively.Similarly, Lewis-acid-catalysed Michael addition of silyl enol ethers to nitro-alkenes leads directly157 to synthetically valuable 1,4-diketones. Such diketones are also pro- 143 E. Nakamura, T. Murofushi, M.Shimuzu, and I. Kuwajima, J. Amer. Chem. SOC.,1976, 98, 2346. lP4 I. Kuwajima and E. Nakamura, J. Amer. Chem. Soc., 1975, 97, 3257. 145 R. Noyori, K. Yokoyama, J. Sakata, I. Kuwajima, E. Nakamura, and M. Shimuzu, J. Amer. Chem. SOC.,1977, 99, 1265. 146 (a) S. Murai, Y. Kuroki, K. Hasegawa, and S. Tsutsumi, J.C.S. Chem. Comm., 1972, 946; (6)I. Ojima, S. Inaba, and Y. Nagai, Tetrahedron Letters, 1973, 4271 ; Chem. Letters, 1974, 1069. IP7 E. Friedrich and W. Lutz, Angew. Chem. Internat. Edn., 1977, 16, 413. lP8 Y. Kuroki, S. Murai, N. Sonada, and S. Tsutsumi, Organometallic Chem. Synth., 1972, 1, 465. 148 R. H. Reuss and A. Hassner, J. Org. Chem., 1974,39, 1785 ;L. Blanco, P. Amice, and J. M. Conia, Synthesis, 1976, 194; see also M.Zembayashi, K. Tamao, and M. Kumada, ibid., 1977, 422. 150 A. G. Brook and D. A. Macrae, J. Organometallic Chem., 1974,77, (219; G. M. Rubottom, M. A. Vazquez, and D. R. Pelegrina, Tetrahedron Letters, 1974, 4319; G. M. Rubottom, J. M. Gruber, and G. M. Mong, J. Org. Chem., 1976, 41, 1673; for the related preparation of a-hydroxy-acids, see G. M. Rubottom and R. Marrero, ibid., 1975,40, 3783. lS1 J. K. Rasmussen and A. Hassner, J. Org. Chem., 1974, 39, 2558. lS2 S. Danishefsky, T. Kitahara, R. McKee, and P. F. Schuda, J. Amer. Chem. SOC.,1976, 98, 6715; see also N. L. Holy and Y. F. Wang, ibid., 1977, 99, 944; W. Oppolzer, H. Hauth, P. Pfaffli, and R. Wenger, Helv. Chim. Acta, 1977, 60, 1801. lS3 R. A. Wohl, Helv. Chirn. Acta, 1973, 56, 1826; Tetrahedron Letters, 1973, 31 11.154 T. Mukaiyama, K. Narasaka, and K. Banno, Chem. Letters, 1973, I01 1; T. Mukaiyama, K. Banno, and K. Narasaka, J. Amer. Chem. Soc., 1974, 96, 7503; E. Nakamura and I. Kuwajima, ibid., 1977, 99, 961. lS5 T. Mukaiyama, T. Izawa, and K. Sago, Chem. Letters, 1974, 323. lS6 T. Mukaiyama and M. Hayashi, Chem. Letters, 1974, 15. lS7 M. Miyashita, T. Yanami, and A. Yoshikoshi, J. Amer. Chem. SOC., 1976, 98, 4679. 45 Silicon in Organic Synthesis duced by oxidative coupling158 of enol ethers by silver@), good yields of cross-coupled products being obtainable. a-Trimethylsilyl esters react with fluoride ion,l59 giving ester enolates, which 0 CONHR t bSPh 0 OH 0 J ooHI 0 Reagents: i, RCOCl; ii, RNCO-Et,N; iii, PhSCl; iv, lo2;v, Ph,P; vi, RSOzCI; vii, X2; viii, m-chloroperbenzoic acid; ix, NOCl; x, CH,=NfMe2 I-; xi, ArSO,N,; xii, R1COR2-TiCll ; xiii, \\f and TiCI,; xiv, A&O-DMSO NO2 Scheme 48 158 Y.Ito, T.Konoika, and T. Saegusa, J. Amer. Chem. SOC.,1975,97,649; for similar dimeric coupling of esters, see S. Inaba and 1. Ojima, Tetrahedron Letters, 1977, 2009. 159 E. Nakamura. M. Shimuza, and 1. Kuwajima, Tetrahedron Letters, 1976, 1699. 46 Colvin condense with carbonyl compounds to give protected p-hydroxy-esters (Scheme 49). R2 iMe,SiCH,CO,R' + R2COR3 -\co2R' R3 OSiMe, Reagent: i, R4, N+ F-Scheme 49 Silyl enol ethers, as electron-rich alkenes, can be smoothly and selectively ozonizedl60 (Scheme 50).They also react readily with Simmons-Smith reagents,161 Reagents: i, 0,-MeOH; ii, NaBH,; iii, H,O+ Scheme 50 leading initially to cyclopropanol silyl ethers.162 Conia163 has described the selective ct-or or'-methylation of steroidal ctp-unsaturated ketones (Scheme 51) ; when cisoid or labile enones are involved, an alternative course164 of ring opening occurs, leading to cyclobutanones and cyclopentanones as shown in Scheme 34. Simmons-Smith addition to cyclic silyl enol ethers in concentrated solution results in zinc-iodide-induced isomerizationl65 of the initially formed cyclopropyl ethers to protected 2-methylenecycloalkanols (Scheme 52). Ally1 esters, as their corresponding silyl keten acetal~,l~~J~~ undergo [3,3 ]-sigmatropic rearrangement to protected @-unsaturated acids (Scheme 53).The use of t-butyldimethylsilyl chloride as the enolate trap is recommended, looR. D. Clark and C. H. Heathcock, Tetrahedron Letters, 1974, 1713, 2027; J. Org. Chem., 1976, 41, 1396. lB1 J. M. Denis and J. M. Conia, Tetrahedron Letters, 1972,4593; I. Ryu, S. Murai, S. Otani, and N. Sonoda, Chem. Letters, 1976, 93; Y. Ito, S. Fujii, and T. Saegusa, J. Org. Chcm., 1976, 41, 2073. lBaFor a full review, see J. M. Conia, Pure Appl. Chem., 1975, 43, 317. 163 C. Girard and J. M. Conia, Tetrahedron Letters, 1974, 3327; for a related route to a-halo- geno-np-unsaturated carbonyl compounds, see P. Amice, L. Blanco, and J. M. Conia, Synthesis, 1976, 196. 184 J. Salaun, B. Garnier, and J. M.Conia, Tetrahedron, 1974, 30, 1413. lB5 S. Murai, T. Aya, T. Renge, I. Ryu, and N. Sonoda, J. Org. Chem., 1974, 39, 858; I. Ryu, S. Murai, S. Otani, and N. Sonoda, Tetrahedron Letters, 1977, 1995; for conversion into p-bromo-ketones, see S. Murai, Y. Seki, and N. Sonoda, J.C.S. Chem. Comm., 1974, 1032. lB8R. E. Ireland, R. H. Mueller, and A. K. Willard, J. Amer. Chem. Soc., 1976, 98, 2868; J. Org. Chem., 1976, 41, 986. 16' J. Boyd, W. Epstein, and G. Frater, J.C.S. Chem. Comm., 1976, 380. 47 Silicon in Organic Synthesis Me,SiO a] L'%-Me3SiOa] &-OQ} ii, iii\y Me,SiO Reagents: i, Et,N-Me,SiCl-DMF; ii, LiNPr',; iii, Me,SiCI; iv, CH,I,-Zn-Ag; v, MeOH-Hf Scheme 51 r OSiMe, OSiMe, Reagents : i, CH,I,-Zn-Cu (concentrated solution) Scheme 52 permitting stereoselective formation and isolation166 of the acetals prior to rearrangement ; triethylsilyl chloride has also been advocated.l68 The syntheses and pyrolyses of keten alkyl trimethylsilyl and bistrimethylsilyl R+i+,Rl I, ,.Ra,&,Rl R2 & R', I1 R' R2oe R3R3 R3 0 OSi Me,But OSiMe,But Reagents: i, LiNPr',; ii, ButMe2SiC1,iii, heat Scheme 53 ld8W. C. Still and M. J. Schneider, J. Anter. Chem. SOC.,1977, 99, 948. Colvin acetals (51) have been described;169 the latter compounds provide a route to p-keto-acids (Scheme 54) ; 0-t-butyldimethylsilyl keten acetals such as (52) are valuable equivalents of ester en01ates.l~~ R,CHCO,H i ii iii, iv + R,CHCOCR,COIH/OSiMe3R,C=C \ OSiMe, * + RCOCl --!&RCOCH,CO,Et OEt Reagents: i, LiNPr',; ii, Me,SiCI; iii, heat; iv, H,O+; v, Et,N Scheme 54 The trimethylsilyloxybuta-1,3-dienes(53),171 (54),172 (55),173 and (56)174 have been used as 457components in Diels-Alder cycloadditions, silyl enol ether masking being preferred to the alternative alkyl enol ethers or enol ethanoates.OSiMe, Me3SiOjeph Me,SiO OMe (54) (53) Metallated allyloxy-silanes (57) behave175 as P-acyl carbanion equivalents (Scheme 55); metallated ally1 alkyl ethers176 show similar properties. The sym- 16* C. Ainsworth, F. Chen, and Y.-N. Kuo, J. Organometallic Chem., 1972, 46, 59; C. Ains-worth and Y.-N. Kuo, ibid., p. 73. 170 M. W. Rathke and D. F. Sullivan, Synthetic Conim., 1973, 3, 67; Tetrahedron Letters, 1973, 1297.S. Danishefsky, C. F. Yan, and P. M. McCurry, J. Org. Chem., 1977, 42, 1819; see also S. Danishefsky, T. Kitahara, P. F. Schuda, and S. J. Etheredge, J. Artier. Chem. SOC., 1976, 98, 3028; 5. F. W. Keana and P. E. Eckler, J. Org. Chem., 1976,41,2850. 172 M. E. Jung and C. A. McCombs, Tetrahedron Letters, 1976, 2935. 173 T. Ibuka, Y. Mori, and Y. Inubushi, Tetrahedron Letters, 1976, 3169. G. M. Rubottom and D. S. Krueger, Tetrahedron Letters, 1977, 61 1 ;G. M. Rubottom and J. M. Gruber, J. Org. Chem., 1977, 42, 1051. 175 W. C. Still and T. L. Macdonald, J. Amer. Chem. SOC.,1974, 96, 5561 ; with carbonyl compounds as electrophiles, exclusive a-attack is observed: J. Org. Chem., 1976, 41, 3620. 176 D. A. Evans, G.C. Andrews, and B. Buckwalter, J. Amer. Chem. Soc., 1974, 96, 5560. 49 Silicon in Organic Synthesis metrical anion (58) is an equivalent177 for the hypothetical homoenolate anion of ethyl vinyl ketone, undergoing electrophilic attack at mainly the y-position. Me,SiO-Li ii. iii-[ ] -R Me,SiO -cHO Li+ .. ...TL-% RwOSiEt, OSiEt, 0 (58) Reagents: i, BusLi; ii, RX; iii, H,O+ Scheme 55 Acetonides, including the hitherto unknown acetonide of trans-cyclohexane- 1,2-diol, are readily prepared178 from 2-trimethylsilyloxypropeneand 1,2-diols (Scheme 56). Scheme 56 C. Acyloin Trapping and Reductive Cleavage.-The enolate anion intermediates in the acyloin condensation179 can be trapped by silylation, preventing180 the condensation and polymerization which often complicate this route to cyclic or-hydroxy-ketones. The resulting bis-silyl enol ethers are readily hydrolysed or oxidized,lal allowing the preparation of, inter alia, cyclobutanedionels2 (Scheme 57), all attempts to oxidize the readily accessible oc-hydroxycyclo- butanone having failed.W. Oppolzer and R. L. Snowden, Tetrahedron Letters, 1976, 4187. lV8G. L. Larsen and A. Hernandez, J. Org. Chem., 1973, 38, 3935. l7# I.J. Bloomfield, D. C. Owsley, C. Ainsworth, and R. E. Robertson, J. Org. Chem., 1975, 40, 393. lSo K. Ruhlmann, Synthesis, 1971, 263. lS1 T. Kowar and E. LeGoff, Synthesis, 1973, 212; J. Strating, S. Reiffers, and H. Wynberg, ibid., 1971, 209; for the alkylation of the derived lithium 1,2-enediolates, see T.Waka-matsu, M. Fukui, and Y. Ban, ibid., 1976, 341; for their conversion into alkynes, see D. P. Bauer and R. S. Macomber, J. Org. Chem., 1976, 41, 2640. lapH.-G. Heine, Chem. Ber., 1971,104,2869; J. M. Conia and J. M. Denis, Tetrahedron Letters, 1971,2845; see also H.-G. Heine and D. Wendisch, Annalen, 1976,463. Colvin Reagents: i, Na-PhMe-Me,SiCl; ii, Br, Scheme 57 Under certain conditions, 1,2-diesters undergo reductive cleavage of the connecting o-bond. An extension to provide a method for the introduction of ethanoic acid fragments has also provided evidence183 for the mechanism of this reaction, which appears to proceed as shown in Scheme 58. The com- petitiveness and solvent dependence of these two reductive processes are seen in the acyloin condensation184 of (59) and the o-cleavage183 of (60).r 1 C0,Me OSiMe, OSiMe, C0,Me OMe I C0,Me C0,Me Reagents: i, 2e-; ii, Me,SiCI; iii, Na-PhMe-Me,SiCI; iv, H,O+; V, Na-NH, Scheme 58 183 P. G. Gassman and X. Creary, J.C.S. Chem. Comm., 1972, 1214. la4 M. E. Jung, J.C.S. Chem. Comm., 1974, 956. Silicon in Organic Synthesis 8 Activation/Protection of Nitrogen After the halogeno-silanes, amino-silanes are the next most reactive class of organosilane in which silicon is bonded to a more electronegative element; the silicon-nitrogen bond is readily ~leaved~9~ (Scheme 59). This section will explore the fate of the nitrogen moiety. \ \ /-Si---N / + E-Nu-d -Si-Nu + E-N /\ / \ Scheme 59 N-Trimethylsilyl secondary amines are recommended185 for easy formation of enamines.Acid halides react readily with amino-silanes, providing a now standard method4$6 for amide (peptide) bond formation. The silylated amines are normally more reactive than the parent compounds, and the co-produced silyl halide or equivalent plays no further part in the reaction. It is not normally possible to convert an inactive, ester-protected acid directly and non-hydrolytically into an activated acid derivative under mild conditions.186 Ma~amunel~~reasoned (Scheme 60) that, if R1O- could be removed by reaction with MY, M+ being a relatively hard acid (with a strong affinity for oxygen), and Y-being a relatively soft base, then such a desirable sequence might become feasible.Both phenyl and trichloroethyl esters have an acceptable degree of stability, yet are rapidly converted into acid imidazolides by treatment with N-trimethylsilylimidazole. Nitrile a-anions react with trimethylsilyl chloride to give, as expected, a-silyl-nitriles. If, however, t-butyldimethylsilyl chloride is employed, the anions are trapped in their ketenimine form; this results in an efficient method188 for the oxidative decyanation of secondary aralkyl- and diaryl-nitriles (Scheme 61). A wide range of Grignard reagents react with trimethylsilyl isocyanate (61) to give homologous primary amides ;lag the silylated aminocopper compound (62) converts aryl iodides into primary amineslgO in modest yield. 9 Silicon-substituted Bases Lithium,lgl sodiurn,lg2 and potassium193 bistrimethylsilylamide (Scheme 62) have all found extensive use as strong, non-nucleophilic bases.lES R. Comi, R. W. Franck, M. Reitano, and S. M. Weinreb, Tetrahedron Letters, 1973, 3107; but see L. H. Hellberg and A. Juarez, ibid., 1974, 3553. lE6See, however, A. G. Anderson and D. H. Kono, Tetrahedron Letters, 1973, 5121 ; D. J. Burton and W. F. Koppes, J.C.S. Chem. Comm., 1973,425. lE7G. S. Bates, J. Diakur, and S. Masamune, Tetrahedron Letter$, 1976, 4423. lE8 D. S. Watt, J. Org. Chern., 1974,39,2799; S. J. Selikson and D. S. Watt, Tetrahedron Letters, 1974, 3029. K. A. Parker and E. G. Gibbons, Tetrahedron Letters, 1975, 981 ; see also P. Bourgeois, G. Merault, and R. Calas, J.Organometallic Chern., 1973, 59, C4. lS0 F. D. King and D. R. M. Walton, J.C.S. Chem. Comm., 1974, 256; Synthesis, 1976, 40; see also T. Tsuda, H. Washita, and T. Saegusa, J.C.S. Chem. Comm., 1977, 468. lgl E. H. Amonoo-Neizer, R. A. Shaw, D. 0. Skovlin, and B. C. Smith, J. Chem. Soc., 1965, 2997. lg2 U. Wannagat and H. Niederpriim, Chem. Ber., 1961, 94, 1540; U. Wannagat, Pure Appl. Chem., 1969, 19, 329. lg3 C. A. Brown, Synthesis, 1974, 427. Colvin R'C + Y--=RIC + R20-\ \ OR2 k Y \ \ \ \ \ \ \ \ \ R20-+ MY RzOM + Y-95 % Reagent: i, PhO- (catalytic) Scheme 60 Ar\C/CN R' 'SiMe, Ar CN i \/+ /*R' \H Ar\ C -C =NSiMe,But R' Ar V Ar \/"f--R R / \x Reagents: i, LiNPr',; ii, Me,SiCl; iii, ButMe,SiCl; iv, I,, Br2, or PhSCl; v, HsO+ Scheme 61 Me,Si N CO (M e,Si),NCu (61) (62) i, ii, or iii (Me,Si),NH (Me,Si),NM Reagents: i, BunLi; ii, NaNH,; iii, KNH, Scheme 62 Silicon in Organic Synthesis The lithium amide is recomrnendedlg4 for the generation of kinetic enolates (Scheme 63); the sodium amide can also be used,195 but the resulting enolates are, as expected, less regiostable.Reagents: i, LiN(SiMe,),; ii, Me1 Scheme 63 With dienones, the y-rather than the €-proton is removed,l96 to give cross- conjugated enolate anions (Scheme 64). Reagents: i, LiN(SiMe,),; ii, electrophile Scheme 64 The lithium amide is also the preferredlg7 base in Darzens condensations, allowing the use even of ethanal as electrophile.The sodium amide has been advantageously employed in Dieckmann condensations198 of ccw-diesters, especially in those cases where additional nucleophilically labile groups are present. It is also recommendedlg9 for the convenient generation of monobromo- and monochloro-carbenes from the corresponding dihalogenomethanes. Intramolecular displacement of halide ions from halogeno-acetals provides a synthesis2Oo (Scheme 65) of functionalized bicyclic diketones; when the lithium amide is used as a base, the product is 95% trans-(63), whereas, remarkably, if the metal ion is potassium, the stereochemistry is completely reversed, giving 95 % cis-(63). Cyclizations involving attack by a carbanion on an electrophile usually result in the formation of a five- rather than of a six-membered ring, and rarely a four-membered ring.Stork201 has reported a process of ‘epoxynitrile cyclization’, lS4 M. Tanabe and D. F. Crowe, J.C.S. Chem. Comm., 1973, 564. lS5 D. H. R. Barton, R. H. Hesse, G. Tarzia, and M. M. Pechet, Chem. Cornm., 1969, 1497; M. Tanabe and D. F. Crowe, ibid., p. 1498. leeH. Hart, G. M. L,ove, and I. C. Wang, Tetrahedron Letters, 1973, 1377. R. F. Borch, Tetrahedron Letters, 1972, 3761 ;but see G. Kyriakakou and J. Seyden-Penne, ibid., 1974, 1737. R. N. Hurd and D. H. Shah, J. Org. Chem., 1973, 38, 390. lS9B. Martel and J. M. Hiriart, Synthesis, 1972, 201. G. Stork, J. 0. Gardner, R. K. Boeckman, and K. A. Parker, J. Amer. Chem. SOC.,1973, 95, 2014; G. Stork and R.K. Boeckman, ibid., p. 2016. G. Stork, L. D. Cama, and D. R. Coulson, J. Amer. Chem. SOC.,1974, 96, 5268. Colvin Br Br Reagent: i, LiN(SiMe,), or KN(SiMe,), Scheme 65 in which these tendencies are reversed (Scheme 66); these reversals are ascribed to the geometric constraints imposed by the oxiran ring in each case, making it difficult for the nitrile anion and the oxiran C-0 bond to come into line for formation of a five-membered ring. The second reaction shown is highly stereo- selective, and has been employed202 in a synthesis of ( & )-grandis01 (64). OH 0 Reagent: i, NaN(SiMe,), Scheme 66 Lithium 1 ,l-bistrimethylsilyl-3-methylbutoxide(65) is an exceptionally hindered strong base;203 it regiospecifically removes methyl protons from ethanoates2wU and methyl ketones,204b even in the simultaneous presence of aldehydes, which then trap the enolate anions and provide a new range of regio- specific aldol condensations (Scheme 67).202 G. Stork and I.F. Cohen, J. Amer. Chem. SOC.,1974, 96, 5270. 203 I. Kuwajirna. T. Sato, N. Minarni, and T. hbe, Terrahedron Letters, 1976, 1591 ; I. Kuwa-jirna, M. Arai, and T. Sato, J. Amer. Chem. SOC.,1977, 99, 4181. 204 (a) I. Kuwajirna, N. Minarni, and T. Sato, Tefrahedron Letters, 1976, 2253; see also N. Minarni and I. Kuwajirna, ibid., 1977, 1423; (6) I. Kuwajima, T. Sato, M. Araki and N. Minarni, ibid., 1976, 1817. 55 Silicon in Organic Synthesis SiMe, I Me,CHC H ,C-OLiI SiMe, OH (65) IRTHO + MeCOR2 4 R1CHCH,COR2 R2 = CH,R or OR Scheme 67 Trimethylsilylpotassium is recommendedzo5 for the metallation of vinylic, allylic, and benzylic substrates.10 Silanes as Reducing Agents The addition of the Si-H linkage to unsaturated substrates is important not only as a method of reduction but also as a major route to complex organo- silanes. Such additions can be brought about under catalytic or ionic conditions. A distinctly different method of reduction uses trimethylsilyl chloride-metal systems. A. Catalytic Reduction.-Silanes will reduce a wide variety of functional groups under catalysis ,by transition metals. Alkynes undergo cis-addition,206 with the terminal regiospecificity shown (Scheme 68) ;peroxide initiation yields the trans- isomer, and nickel(i1) catalyses a double addition.207 Whereas the catalysed addition of trialkylsilanes to ketones gives silyl ethers,208 xP-unsaturated ketones react by a process of 1 ,4-addition20g to give silyl enol ethers (Scheme 69); only conjugated double bonds are affected.Asymmetric hydrosilylationzlo of either class of substrate can be achieved using chiral catalysts. Carboxylic acid chlorides are reduced2I1 to aldehydes (Scheme 70) in an alternative to the Rosenmund reduction; yields are lower if there is cc-branching. 205 J. Hartmann and M. Schlosser, Helv. Chim. Acta, 1976, 59, 453; M. Schlosser and J. Hartmann, J. Amer. Chem. SOC., 1976, 98, 4674; M. Stahle, J. Hartmann, and M. Schlosser, Helv. Chim. Acta, 1977, 60, 1730. 206 R.A. Benkeser, M. L. Burrous, L. E. Nelson, and J. V. Swisher, J. Amer. Chem. SOC., 1961, 83,4385. 207 K. Tamao, N. Miyake, Y. Kiso, and M. Kumada, J. Amer. Chem. SOC.,1975, 97, 5603. 208 I. Ojima, M. Nihonyanagi, and Y. Nagai, J.C.S. Chem. Comm., 1972, 938. 209 T. Ojima, T. Kogure, and Y. Nagai, Tetrahedron Letters, 1972, 5035. 210 H. B. Kagan, Pure Appl. Chem., 1975,43,401;T. Hayashi, K. Yamamoto, and M. Kumada, Tetrahedron Letters, 1975, 3; I. Ojima, T. Kogure, and M. Kumagai, J. Org. Chem., 1977, 42, 1671. 211 5. D. Citron, J. Org. Chem., 1969,34, 1977; see also S. P. Dent, C. Eaborn, and A. Pidcock, Chem. Comm., 1970, 1703. 56 Colvin R\?RC=CR -/"="\H Six, R H \RCECH ?="\/ H Six, R R \/RCGCR -/"=c\ X,Si Six, Reagents: i, X,SiH-H,PtCI,; ii, X,SiH-NilI Scheme 68 Reagents: i, R,SiH-Rh* catalyst Scheme 69 RCOCl RCHO Reagents: i, Et,SiH-Pd Scheme 70 Imines are reduced212 to amines, again with potential chirality,213 in what is claimed to be the best method of reduction of such compounds (Scheme 71).Pyridines undergo 1,4-addition to give N-silyl species, which can be converted into the parent 1 ,4-dihydropyridines214 by controlled hydrolysis. Commercially available polymethylhydrosiloxane (66), in the presence of an organotin catalyst in a protic solvent, functions215 as a mild reagent for the 212 I. Ojima, T. Kogure, and Y. Nagai, Tetrahedron Letters, 1973, 2475. 213 N. Langlois, T.-P. Dang, and H. B. Kagan, 7'etrahedron Letters, 1973, 4865.214 N. C. Cook and J. E. Lyons, J. Amer. Chem. SOC.,1965, 87, 3283. 215 J. Lipowitz and S. A. Bowman, J. Org. Chem., 1973, 38, 162. 57 Silicon in Organic Synthesis )=” Reagents: i, R’,SiH-Rh* catalyst; ii, MeOH; iii, R2COCl Scheme 71 selective reduction of aldehydes and ketones to carbinols (Scheme 72), the catalyst providing a tin hydride as the active reducing agent. In the presence of Pd/C, alkenes and nitro-groups are smoothly reduced. Primary and secondary alcohol chloromethanoates are reduced to the corresponding alkanes by radical- induced reaction216 with tri-n-propylsilane. Reagents : i, (R,Sn),O-EtOH Scheme 72 The combination of trichlorosilane and tertiary amines217 reduces a range of aromatic carbonyl compounds, including acidP* (Scheme 73), to hydro- carbons: such a system also reduces phosphine oxides to phosphines219 with retention of configuration ;similar deoxygenation can be achieved with trichloro- silane220 or phenylsilane221 alone.C0,Et C02Et C02Et Reagents: i, C1,SiH-Et,N; ii, KOH-EtOH Scheme 73 N. C. Billingham, R. A. Jackson, and F. Malek, J.C.S. Chern. Comm., 1977, 344; see also M. G. Adlington, M. Orfanopoulos, and I. L. Fry, Tetrahedron Letters, 1976, 2955; M. P. Doyle, C. C. McOsker, and C. T. West, J. Org. Chem., 1976, 41, 1393. R. A. Benkeser, Accounts Chem. Res., 1971, 4, 94. a18 R. A. Benkeser and D. F. Ehler, J. Org. Chem., 1973, 38, 3660; see also G. S. Li, D. F. Ehler, and R. A. Benkeser, Org. Synth., 1973, 53, 159.21s C. R. Hall and D. J. H. Smith, Tetrahedron Letters, 1974, 1693. 2eo Y. Segall, I. Granoth, and A. Kalir, J.C.S. Chew. Comm., 1974, 501. K. L. Marsi, J. Org. Chem., 1974, 39, 265. Coivin B. Ionic Hydrogenation.-This system (Scheme 74) involves the stepwise addition to the substrate of H+ and H-, the most efficient reagent combination222 being trifluoroethanoic acid-triethylsilane. The procedure has been extensively explored and detailed,223 and will definitely find increasing use. H-\ -C-YH /IH \ H+ \;/ H-\-c-x ---HX/ I Scheme 74 Reduction of nitrilium ions by silane produces aldimines,224 and thence alde- hydes (Scheme 75), complementing the known method for reduction of such ions to amines by using borohydride.RCH,NHEt I + 7 RCN -RCzNEt BF,-.\ 111, 1v RCHO Reagents: i, Et,O+ BF,-; ii, NaBH,; iii, Et,SiH; iv, H,O+ Scheme 75 C.Chlorosilane-Metal Systems.-This area has been thoroughly investigated by French workers, who have reviewed225 their progress. The reagent system most commonly used, trimethylsilyl chloride-magnesium-hexamethylphosphor-amide, probably involves a silyl Grignard reagent, which, on reaction with a range of ctp-unsaturated ketones226 and ester~,22~ causes reductive dimerization, producing 1,4-dicarbonyl compounds in synthetically useful yields (Scheme 76). Benzene is converted into cyclohexa-l,4-diene in moderate yield by a reducing system consisting of lithium and trimethylsilyl chloride228 (Scheme 77). 222 M.P. Doyle, D. J. DeBruyn, S. J. Donneliy, D. A. Kooistra, A. A. Odubela, C. T. West, and S. M. Sonnebelt, J. Org. Chem., 1974, 39, 2740. 223 D. N. Kursanov, Z. N. Parnes, and N. M. Loim, Synthesis, 1974, 633. 22p J. L. Fry, J.C.S. Chem. Comm., 1974, 45. 225 R. Calas and J. Dunogues, ref. 2, Vol. 2, p. 277. 226 J. Dunogues, R. Calas, M. Bolourtchian, C. Biran, and N. Duffaut, J. Organometalfic Chem., 1973,57,55. 227 J.-P. Pichard, J. Dunogues, and R. Calas, J. Organometallic Chem., 1974, 77, 167. 228 J. Dunogues, R. Calas, and N. Ardoin, J. Organometallic Chem., 1972, 43, 127; see also L. Birkofer and N. Ramadan, Chem. Bet-., 1971, 104, 138. 59 Silicon in Organic Synthesis 65 % Reagents: i, Me,SiCl-Mg-HMPA, FeCI, or TiCl, catalyst; ii, MeOH Scheme 76 SiMe, I SiMe, 55 'I; Reagents: i, Li-Me,SiCI-THF; ii, KOH Scheme 77 11 Trimethylsilyl Cyanide Trimethylsilyl cyanide is a potent agent for effecting cyanide tran~fer,~~9-23~ aldehydes, ketones, and @-unsaturated carbonyl systems all reacting smoothly with the reagent in the catalytic presence of Lewis acids233 or crown-ether- solubilized potassium cyanide (Scheme 78).Its use permits an efficient and reliable synthesis234a of P-aminomethyl alcohols, including those from ketones which do not form stable cyanohydrins, and those from conjugated en0nes,234~ where clean 1,Zaddition is observed. Aryl and heteroaryl aldehydes can be converted232 into ketones, as shown in Scheme 78. Cyanosilylation of p-benzoquinones not only affords a degree of protection to the quinone system, but also provides a new synthesis234c of quinols (Scheme 79).229 D. A. Evans, L. K. Truesdale, and G. L. Carroll, J.C.S. Chem. Cumm., 1973, 55. 230 W. Lidy and W. Sundermeyer, Chem. Ber., 1973, 106, 587. 231 H. Neef and R. Muller, J. prakt. Chem., 1973, 315, 367. 232 K. Deuchert, U. Hertenstein, and S. Hunig, Synthesis, 1973, 777. 233 D. A. Evans and L. K. Truesdale, Tetrahedron Letters, 1973, 4929; for an alternative pre- paration of the reagent, see J. W. Zubrick, B. I. Dunbar, and H. D. Durst, ibid., 1975, 71. 234 (a)D. A. Evans, G. L. Carroll, and L. K. Truesdale, J. Org. Chem., 1974,39,914; (0)for the alkylation of the anions derived from such unsaturated cyanohydrins, see U.Hertenstein, S. Hunig, and M. Oller, Synthesis, 1976, 416; (c) D. A. Evans, J. M. Hoffman, and L. K. Truesdale, J. Amer. Chem. Suc., 1973, 95, 5822; for improved procedure and application, see D. A. Evans and R. Y. Wong, J. Org. Chem., 1977, 42, 350. 60 Colvin R‘ \ RL\C/OSiMe3C=O + Me3SiCN _.)/ RZ R2’ ‘CN Il-IV R’ Reagents: i, LiAlH,; ii, LiNPri2; iii, R3X; iv, H30+ Scheme 78 0 0 6 0 Reagents: i, Me,SiCN<atalyst; ii, AgF; iii, RMgX or RLi Scheme 79 The analogous carbonyl-insertion properties of ethyl trimethylsilyldiazo- ethan0ate,~35~ and mixed tervalent phosphorus-organosiliconthiosilane~,~~s~ reagents235c have been delineated. 12 Trimethylsilyl Azide Trimethylsilyl a~ide2~~ is preferable to the highly explosive hydrazoic acid for the synthesis of 1,2,3-triazole~~~~ (Scheme 80) and related238 heterocyclic systems, the silyl group in the products being hydrolytically labile.It complements sodium azide in such cycloadditions, working best with electron-rich alkynes ; azide ion is more effective with electron-poor substrates. It is also preferable239 to aryl sulphonyl azides for the preparation of aziridines. The reagent converts acid chlorides and anhydrides into acid azides prior to Curtius rearrangement to isocyanates;240 it also converts halogeno-ethanoates 235 (a) D. A. Evans, L. K. Truesdale, and K. G. Grimm, J. Org. Chem., 1976, 41, 3335; (b) D. A. Evans, L. K. Truesdale, K. G. Grimm, and S. L. Nesbitt, J. Amer. Chem. Soc., 1977, 99, 5009; (c) D.A. Evans, K. M. Hurst, L. K. Truesdale, and J. M. Takacs, Tetra-hedron Letters, 1977, 2495. 236 L. Birkofer and P. Wegner, Org. Synth., 1970, 50, 107; see also S. S. Washburne and W. R. Peterson, J. Organometallic Chem., 1971, 33, 153. 237 Y.Tanaka, S. R. Velen, and S. 1. Miller, Tetrahedron, 1973, 29, 3271. 238 E. Ettenhuber and K. Ruhlmann, Chem. Ber., 1968, 101, 743. 239 K. Wiesner, Chemical Society Centenary Lecture, Glasgow, 1977 (Chem. SOC.Rev., 1977, 6, 413). 240 S. S. Washburne and W. R. Peterson, Synthetic Conim., 1972, 2, 227; S. S. Washburne, W. R. Peterson, and D. A. Berman, J. Org. Chem., 1972, 37, 1738; J. H. MacMillan and S. S. Washburne, ibid., 1973, 38, 2982. Silicon in Organic Synthesis R R RC=CR Reagents: i, Me,SiN,; ii, H,O Scheme 80 into a~ilo-ethanoates,~4~which are precursors to alkoxycarbonylnitrenes (Scheme 81).(RCO),O RCOCl \ N3 Reagent: i, Me,SiN, Scheme 81 Trimethylsilyl azide, in combination with lead(1v) ethanoate or iodobenzene diethanoate, reacts with alkenes to give a variety of pr0ducts.2~2 The latter, milder, reagent combination converts243 cyclic alkenes into a-azido-ketones ; enol ethers and other electron-rich alkenes, on the other hand, undergo regio- specific cleavage (Scheme 82). I 4R)&R0R+ R I e*g* 0+ ON3 R X 1 \dRwx CN + O=c / R k CN 1 A0 10 Reagents: i, PhI(OAc),-Me,SiN, Scheme 82 241 H. R. Kricheldorf, Synrhesis, 1972, 695. 242 E. Zbiral, Synthesis, 1972, 285.243 J. Ehrenfreund and E. Zbiral, Annalen, 1973, 290. 62 Colvin 13 Miscellaneous A major area of application of trialkylsilyl groups utilizes their extreme bulk to provide ligands capable of stabilizing metals in low-co-ordinative environ- ments; this area has been extensively reviewed.244 A recent example245 can be seen in the first preparation of stable two-co-ordinate phosphorus- and arsenic- centred radicals, (67) and (68). A related use of such bulky substituents has allowed the preparation and conformational st~dy24~ of relatively long-lived carbon radicals such as (69). [(Me,Si),CH], M' [( Me,Si),N], M -(67) M = P or As (68) M = P or As (Me,Si),kH(SiMe,), (69) t, (50°C) = 120 h Tertiary propynyl alcohols rearrange247 smoothly in the presence of polymeric silyl vanadates to @-unsaturated aldehydes (Scheme 83).R' R' C=CH -&-R' CHO Reagent: i, -(Ph,SiOV=O)n, heat I Scheme 83 Trimethylsilyl iodide converts248 esters into the corresponding labile silyl esters, and thence into the acids, probably by the process shown in Scheme 84. No selectivity is seen with simple esters, although it may be possible to cleave t-butyl and benzyl esters selectively. Trimethylsilyl bromide cleanly dealkylate~~*~ phosphonic acid dialkyl esters under mild conditions. 244 D. H. Harris and M. F. Lappert, ref. 2, Vol. 2, p. 13; D. C. Bradley and M. H. Chisholm, Accounts Chem. Res., 1976, 9, 273. 245 M. J. S. Gynane, A. Hudson, M. F. Lappert, P. P. Power, and H. Goldwhite, J.C.S.Chem. Comm., 1976, 623. 246 D. Griller and K. U. Ingold, J. Amer. Chem. SOC., 1974, 96, 6203; Accounts Chem. Res., 1976, 9, 13. 2*7 H. Pauling, D. A. Andrews, and N. C. Hindley, Helv. Chim. Acta, 1976, 59, 1233; G. L. Olson, K. D. Morgan, and G. Saucy, Synthesis, 1976, 25; M. B. Erman, I. S. Aul'chenko, L. A. Kheifits, V. G. Dulova, Yu. N. Novikov, and M. E. Vol'pin, Tetrahedron Letters, 1976, 2981. 248 M. E. Jung and M. A. Lyster, J. Amer. Chem. SOC., 1977, 99, 968; T.-L. Ho and G. A. Olah, Angew. Chem. Internat. Edn.,1976, 15, 774; Synrhesis, 1977, 417; for the conversion of alcohols into iodides using this reagent, see M. E. Jung and P. L. Ornstein, Tetrahedron Letters, 1977, 2659. *IsC. E. McKenna, M. T. Higa, N. H. Cheung, and M. C. McKenna, Tetrahedron Lefters, 1977, 155.63 Silicon in Organic Synthesis Scheme 84 14 Concluding Remarks It is to be hoped that this short review has given some indication of the excep- tional utility of silicon in synthetic organic chemistry; space does not permit discussion of its applicability elsewhere, which is equally impressive, nor of the more physical aspects of its properties. For more detailed information on the silicon reagents mentioned, the reader is recommended to consult the books by Fieser and Fieser,Z5O in addition to the primary references. The author gratefully acknowledges many stimulating and helpful discussions with Dr. B. J. Hamill. Most of all, however, sincere tribute must be paid to Professor Gilbert Stork, whose inspiration and talents have contributed so much to the current explosive growth in this area.250 M. Fieser and L. F. Fieser, ‘Reagents for Organic Synthesis’, Vols. 1-5, Wiley-Interscience, New York, 1967-1975.