11 Aliphatic Compounds By R. S. ATKINSON Department of Chemistry The University Leicester LEl 7RH and E. W. COLVIN Department of Chemistry University of Glasgow Glasgow GI 2 8QQ 1 Acetylenes Recent reviews on areas of acetylenic chemistry include synthetic routes to average ring size cycloalkynes,' a theoretical investigation of bonding in metal- acetylene complexes,2 transition-metal complexes of a~etylene,~ intramolecular cyclization reactions with acetylenic bond parti~ipation,~ oligomerization of acetylenes induced by metals of the nickel triad,5 and a book on preparative acetylenic chemistry.6 Several recent studies have been concerned with thermal rearrangements of acetylenes. cis-Hexa-1,5-diyn-3-ene (l) on gas-phase pyrolysis in a flow system at 300 "C,undergoes a degenerate thermal rearrangement.Thus pyrolysis of the dideuteriated analogue (2) causes scrambling of the deuterium between acetylenic and vinyl positions but with either both vinyl positions or both acetylenic posi- tions labelled only [(2) and (3)]. The results demand that the intermediate or R H / \ \ R H / (1) R = H (3) R = D (2) R = D ' H. Meier Synthesis 1972 235. F. R. Hartley Angew. Chem. Internat. Edn. 1972 11 596. L. D. Pettit and D. S. Barnes Fortschr. Chem. Forsch. 1972 28 85. E. E. Voyakovskaya L. N. Shil'nikova N. V. Koshmina and F. Ya. Perveev Reakts. spos. org. Soedinenii 197 1 97. P. M. Maitlis Pure Appl. Chem. 1972 30 427. L. Brandsma 'Preparative Acetylenic Chemistry' Elsevier New York 1971.367 R. S. Atkinson and E. W. Colvin transition state in this scrambling has C-I C-3 C-4 and C-6 equivalent. This intermediate shows radical-type behaviour hence the 1,4-benzenediyl diradical (4)is assumed for its structure rather than a p-benzyne structure (S).7 Phenyl propargyl ether (6) gives indan-2-one and benzocyclobutene on low- pressure gas-phase pyrolysis (-450 "C). The mechanism of formation of indan-2-one (Scheme 1) is based on the work of Schmidt' and supported by employing -0-m J CH=C=O Scheme I the deuteriated propargyl ether (7) which yielded the appropriately labelled indanone (8).9 Pyrolysis studies on (9)" (lo),and (11)" have also been made. Me + D@O D* = 19 "/ deuterium = lOO%deuterium H D C D I (8) H (7) A & fiC HC HC (9) (10) -R.R. Jones and R. G. Bergman J. Amer. Chem. SOC.,1972,94,660. H. J. Hansen and H. Schrnid Chimia (Switz.) 1970 24 89. W. S. Trahanovsky and P. W. Mullen J. Amer. Chem. Soc. 1972 94 591 1. lo M. B. D'Arnore R. G. Bergman M. Kent and E. Hedaya J.C.S. Chem. Comm. 1972 49. 'I T. J. Henry and R. G. Bergman J. Amer. Chem. SOC.,1972,94 5103. Aliphatic Compounds An unusual o-Claisen rearrangement is observed with the sulphoxide (12)which is converted into the thioalcohol (13) by a 2,3- followed by a 3,3-sigmatropic rearrangement without isolation of the allenyl sulphenate (14).12 CH,R Ill js'" -Q R = p-C1-phenoxy Metal- Acetylene Reactions.-Treatment of thiacycloheptyne (15)' with (PhCN),PdCl in tetrahydrofuran affords the yellow cyclobutadiene complex (16)(80%).A suspension of (16)in chloroform reacts with ethylene-bis(dipheny1- phosphine) under nitrogen to give the stabilized cyclobutadiene (17) as a yellow crystalline oxygen-sensitive solid. A distinction between (17a) and (17b) has yet to be made.14 + (PhCN),PdCI -+ S sx Cyclotrimerization of acetylenes with olefins has been accomplished ; N-methylmaleimide and phenylacetylene gave the 2 1 adduct (18) and also the 2 :2 adduct (19).15 l2 K. C. Majumdar and B. S. Thyagarajan J.C.S. Chem. Comm. 1972 83. l3 J. Haase and A. Krebs Z. Naturforsch. 1972 27 624; A. Krebs and H. Kimling Tetrahedron Letters 1970 76 1. l4 H. Kimling and A.Krebs Angew. Chem. Internat. Edn. 1972,11 932. Is A. J. Chalk J. Amer. Chem. SOC.,1972 94 5928. 370 R.S. Atkinson and E. W. Colvin Ph-C-CH ‘ + Ni(COl,(PPh,) ’ Ph &NMe 4-MezaNMe 0 000 0 0 (18) (19) I Me Diethylalkyriylalanes react with a range of simple conjugated enones to give fair to good yields of y6-acetylenic ketones e.g. (20) not accessible by Michael addition of acetylenic anions. The organoalane (21) is easily obtained by converting the terminal acetylene into its lithium salt and then treating with diethylaluminium chloride. A plausible pathway for the reaction involves the intramolecular delivery of the alkynyl group through prior complexation with the carbonyl oxygen as in (22).16 PhC-CLi + Et,AICI --* Et,AIC=CPh + LiCl (21) I R (22) Cycloaddition Reactions.-The 1,3-dipolar addition of mesoionic systems to dimethyl acetylenedicarboxylate (DMAD) is typified by synthesis of pyrroles from A2-oxazolium-5-olates (munchnones) (23) -P (24).’ This reaction has been Me Me I Me0,C phQph C0,Me (24) ’’ J.Hooz and R. B. Layton J. Amer. Chem. SOC.,1971,93 7320. ” R. Huisgen H. Gotthardt H. 0. Bayer and F. C. Shaefer Chem. Ber. 1970,103,2611. Aliphatic Compounds 37 1 \o7-;OzH ii,I (McCOI,ODMAD ’ C0,MeQTlC0,Me H H Me (25) ti,DMAD M I. (MeCOI,O ’ OT H G \I e 0-q~~ N CO,H (26) Me02C C0,Me extended to elaborate fused and functionalized pyrrole rings on to the piperidine rings of (25)and (26) in moderate yields.’ 2-N-Methylaminopyridine adds to carbon suboxide giving (27) which under- goes a 1,4-dipolar addition with DMAD yielding the quinolizone (28) after extrusion of methyl isocyanate.’ Similarly pyridones (29) are obtained from NN’-disubstituted amidines (30).20 Me Me Me I 0 +I I /C/ /C \N + p30-p7 \N 0 0 (27) @COzMe C0,Me @COzMe C0,Me \N \ No 0 0 (28) R2 C0,Me RZ \ DMAD C=NR~ + c,02-+ I -MeNCO -Meo2cOo NHPh 0 R2 I (30) Rl (29) F.M. Hershenson J. Org. Chem. 1972 37 3 1 1 1. l9 K. T. Potts and M. Sorm J. Org. Chem. 1971,36 8. 2o K. T. Pottsand M. Sorm J. Org. Chern. 1972,37 1422. 372 R. S. Atkinson and E. W. Colvin Reaction of the naphthotriazine (31) with DMAD may be construed as a 1,11-dipolar cycloaddition giving the acenaphthotriazine (32) after spontaneous dehydrogenation.2 Me Me (31) Me0,C CO,Me (32) Among additions of DMAD to dienes is its reaction with the arsabenzene (33) to yield arsabarralenes (34).It appears that their reactivity as dienes increases in the order N < P < As in these Group V heterobenzenes.22 C0,Me (33) Ph (34) The first non-condensed thiepin (35) has been obtained by reaction of the pyrrolidinylthiophen (36) with DMAD. An intermediate (36) is detected by n.m.r. monitoring of the reaction mixture where (35) also decays by sulphur ___) MbNA nMAD (37) \ N Me&CO,Me '' C. W. Rees R. W. Stephenson and R. C. Storr J.C.S. Chem. Comm. 1972 1281. 22 G. Markl J. Advena and H.Hauptmann Terrahedron Letters 1972 3961. Aliphatic Compounds extrusion to the benzene derivative (38). The potentially antiaromatic thiepin is stabilized by electron-withdrawing groups.23 Miscellaneous Reactions.-Several papers show that silylation is a useful protective method in synthesis of poly-ynes. Thus the triethylsilyl-protected bromoalkyne (39) can be used successfully in Cadiot-Chodkiewicz coupling of acetylenes (40)+(41); addition of alkali liberates the diyne quantitatively. CU’ NaOH ArCrCH + BrC-CSiEt EtNH,I Ar(CrC),SiEt +Ar(C-C),H DMF-(40) (39) (41) The triethylgermanium compounds behave similarly with the added bonus that the germanium-acetylene bond may also be cleaved by acids without con- comitant hydration of the triple bond (unlike the silicon analogue) a factor which could be useful in synthesis of alkali-sensitive polyene~.~~ Triethylsilyl-protected terminal alkynes can be coupled oxidatively the coupled products partially desilylated (monitoring by u.v.) and then recoupled and completely desilylated (42)-(43).25 The reagents Et,Si(CcC),H (m= 1 2 or 4) may be used in H(C EC)8H +-Et ,Si(C =C),Si Et (43) excess as one component in mixed oxidative couplings allowing extension of terminal poly-yne chains by up to four yne units in a single step.Again the tri- ethylsilyl group is easily removable using base.26 Mechanisms of nucleophilic displacement at acetylenic carbon RCECX + NUC-+ RC-C-NUC + X have been discussed with particular reference to the reactions of phosphines and amines with halogenoacetylenes.Nucleophilic attack using amines occurs on the acetylenic carbon but with phosphines attack on halogen also compete^.^' 2 Alkanes Electrophilic substitutions at alkanes and in alkyl-carbonium ions have been reviewed.28 The barriers to rotation and rotamer preferences in various acyclic alkanes have been determined.29 Effects of halogenoalkanes as solvents on the 3Cn.m.r. spectra of n-alkanes have been studied.30 ” D. N. Reinhoudt and C. G. Kouwenhoven J.C.S. Chem. Comm. 1972 1232 1233. 24 R. Eastmond and D. R. M. Walton Tetrahedron 1972 28,4591. 25 R. Eastmond T. R. Johnson and D. R. M. Walton Tetrahedron 1972 28 4601. 26 T. R. Johnson and D. R. M. Walton Tetrahedron 1972 28 5221. 27 J.I. Dickstein and S. I. Miller J. Org. Chem. 1972 37 2168 2175. ** D. M. Brouwer and H. Hogeveen Progr. Phys. Org. Chem. 1972,9 179. 29 C. H. Bushweller and W. G. Anderson Tetrahedron Letters 1972 181 1. 30 G. Bergmann and J. Dahm Angew. Chem. Internat. Edn. 1972 11 1032. 374 R.S. Atkinson and E. W. Colvin 3 Allenes Syntheses of the allene functional group have been included in a recent v~lume.~ Acetylene- and allene-containing animal alkaloids have been reviewed.32 Cycloaddition of partially resolved cyclonona-1,2-diene and dimethylketen gives an optically active product (44) which is converted into (45) on hydrogena- tion and treatment with base conditions not affecting the chirality of C*. From the absolute configuration of (45) (by 0.r.d.) and knowing the absolute configura- tion of starting cyclononadiene it can be deduced that addition takes place at least preferentially with the keten acting antarafacially and the allene supra- facially (Woodward-Hoffman-allowed .2 + .2J assuming that the two reaction components approach in the least sterically demanding way.33 The case of dimethylketen addition to optically active 1,3-dimethylallene has also been examined and the possibility of suprafacial addition of the keten and antara- facial addition of allene is suggested as a competing (minor) reaction.34 Cyclo- nona-l,2-diene (partially resolved) also reacts with t-butylcyanoketen giving optically active products.The major product (46) has a cis relationship between the t-butyl group and the adjacent CH, which again suggests a synchronous reaction via a .2 (allene) and .2 (keten) addition as shown in (47).35 Y C t C I1 u 0 NC-Secondary deuterium isotope effects support a multistep pathway for all allene [2 + 21 cycloadditions (including dimerizations) but concerted mechanisms for [2 + 31 and [2 + 41 cycl~additions.~~ Support for Dolbier and Dai’s interpreta- tion of secondary deuterium isotope effects has come from study of a reaction known to be a [2 + 21 cycloaddition proceeding via a biradical.Thus when 31 ‘Organic Functional Group Preparations’ ed. S. R. Sandler and W. Karo Academic Press New York 1971 Vol. 2. 32 B. Witkop Experientia 1971 27 1121. 33 M. Bertrand J.-L. Gras and J. Gore Terrahedron Letters 1972 1189.34 M. Bertrand J.-L. Gras and J. Gore Tetrahedron Letters 1972 2499. 35 W. Weyler L. R. Byrd M. C. Caserio and H. W. Moore J. Amer. Chem. SOC.,1972 94 1027. 36 S.-H. Dai and W. R. Dolbier J. Amer. Chem. SOC., 1972 94 3946. Aliphatic Compounds 375 cyclohexa- 1,2-diene is generated from dibromonorcarane (48)it rapidly dimerizes to an intermediate diallylene (49)which can either cyclize to diene (50)or dimerize to two C24H32 stereoisomers. (48) R = H (51) R = D (49) Labelled dibromide (51) was converted into diene [2H2]-(50)whose deuterium distribution was assayed using 2H n.m.r. The spectra obtained correspond to deuterium on vinyl or tertiary positions with a small excess of deuterium on the vinyl position.The magnitude and direction of the isotope effect (kH:k = 1.04) is comparable with that observed by Dolbier and Dai (k,:k = 1.06).37 Thermal cycloaddition of many substituted allenes yielding 1,2-dimethylene- cyclobutanes is believed in many cases to proceed via the intermediate bisallyl biradical(52). The preference for formation of those stereoisomers having larger groups (R) on the ‘inside’ positions of the double bonds of the product (53) can be explained on this model by assuming that they occupy the least-hindered inward positions in (52). Dimerization of diadamantylallene was studied since models suggested a product such as (53 ;R = adamantyl) would be impossible to R H I 2RHC=C=CHR RH C/R RHaC‘R I RH H (53) form. Dimerization was unsuccessful but heating a 3 ”/ solution in di-isopropyl- benzene gave (54) in 60 ”/ yield.This constitutes added evidence for the two-step biradical mechanism for allene dimerization -the biradical in this case being too sterically hindered to undergo ring-closure but instead abstracting hydrogen atoms from di-is~propylbenzene.~~ RCH=C-C=CHR 11 RH,C CH,R (54) R = adamantyl ” W. R. Moore P D. Mogolesko and D. D. Traficante J. Amer. Chem. SOC.,1972,94 4753. 38 T. L. Jacobs and R. C. Kamrnerer J. Amer. Chem. SOC.,1972,94 7190. 376 R. S. Atkinson and E. W.Colvin flCH2 flcCHI CH\\ C\ + ,RlR Rg!R R CH2 (57) R = C0,Me Bisallenyl(55) and DMAD (56)react together to give [2,2]paracyclophane (57) in 32 % yield. Thus [2 + 41 addition to the diene system is followed by dimeriza- tion of the p-quinodimethane (58).Pure biallenyl is unnecessary for the reaction and the crude C,H hydrocarbon mixture from dimerization of propargyl bromide containing -40 % of (55)can be used directly.39 A sector rule for chiral allenes has been derived relating the position of the substituent to the sign of the lowest energy Cotton effect and a physical basis proposed for the Lowe-Brewster rule which relates the configuration of a chiral allene to the sign of its D-line r~tation.~’ 4 Olefins Recent reviews involving olefin chemistry include olefin reactions catalysed by transition-metal compounds ;41 transition-metal complexes of olefins and acety- lenes ;42 transition-metal-catalysed homogeneous olefin disproportisnation ;43 rhodium(1)-catalysed isomerization of linear butenes ;44 catalytic olefin dispro- portionation;45 oxidation of olefins with mercuric salts;46 the syn and anti steric course in bimolecular olefin-forming eliminations ;47 isotope-effect studies of elimination reactions ;48 stereochemistry of Hofmann eliminations ;49 diene synthesis by boronate fragmentation,” Friedel-Crafts acylation of alkenes ;’ olefin oxidation and related reactions with Group VIII noble metal com-pounds ;52 lead tetra-acetate oxidation of ole fin^,^^ epoxidation of olefins by hydroperoxides ;54 mechanism of addition of singlet oxygen to olefins :55 theory 39 H.Hopf Angew. Chem. Internar. Edn. 1972 11 419. 40 P. Crabbe E. Velarde H. W. Anderson S.D. Clark W. R. Moore A. F. Drake and S. F. Mason Chem. Comm. 1971 1261. 41 C. W. Bird Topics Lipid Chem. 1971 2 247. 42 L. D. Pettit and D. S. Barnes Forrschr. Chem. Forsch. 1972 28 85. 43 W. B. Hughes Organometallic Chem. Syn. 1972 1 341. 44 R. Cramer Ann. New York Acad. Sci. 1971 172 507. 45 R. L. Banks Fortschr. Chem. Forsch. 1972 28 39. 46 H. Arzoumanian and J. Metzger Synthesis 1971 527. 47 J. Sicher Angew. Chem. Internat. Edn. 1972 11 200. 48 A. Fry Chem. Soc. Rer. 1972 1. 163. 49 J. L. Coke Selectice Org. Transform. 1972,2 269. 50 J. A. Marshall Synthesis 1971 229. ’’ J. K. Groves Chem. Soc. Reti. 1972 I 73. ” R. Jira and W. Freiesleben Organometallic Reactions 1972 3 1. 53 R. M. Moriarty Selective Org. Transform. 1972,2 183.54 R. Hiatt in ‘Oxidation’ ed. R. L. Augustine Dekker New York 1971 Vol. 2. 55 C. S. Foote Pure Appl. Chem. 1971 27 635. Aliphatic Compounds of cycloaddition reactions ;56 reactions of electron-rich olefins with proton active compounds ;' and the stereochemical features of vinylic radicals.'* Metal-Olefin Reactions.-Few asymmetric syntheses proceeding under catalytic conditions have been reported and high optical purity has been observed only in hydrogenation using optically active catalysts in which the chiral centres are formed as a result of C-H bond formation. A catalyst and con- ditions have been developed which allow the conversion of cyclo-octa-1,3-diene and ethylene into 3-vinylcyclo-octene (59) having an optical purity of 70 %.The chiral catalyst was prepared using an optically active phosphine having chiral R groups.59 Although the transfer of oxygen from a transition metal to an organic sub- strate is well known the reverse is less common. Lower-valent tungsten halides prepared by addition of lithium alkyls to tungsten hexachloride can (a)transform dialkoxides into olefins,6' (b)bring about reductive coupling of aldehydes and ketones to olefins and (c) cause stereoselective reduction of epoxides to olefins in high yield.61 An alternative reagent for stereospecific conversion of epoxides into olefins with retention of configuration is sodium (cyclopentadieny1)dicarbonylferrate(see p. 332).62 A possible pathway in selenium dioxide oxidation of olefins e.g. (60),involves an allylseleninic acid (61).63 Ally1 selenoxides have now been shown64 to undergo ready 2,3-sigmatropic rearrangement to give the selenium(I1) ester ; the isolated R R R H,O ,5 -0 HOSeO CH,OH (60) R = n-butyl (61) 56 W.C. Hernden Chem. Rev. 1972 72 157. 57 J. Hocker and R. Merten Angew. Chem. Internat. Edn. 1972 11 964. L. A. Singer Selective Org. Transform. 1972,2 239. 59 B. Bogdanovic B. Henc B. Meister H. Pauling and G. Wilke Angew. Chem. Internat. Edn. 1972 11 1023. 6o K. B. Sharpless and T. C. Flood J.C.S. Chem. Comm. 1972 370. 61 K. B. Sharpless M. A. Umbreit M. T. Nieh and T. C. Flood J. Amer. Chem. SOC. 1972,94,6538. " W. P. Giering M. Rosenblum and J. Tancrede J. Amer. Chem. SOC.,1972 94 7170. 63 K. B. Wiberg and S.D. Nielsen J. Org. Chem. 1964 29 3353. 64 K. B. Sharpless and R. F. Lauer J. Amer. Chem. SOC.,1972,94 7154. R. S.Atkinson and E. W. Colvin ph\gek I PhSe -v 0-(62) products are derived by hydrolysis of the latter. Thus oxidation of (62) with hydrogen perioxide gives the E-alcohol(63) as the major product. Significantly it is this E-alcohol which is the major product in selenium dioxide oxidation of (60),65 suggesting that the corresponding seleninic acid (61) may undergo a similar rearrangement. A possible mechanism for oIefin disproportionation is the simultaneous rup- ture of both Q-and n-bonds of the chemisorbed olefins by the metal followed by recombination.66 This avoids the postulate of a cyclobutane intermediate,67 for which there is little evidence but suggests that the reaction at some stage has the character of a tetracarbene-metal complex.It has been found6* that a com- mercial cobalt molybdate catalyst shows a similar activity in propene dispropor- tionation as in ethylene formation from diazomethane implying that the sites responsible for both reactions are the same. Oxymercuration-demercuration of olefins is a useful route to alcohols and ethers with Markovnikoff orientation in the addition.69 The relative reactivities of a number of olefins have been determined in order to assess the possibility of selectiveoxymercuration-demercuration of one olefin in the presence of another. The reactivities can be rationalized in terms of carbonium ion stability strain in the double bond and steric interaction^.^' Intramolecular aminomercuration [(64)-+ (65)]has been studied as a function ofvarious parameters including length of chain and effects of substituents on the nitrogen in the chain and on the double bond.” In the case of olefin (66) the n.m.r.spectrum of the intermediate mer- curial shows it to be exclusively one of the two possible diastereoisomers (67). h5 G. Biichi and H. Wiiest Helv. Chim. Acta 1967 50 2440. “ G. S. Levandos and R. Petit Tetrahedron Letters 1971 789. h7 C. P. Bradshaw E. J. Howman and L. Turner J. Curulysis 1967,7,269;F. D. Mango Ah. Catalysis 1969 19 291. 68 P. P. O’Neill and J. J. Rooney J.C.S. Chem. Comm. 1972 104. ‘9 H. C. Brown and P. J. Geoghegan J. Org. Chem. 1970 35 1844; H.C. Brown and M.-H. Rei J. Amer. Chem. Sac. 1969 91 5646. ’O H. C. Brown and P. J. Geoghegan J. Org. Chem. 1972 37 1937 1941. ” J. J. Perie J. P. Laval J. Roussel and A. Lattes Tetrahedron 1972 28 675. Aliphatic Compounds 379 Although a complexing of mercury by nitrogen could be envisaged leading to cis-addition in fact the reaction proceeds by a formal tuans-addition of mercury and nitrogen across the double bond as is shown by detailed examination of the n.m.r. spectra of products from cis-and trans-substituted amino-olefins. Reduc- of (67) with sodium borohydride yields a mixture of (68) and (69) for which an intermediate aziridinium ion is held to be responsible. (67) NaRH4+ The ally1 Grignard reagent (70) cyclizes on heating via a Cope-like transition state (71).The product after hydrolysis was predominantly the cis-cyclopentyl- olefin (72) also obtained in the Cope rearrangement of the corresponding diene.73 A non-cyclic mechanism (73) is known to operate in intermolecular addition where intramolecular electrophilic assistance is available in the ~lefin.~~ CYH2 CC"; ., 'MgBr .-'MgBr I' 70) (71) Cycloaddition Reactions.-Although a common photochemical reaction the thermal cycloaddition of olefins to cyclobutanes is rare in hydrocarbons. Pyrolysis of 1,8-divinylnaphthalene (74) at 425 "C or in solution above 180 "C 72 J. Roussel J. J. Perie J. P. Laval and A. Lattes Tetrahedron 1972 28 701. 73 H. Felkin J. D. Umpleby E. Hagaman and E. Wenkert Tetrahedron Letters 1972 2285.74 H. Felkin and C. Kaeseberg Tetrahedron Letters 1970 4587. R.S. Atkinson and E. W.Colvin gave (75) and (76) in quantitative yield. The driving force for this conversion is the strain caused by enforced close proximity of the n-clouds of the peri-vinyl substituents. A study of the reactions of (77) and (78) suggests that the reaction is a radical one.75 (74) R = H (75) (76) (77) R = D (78) R = Ph A combination of [4+ 21 cycloaddition and 2,3-sigmatropic rearrangement has been used with effect in the synthesis of hasubanan derivatives. Thus the 1-butadienyl phenyl sulphoxide (79) reacts with enamine (80) to yield (81) as a mixture of diastereoisomeric sulphoxides. Heating (81) in the presence of a thiophilic species drives the equilibrium over to the sulphenate (2,3-sigmatropic shift) as the latter is converted into amino-alcohol (82).This annelation sequence may also be used with electron-deficient dienophiles (maleic anhydride methyl vinyl ketone) by employing 1-butadienyl phenyl sulphide (83).76 The only [2 + 2,] concerted cycloadditions of alkenes observed are those involving antarafacial components such as ketens or allenes in which one of the carbon atoms involved has no protruding substituents to hinder close approach of the alkene. To assess whether such a [2 + 2,] reaction is feasible using two 75 S. F. Nelson and J. P. Gillespie J. Amer. Chem. Sac. 1972 94 6237; J. Meinwald and J. A. Kapecki ibid. p. 6235. '6 D. A. Evans C. A. Bryan and C. L. Sims J. Amer.Chem. Sac. 1972,94 2891. Aliphatic Compounds 381 alkenes the separate reactions of cis-and trans-dideuterioethylene with tri- fluoroethylene were studied. The i.r. spectra of the reaction products from both isomers were identical and significantly different from that of authentic (84). This result is that expected from a stepwise cyclsaddition involving biradical intermediates with high loss of c~nfiguration.~~ Oxyallyl cations can be generated from e.g. 2-dimethylamino-4-methylene-1,3-dioxolans (85)7* or from ad-dibromoketones on debromination in situ with zinc in glyme. In the presence of traces of acids (85) liberates dimethylamine to generate the dioxolenium ion (86) which opens to the W-shaped allylic cation (87) stereospecifically.Addition of the latter to cyclopentadiene or furan takes place preferentially by a boat transition state (88) to give bicyclic ketones (89).79 Z = 0 or CH, R = CHO This is in contrast to the simple 2-methylallyl cation which adds preferentially via a chair transition state.*' The synthesis of 2-methoxyallyl halides (90) has been reported by two independent routes the reaction of 2-methoxypropene P. D. Bartlett G. M. Cohen S. P. Elliot K. Hummel R. A. Minns C. M. Sharts and J. Y. Fukunaga J. Amer. Chem. Sac. 1972,94,2899. H. M. R. Hoffmann K. E. Clemens E. A. Schmidt and R. H. Smithers J. Amer. Chem. Sac. 1972,94 3201. H. M. R. Hoffmann K. E. Clemens and R. H. Smithers J. Amer. Chem. SOC.,1972 94 3940. H. M. R. Hoffmann and D. R. Joy J. Chem.SOC. (B) 1968 1182. 382 R.S. Atkinson and E. W. Colvin with N-halogeno-succinimides and the pyrolysis of l-halogeno-2,2-dimethoxy-propane.8 These halogenomethoxypropenes also provide precursors for 2-methoxyallyl cations on treatment with silver trifluoroacetate.82 CH,X (90) X =C1 or Br Addition of a mixture of isomeric nitronic esters (91) and (92) to cis-olefins yields endo-adducts. With dimethyl fumarate isoxazolidines (93) and (94) are obtained.83 These isoxazolidines both consist of single invertomers at nitrogen,84 and the cycloaddition apparently proceeds under kinetic control since boiling in toluene yields the thermodynamically more stable isomers in excess by inversion at nitrogen. Hence in the cycloaddition rehybridization of the nitrogen lone pair takes place specifically on to one side of the plane of the original dipole.85 -0 0-‘\ /H N=C N=C /+ \H /+ \ Me0 Me0 C0,Me Me0,C H H-tf -CO Me N C0,Me MeO-N /o .‘C-C0,Me MeO-N /o OMe H’ HxC02Me . (931 Me0,C H r(/ Me02C H-$02Me C0,Me O\N ‘tH OMe (94) G. Greenwood and H. M. R. Hoffmann J. Org. Chem. 1972,37 61 1. 82 H. M. R. Hoffmann Angew. Chem. Internat. Edn. 1972 11 324. ” R. Gree and R. Carrie Tetrahedron Letters 1971 41 17. 84 K. Muller and A. Eschenmoser Helv. Chim. Acta 1969,52 1823;G. V. Lagodzinskaya Zhur. strukt. Khim. 1970 11 1. 85 R. Gree and R. Carrie Tetrahedron Letters 1972 2987. Aliphatic Compounds 1,3-Dipolar reagents and the classical Diels-Alder addition of dienes both usually require activated olefins and few enophiles are known which cycloadd readily to isolated double bonds.Such an enophile is the N-alkyl-N-vinyl- nitrosium ion (95) generated in situ by silver(1)-induced ionization of a-chloro-nitrones (96). Cycloaddition takes place in the presence of olefins to give (97).8b-88 Further ramifications of this method are discussed on p. 363. (96) (97) Other Reactions of 0lefins.-In spite of its popularity in undergraduate textbooks the oxidation of olefins to cis-l,2-glycols by alkaline potassium permanganate is a poor reaction giving with a few exceptions low yields. A modification uses phase-transfer catalysts (benzyltriethylammonium chloride- methylene dichloride-aqueous base) to yield 1,2-glycols in 50 % yield.' Potassium permanganate is solubilized in benzene by adding crown polyethers to form reagents which are also useful oxidants for olefins.Internal olefins are converted into carboxylic acids (if disubstituted) or ketone-acids (if trisubsti-tuted." The stereochemistry of solvolytic displacement at unsaturated (vinyl sp2) carbon has been studied using trifluoromethanesulphonates (triflates) as leaving groups. Solvolysis of Z-and E-triflates (98) and (99) in trifluoroethanol gave rise to different ratios of products (100) and (101); a greater proportion of (101) is formed from (99) than from (98). The results are best accommodated by assuming the intervention of ion pairs in which the departing triflate group shields the molecule from attack by solvent." uic-Dialkylidenecycloalkanes (102) are chiral although attempts at resolu- tion have been unsuccessful.92 The rate of racemization of (103) prepared by isomerization of (104) has been measured using n.m.r.and the coalescence of the diastereotopic methylene protons. Close approach of the inside methyl groups is entirely responsible for the activation energy of the process (88 kJ mol-') 86 U. M. Kempe T. K. Das Gupta K. Blatt P. Gygax and A. Eschenmoser Helu. Chim. Acra 1972 55 2 187. '' T. K. Das Gupta D. Felix U. M. Kempe and A. Eschenmoser Helu. Chim. Acfa 1972,55 2198. P. Gygax T. K. Das Gupta and A. Eschenmoser Helv. Chim. Acta 1972 55 2205. 89 W. P. Weber and J. P. Shepherd Tetrahedron Letters 1972 4907. 90 D. J. Sam and H.E. Simmons J. Amer. Chem. SOC.,1972,94 4024. 91 T. C. Clarke D. R. Kelsey and R. G. Bergman J. Amer. Chern. Soc. 1972 94 3626; T. C. Clarke and R. G. Bergman ibid. p. 3627; R. H. Summerville and P. von R. Schleyer ibid. p. 3629. 92 K. B. Alberman R. N. Haszeldine and F. B. Kipping J. Chern. SOC.,1952 3287; F. 9.Kipping and J. J. Wren ibid. 1957 3246. R.S. Atkinson and E. W. Colvin -0Tf Bu Bu Bu \ /OTf \ + \ /Me c=c --+ C=C-Me + c=c / /\ Me./\Me Me Me OCH,CF 1 Bu / \+ (loo) Me/C=C-Me t \ Bu \ /Me Bu \ Bu ,OCH,CF + Me./c=c\ OTf + Me / C=C-Me + Me/c=c\ Me -OTf (99) Me (103) and as expected the barrier is significantly higher than that (<50 kJ mol- ’) of (105).93 5 Carboxylic Acids Data presented94 for the product composition in the pyrolysis of calcium decanoate allow the prediction of the complete set of pyrolytic products for a given saturated monoacid salt ;unsaturated acid and diacid salts give much more diverse and numerous products.The mechanism of dehalogenative decarboxyla- tion of P-bromoacids has been subjected to kinetic ~crutiny,~’ which confirmed its assignment to the general class of heterolytic fragmentations. 93 G. F. Kiefer J. J. Levek and T. T. Bopp J. Amer. Chem. SOC.,1972 94,4751. 94 R. A. Hites and K. Biemann J. Amer. Chem. SOC.,1972,94 5772. 95 W. R.Vaughan W. F. Cartwright and B. Henzi J. Amer. Chem. SOC.,1972,94,4978. Aliphatic Compounds A polystyrene resin containing the chiral complex of copper(i1) with N-methoxycarbonyl-L-valine effects the partial resolution96 of a-aminoacids ; the L-acid co-ordinates preferentially.Equilibrium constants have been deter- mined in a number of solvents for the ring-chain tautomerism of substituted cis-3-benzoyL9 and cis-3-acyl-acrylic acids.98 The anion of methyl hydrogen di-isopropylmaleate is rapidly hydrolysed by an unassisted nucleophilic dis- placement of methoxide ion by the carboxyl ion ;this phenomenon is ascribed99 to the effect of strain in the system increasing the concentration of the tetrahedral intermediate (106) sufficiently to make the relatively unfavourable loss of methoxide significant. Pr' (106) The formation of fl-lactones as kinetic products in the halogeno-lactonization of py-unsaturated carboxylic acids is now considered'00 to be quite general.The absolute configurations of (-)-carlosic acid"' and (+)-tropic acidlo2 have been shown to be (S) and (R),respectively. 6 Carboxylic Acid Esters The hitherto elusive a-lactones have been synthesized photochemically by irra- diation of substituted malonyl peroxides at 77 K in an i.r. ce11;'03 the a-lactone produced shows carbonyl absorption at 1895 cm-and C-0 absorption at 1163 cm-;secondary photoproducts are as shown in Scheme 2. Treatment of malonyl peroxide with triphenylphosphine lo4 generates malonyl anhydrides and the corresponding ketens by two different decomposition modes of the intermediate (107) (Scheme 2). In a definitive series of papers,'" the marked acceleration by certain additives such as dimethylformamide or 1,2-dimethoxyethane on the rate of alkylation of the sodium enolate of diethyl n-alkylmalonates in benzene solution has been studied with a view to identifying the reactive species; the evidence obtained 96 R.V. Snyder R. J. Angelici and R. B. Meck J. Amer. Chem. SOC.,1972,94 2660. '' K. Bowden and M. P. Henry J.C.S. Perkin II 1972 201. 98 K. Bowden and M. P. Henry J.C.S. Perkin II 1972 206. 99 M. F. Aldersley A. J. Kirby and P. W. Lancaster J.C.S. Chem. Comm. 1972 834. loo W. E. Barnett and W. H. Sohn J.C.S. Chem. Comm. 1972,472; Tetrahedron Letters 1972 1777. J. L. Bloomer and F. E. Kappler J.C.S. Chem. Comm. 1972 1047. M. B. Watson and G. W. Youngson J.C.S. Perkin I 1972 1597. lo' 0. L. Chapman P.W. Wojtkowski W. Adam 0.Rodriquez and R. Rucktaschel J. Amer. Chem. SOC.,1972 94 1365. W. Adam and J. W. Diehl J.C.S. Chem. Comm. 1972 797. G. H. Barlow and H. E. Zaugg J. Org. Chem. 1972 37 2246; H. E. Zaugg J. F. Ratajczyk J. E. Leonard and A. D. Schaefer ibid. 2249; H. E. Zaugg and J. E. Leonard ibid. 2253. R. S. Atkinson and E. W. Colvin 0 hv 77"KI CO + -P CO + R,CO R 0 1 Ph,P v (1 07) Scheme 2 suggests either a solvent-separated ion pair or a contact ion pair with a larger interionic distance than that in the solvated ion pair and which is in equilibrium with the micellar system In a kinetic and mechanistic investigationlo6 of the isomerization of allylic esters in acetic acid catalysed by palladium(1r) chloride it has been found that two pathways are operative one involving simultaneous exchange and isomeriza- tion the other isomerization without exchange (Scheme 3).In the latter pathway labelling shows the involvement of a 1,3-acyloxonium ion. MeCH=CHCH,OCOEt S MeCH=CHCH,OAc OAc OCOEt I I CH,=CHCHMe -CH,=CHCHMe Scheme 3 The products observed in the pyrolysis of lactone toluene-p-sulphonyl- hydrazone sodium salts can be accounted for by formation of an intermediate oxycarbene.lo' Controversy'08 continues over the precise nature of the transition state in the p-cis thermolytic ester elimination reaction. Whereas one group"' interpret lob P. M. Henry J. Amer. Chem. Sac. 1972 94 1527 5200. lo' A. M. Foster and W. C. Agosta J. Amer. Chem.SOC.,1972 94 5777. log A. Tinkelenberg E. C. Kooyman and R. C. Louw Rec. Trav. chim. 1972,91 3. lo9 H. Kwart and J. Slutsky J.C.S. Chem. Comm. 1972 1182. A liphatic Compounds 387 their data as indicative of a symmetrical non-heterolytic non-planar transition state (108),analogous to other pericyclic fragmentations another author '* proposes charge development (log) defining the order of extent of movement of electrons as 1 > 2 > 3. I C HH Ar" The effect of structure on the rate of gas-phase pyrolysis of acetates and car- bonates*''has been found to be similar the faster rate of the latter being derived equally from lower activation energies and more positive entropies of activation. The ct-elimination of acetic acid from methyl acetate derivatives has been observed' '*in gas-phase pyrolysis ; a five-membered cyclic transition state is proposed the other products being interpretable on the basis of unirnolecular fragmentation and/or isomerization of the co-produced carbene (Scheme 4).lX ox H.. . . . . C X II I i'Y MeC-0-CH 0. 0 + MeC0,H + :C-Y 1 Y -C+ I Me X = H Y = OMe OPh SMe X = OMe OEt Y = OMe OEt Scheme 4 With the analogous S-methoxymethyl thioacetates a novel p-elimination reaction occurs' (Scheme 5). When 2-chloro-1-methoxyethyl acetate or thioacetate is 0 II MeC-SCH,OMe --+ MeC0,Me + CH,=S + MeCOSMe Scheme 5 pyrolysed in the gas phase hydrogen chloride elimination with rearrangement is observed114 (Scheme 6). ' R. Taylor J.C.S.Perkin 11 1972 165. D. B. Bigley and C. M.Wren J.C.S. Perkin ZI 1972 926 1744. P. C. Oele and R. Louw Tetrahedron Letters 1972,3623 (printed correctly on p. 4941). P. C. Oele and R. Louw J.C.S. Chem. Comm. 1972 848. P. C. Oele R. Louw and A. Tinkelenberg Tetrahedron Letters 1972 5159. R. S. Atkinson and E. W. Colvin ClCH=CHOMe + MeCOSH CICH,CH \ SCOMe MeCOSCH=CHOMe + HCI Scheme 6 The hindered amino-diester (1 10) has been synthesized (Scheme 7) and shows' significant activity in oivo on lympbocytic leukemia; the preferred conformation (110a) is such that its mode of action bridging RNA or DNA strands is probably similar to that of the well-known nitrogen mustard dialkylat- ing agents. 0 (1 IOa) Scheme 7 The hydrolysis of isopropenyl acetate is catalysed by organomercury(1r) and bis(organo)thallium(w) ions ; an oxymetalation-demetalation sequence is pro-posed.'' Whereas the reduction of dimethyl bismethylmalonate with sodium in xylene is reported"' to yield the keten acetal (111) in the presence of trimethylchloro- silane when the solvent is ammonia a mixture of products is formed,' l8 includ-ing the cyclopropanediol di(trimethylsily1)ether (1 12).This diol on treatment with sodium methoxide gives the products shown (Scheme 8) possibly by Cannizzaro disproportionation of the intermediate aldehyde (113). ' P. Y. Johnson and I. Jacobs J.C.S. Chem. Comm. 1972,925. P. Abley J. E. Byrd and J. Halpern J. Amer. Chem. SOC.,1972 94 1985. 'I' Y. N. Kuo F. Chen C.Ainsworth and J. J. Bloomfield Chem. Comm. !971 136. 'I8 F. Chen and C. Ainsworth J. Amer. Chem. SOC. 1972 94 4037. Aliphatic Compounds OMe Me,C(CO,Me) 4Me,C=C' \ OSiMe, (111) \ OSiMe '0-H CH,OH + XCH2OH XCH20H C0,H t-XCH0 CH20H The first case of a C-0 migration of an ethoxycarbonyl group has been observed' l9 (Scheme 9). -+ CHO OH -0 J Scheme 9 According to MO-LCAO-SCF calculations,' 2o the magnitude of the shift of the carbonyl stretching frequency in the i.r. of a-lithio-esters as compared with the non-metalated analogues indicates the degree of ionic character of the C-Li 119 F. W. Lichtenthaler and G. Bambach J. Org. Chem. 1972 37 1621. 12' J. KfiZ and P. Schmidt Tetrahedron 1972 1033. R.S. Atkinson and E. W.Coluin bond; the results obtained support a model of a strongly polarized covalent C-Li bond as opposed to the simple ionic picture. A novel synthesis12' of 0-methyl thioformate has been described. The direct introduction of the acyloxy- group has been reviewed. ' Rubrenolide (1 14) and rubrynolide (I 13 two structurally novel lactones have been isolated' 23 from the Amazonian tree Neactandra rubra. cis-Dec-5-en-l-yl-3-methyl butanoate (116) has been identified as the sex pheromone'24 of the Pine Emperor Moth (Nudaurelia cytherea cytherea Fabr.) a pest indigenous in South African pine plantations. (114) R = CH=CH2 (115) R = C-CH 7 Carboxylic Acid Amides The question of 0-us. N-protonation of amides has recently been raised anew.' Liler,'26 using U.V.spectroscopy has suggested that benzamide is 50 :50 0 :N protonated in 80% sulphuric acid. However a considerable body of evidence has been produced to show that protonation or Lewis acid complexation of amides consistently occurs by co-ordination with oxygen. Studies have included the acidity dependent changesI2' in the n-n* and n-n* bands of aliphatic amides; kinetic evidenceI2' based on rate data for acid-catalysed amide hydrolysis in both dilute and concentrated acid ; an n.m.r. study' 29 of proton-exchange rates where for N-methylacetamide the molar ratio of 0 :N protonated species is greater than lo6; a "N n.m.r. of adducts of boron trifluoride and antimony pentachloride with '5N-labelled ureas where the hybridization- dependent "N-H coupling constants were inconsistent with N-co-ordination ; Iz1 D.H. Holsboer and H. Kloosterziel Rec. Truu. chim. 1972 91 1371. 22 D. J. Rawlinson and G. Sosnovsky Synthesis 1972 1. N. C. Franca 0. R. Gottleib D. T. Coxon and W. D. Ollis J.C.S. Chem. Comm. 1972 514. 124 H. E. Henderson F. L. Warren 0. P. H. Augustyn B. V. Burger 0. F. Schneider P. R. Boshoff H. S. C. Spies and H. Geertsema J.C.S. Chem. Comm. 1972 686. 125 M. Liler J.C.S. Perkin IZ 1972 816. 126 M. Liler J.C.S. Chem. Comm. 1972 527. '' H. Benderly and K. Rosenheck J.C.S. Chem. Comm. 1972 179. C. R. Smith and K. Yates Canud. J. Chem. 1972,50 771. 129 R. B. Martin J.C.S. Chem. Comm. 1972 793. 130 P. Stilbs Tetrahedron Letters 1972 227. Aliphatic Compounds 39 1 i.r.and n.m.r. evidence ;13' catalysis of the imidate-imide rearrangement'32 by Lewis acids and alkyl halides ;and finally the effect of alkali-metal cations on the torsional barrier about the N-C(0) bond in amides,'33 when it was found that lithium ions served to increase this barrier an effect ascribed to complexa- tion with oxygen increasing the importance of (1 17) as a contributing structure complexation with nitrogen would decrease the barrier by preventing delocaliza- tion of the N lone pair of electrons into the N-C(0) bond. R 0-\t / R /N=C\ R Several N-t-butoxyamido radicals' 34 and amido free radicals' 35 themselves have been generated and observed by e.s.r. spectroscopy; a n ground state is unanimously assigned.The paramagnetic species generated and studied by a French group,136 who interpreted them as amido radicals have now been shown to be the corresponding acyl nitroxides.135" A combination of 3C Fourier transform and partially relaxed Fourier trans- form spectroscopy has been utilized' 37 to determine steric compression shifts in aliphatic amides and oximes allowing a sensitive study of internal rotation etc. The synthesis of ON-bis(trimethylsily1)formamidehas been reported,' 38 and some of its reactions have been determined (Scheme 10). OSiMe, /OSiMe3 RCOCH,COR 1 HCONH 1,H-C R-C=CHCOR \\ \-NSiMe + HCONHSiMe, RCH,CN R \ C=CHNH + Me,SiOSiMe, / NC' Reagent i Me,SiCi-Et,N Scheme 10 L. Hendriksen and B. Baltzer Tetrahedron Letters 1972 2485.32 B. C. Challis and A. D. Frenkel J.C.S. Chem. Comm. 1972 303. W. Egan T. E. Bull and S. Forsen J.C.S. Chem. Comm. 1972 1099. 134 T. Koenig J. A. Hoobler and W. R. Mabey J. Amer. Chem. Soc. 1972,94 2514. 135 (a) W. C. Danen and R. W. Gellert J. Amer. Chem. Soc. 1972 94 6853; (6) Y. L. Chow and R. A. Perry Tetrahedron Letters 1972 53 1. 136 P. Tordo E. Flesia and J. M. Surzur Tetrahedron Letters 1972 183; P. Tordo E. Flesia J. M. Surzur and G. Labrot Tetrahedron Letters 1972 1413. '" G. C. Levy and G. L. Nelson J. Amer. Chem. SOC.,1972 94,4897. 13* W. Kantlehner W. Kugel and H. Bredereck Chem. Ber. 1972 105 2264. 392 R.S. Atkinson and E. W. Colvin An unsymmetrical concerted transition state has been assigned to the thermal p-elimination reaction of alkyl NN-dimethylcarbamates ; both and systems lead to the conclusion of a unimolecular reaction involving heterolytic rather than homolytic fission.A new type of basic amide hydrolysis characterized by N-alkyl fission has been rep~rted,'~' and is exemplified in Scheme 11. N=NPh -+ RCON=C(Me) Scheme I1 8 Nitriles A proposed step in the prebiotic polymerization of HCW the dimerization of iminoacetonitrile (118) to the HCN tetramer diaminomaleonitrile (119),has been achieved142 with the N-t-butyl derivative of (118). Di-iminosuccinonitrile (120) an oxidized form of the tetramer has been prepared'43 as shown (Scheme 12); catalytic reduction afforded diaminomaleonitrile. Ti i NC-CN + 2HCN -!+ NcHNH HN CN Reagents i Et,N; ii H2-Pd/C ( 120) Scheme 12 9 Ketones The search for the hypothetical oxyallyl zwitterion (121) and the postulations of its intermediacy continue unabated ;reductive transformations of aa'-dibromo-ketones plausible precursors of the zwitterion have been extensively studied.IJ9 H. Kwart and J. Slutsky J.C.S. Chem. Comm. 1972 552. 14' N. J. Daly and F. Ziolkowski J.C.S. Chem. Comm. 1972 911; CJ refs. 15 16 17 ''I F. H. Stodola J. Org. Chem. 1972 37 178. H. Dabek R. Selvarajan and J. H. Boyer J.C.S. Chem. Comm. 1972 244. 143 0. W. Webster Angew. Chem. Internat. Edn. 1972 11 153. Aliphatic Compounds 393 Reduction of such ketones with a Zn-Cu couple in DMF yields 2-dimethyl- amino-4-methylene-l,3-dioxolans(122) by formal 1,3-dipolar addition of solvent to the hypothetical zwitterion ;144 such species are reported'45 to decompose spontaneously in the presence of suitable dienes to give adducts whose structures suggest the intermediacy of the parent zwitterion.Interest-ingly mild acid-catalysed hydrolysis of the dioxolan (122) affords 2,4-dimethyl- penta-l,3-dien-3-01(123) as a relatively stable aliphatic enol ;146such stability has been rationalized in an ab initio MO of the effects of a-substitution on keto-enol tautomerism when it was found that for all the substituents studied the enol structure was stabilized preferentially to the keto form owing to greater interaction with the double bond. When methanol is used as solvent the reduc- tion of ad-dibromoketanes with a Zn-Cu couple leadsI4* to the parent ketone and the a-methoxyketone :once again the oxyallyl zwitterion is implicated.OH H Me+H Me Me Electrochemical reduction of m'-dibromoketones has been studied' 49 as a potential route to cyclopropanones; no such species was detected and the products obtained were rationalized in terms of an oxyallyl zwitterion or an enol allylic bromide. Later however cyclopropanone hemiacetals were isolated '50 from such reductions in methanol. The oxyallyl zwitterion is involved in a mechanistic s~herne'~' to explain the production of cycloheptenones cyclopentanones and cyclopentenones' 52 by the reaction of ad-dibromoketones with iron carbonyl (Scheme 13). The intermediacy of organoiron halide complexes is proposed 153 to account for the products observed in the reaction of a-halogenoketones with iron pentacarbonyl.has presented a correlation between the conjugate addition of lithium dimethylcopper to ap-unsaturated carbonyl compounds and their L44 H. M. R. Hoffmann K. E. Clemens E. A. Schmidt and R. H. Smithers,J. Amer. Chem. SOC.,1972 94 3201. 145 H. M. R. Hofmann K. E. Clemens and R. H. Smithers J. Amer. Chem. SOC.,1972 94 3940. 146 H. M. R. Hofmann and E. A. Schmidt J. Amer. Chem. Soc. 1972,94 1373. 14' W. J. Hehreand W. A. Lathan J.C.S. Chem. Comm. 1972 771. 14' H. M. R. Hofmann T. A. Nour and R. H. Smithers J.C.S. Chem. Comm. 1972,963. 149 J. P. Dirlam L. Eberson and J. Casanova J. Amer. Chem. Soc. 1972,94,240. I5O A. J. Fry and R. Scoggins Tetrahedron Letters 1972 4079.151 R. Noyori Y. Hayakawa M. Funakura M. Takaya S. Murai R. Kobayashi and S. Tsutsumi J. Amer. Chem. SOC.,1972 94 7202. 152 R. Noyori K. Yokoyama S. Makino and Y. Hayakawa J. Amer. Chem. SOC.,1972 94 1772. H. Alper and E. C. H. Keung J. Amer. Chem. SOC.,1972,94 2566. 54 H. 0.House and M. J. Umen J. Amer. Chem. SOC.,1972,94 5495. 1540H.0.House L. E. Huber and M. J. Umen J. Amer. Chem. SOC.,1972 94 8471. R. S. Atkinson and E. W. Coluin A Br Br r6 R 0 Scheme 13 polarographic reduction potentials. Such a correlation is compatible with the first step of the mechanism (Scheme 14)proposed for this reaction and in conjunc-tion with empirical rules for the estimation (with an accuracy of k0.l V) of the reduction potentials of such unsaturated compounds 54a offers the ability to predict both when conjugate addition will be successful and when reduction of the olefinic linkage will be a serious competitor.A plausible explanation of the preference for 1,2-or 1,4-addition1 55 or reduction' s6 processes of o$-unsaturated carbonyl compounds has been advanced based on Pearson's theory of hard and soft acids and bases the 4-carbon being considered softer than the 2-carbon; rational variation of reagent then permits alteration of this preference. -+ [A]'R-C=C-CHR I 0-Me R-CH-CH=C-R + (MeCu) + 0.5 (LiCuMe,) + 1 I Me 0Li R 0-Scheme 14 The reduction of P-chlorovinyl aldehydes by zinc powder leads to selective removal of the @-chlorine substituent but if the reduction is performed in the 15s 0.Eisenstein J.-M. Lefour C. Minot N. T. Anh and G. Soussan Compt. rend. 1972 274 C 1310. 156 J. Bottin 0.Eisenstein C. Minot and N. T. Anh Tetrahedron Letters 1972 3015. Alip hatic Compounds presence of air reductive coupling is observed'57 (Scheme 15). The mechanism of such one-electron reductive coupling reactions has been subjected to further ~crutiny.'~' R' R' \/ H/C=C\CHO R' --< \/ /c=c\R2 C1 CHO CH =C(R2K;f2 [K Scheme 15 The first example has been reported'" of a normal base-catalysed intermolecu- lar condensation of a diazomethyl ketone with two potential reaction sites (Scheme 16). PhCH2COCHN2 + PhCHO -+ PhCH,COCCH(OH)Ph It N2 Scheme 16 The influence of the structure of the aldehyde on the regioselectivity of base- catalysed mixed ketolization with methyl methylene ketones has been studied.In the base-induced bromination of butan-2-one in aqueous solution each hydro- gen on the 1-carbon and the 3-carbon is attacked equally fast to form an enolate,16' the resulting enolates rapidly giving bromoform and propionate and lactate salts respectively (Scheme 17). Contrary to currently held views the variation in enol content as a function of structure in fl-diketones is due to varia- tion in energy of the ketones and not of the enols; the situation is reversed however in Ij-ketoesters.'h2 The heats of formation of aliphatic ketones have been further studied,'63 and an improved force-field method for the calculation of the structures and energies of carbonyl compounds has been described.Ab initio calculation^'^^ on acetone show that the methyl groups have hydrogen eclipsing oxygen in the ground state and that the rotational barrier is 0.99 kcal mol- '. '" A. Hara and M. Sekiya Chem. and Pharm. Bull. (Japan),1972 20 309. '" S. L. Thuan and J. Wiemann Bull. SOC.chim. France 1972 1861. 159 N. F. Woolsey and M. H. Khalil J. Org. Chem. 1972 37 2405. 16' J.-E. Dubois and P. Fellmann Tetrahedron Letters 1972 5085. 16' C. G. Swain and R. P. Dunlap J. Amer. Chem. SOC.,1972,94 7204 Ih2 P. Alcais and R. Brouillard J.C.S. Perkin 11 1972 1214. 163 J.-E. Dubois and H. Herzog J.C.S. Chem. Comm. 1972 932. 164 N. L. Allinger M. T. Tribble and M. A. Miller Tetrahedron 1972 1173.165 N. L. Allinger and M. J. Hickey Tetrahedron 1972 2157. R.S. Atkinson and E. W. Colvin 0 0 i-CHBr 1 + Scheme 17 The utility of bifunctional reagents such as oxalic acid monohydrazide for the resolution of racemic carbonyl compounds has been reported.'66 A four-centred transition state (124) is proposed'67 for the bimolecular substitution of P-halogenoketones and related compounds (Scheme 18). 0 0 ] II RCCH,CH,X + Y-+ [R-cIyH2 -+ RCCH,CH,Y II YfiXCH --Xb-+ X-Scheme 18 Glyoxal reacts with ethyl carbamate under acid catalysis to give 1,1,2,2-tetra(ethoxycarbony1amino)ethanel6*(125) and not as previously reported glyoxal bis(ethoxycarbony1imide) (126). Gyrinal (127) has been identified'69 as an arthropod defensive substance.0 CH(NHCO,Et) CH=NCO,Et I I CH(NHCO,Et) CH=NCO,Et (125) (126) (127) 10 Amines Even a complete thermodynamic analysis'" of the anomalous order of amine basicities in solution utilizing gas-phase basicities' 71-1 72 and thermodynamic 166 H. Kaehler F. Nerdel G. Engemann and K. Schwerin Annalen 1972 757 15. *" E. N. Trachtenberg and T. J. Whall J. Org. Chem. 1972 37 1494. 16' G. F. Whitfield R. Johnson and D. Swern J. Org. Chem. 1972. 37.95. L69 H. Schildknecht H. Neumaier and B. Tauscher Annalen 1972 756 155. E. M. Arnett F. M. Jones M. Taagepera W. G. Henderson J. L. Beauchamp D. Holtz and R. W. Taft J. Amer. Chem. SOC.,1972 94 4724. D. H. Aue H. M. Webb and M. T. Bowers J. Amer. Chem. SOC.,1972,94,4726.172 J. P. Briggs R. Yamdagni and P. Kebarle J. Amer. Chem. SOC.,1972 94 5128. Aliphatic Compounds dissolution properties has failed to provide an easy interpretation of this phenomenon. Much attention has been paid to aliphatic azoxy-compounds partly due to their potent physiological properties which range from therapeutic antibiotic behaviour to high carcinogenicity. Following a model of isomeric azoxy-compounds and a revision' 74 of absolute stereochemistry the antibiotics elaiomycin (128) and LL-BH 872a (129) have now been both assigned the Z stereochemistry for the azoxy-group. The methyl diazonium cation (130) has been identified'25 as the reactive methylating species of the toxin aglycone Z-methyl-ONN-azoxymethanol (13 1). A previously reported process' 76 has H MH Me(CH,),CH N=N CH,OMe J 'c( 0 I CHOH HH Me(CH,),CH >=(N=N.,COCH,OH Me + \ (131) been generalized' 77 to provide a flexible and directed synthesis of azoxyalkanes (Scheme 19). The Z-E thermal isomerization of aliphatic azodioxy-compounds Et \R2 Reagents i Et,OBF,-CH,CI,; ii R21-HMPA Scheme 19 K. G. Taylor and T. Riehl J. Amer. Chem. SOC.,1972,94,250. W. J. McGahren and M. P. Kunstmann J. Org. Chem. 1972,37 902. M. H. Benn and P. Kazmaier J.C.S. Chem. Comm. 1972 887. "' R. A. Moss and M. J. Langdon Tetrahedron Letters 1969 3897. R. A. Moss M. J. Langdon K. M. Luchter and A. Mamantov J. Amer. Chem. SOC. 1972,94,4392. R. S. Atkinson and E. W. Colvin (dimeric nitrosoalkanes) has been shown to occur exclu~ively'~~ by a dissocia- tion-recombination mechanism.In the reductive rearrangement of t-nitrosoalkanes with trialkyl phosphites the nitrene (132) was invoked' 79as a possible intermediate. Later results indicatedI8' that the phosphate ester (133) decomposed directly in a concerted process to the observed products. R3C-N=0 + (EtO),P --+ P-+R,C-N-bO-P(OEt)3I S R + R,C-N (132) + (EtO),PO (133) (EtO),PO + R,C=NR + R,CO + RNH Scheme 20 It has been shown18' by isotopic labelling that the exchange reaction of nitroso- alkanes with nitric oxide occurs via oxygen-atom transfer and not by a displace-ment mechanism (Scheme 21). Scheme 21 Microwave spectroscopic studies on aminoacetonitrile and some deuteriated analogues indicate'82 that the amino and methylene groups are trans to each other (134).H H H35H The preparation of pure di-imine by high-vacuum pyrolysis of the sulphon- amide salt (135) has been reportedIg3 (Scheme 22); it is a yellow liquid unstable above -150 "C. Th. A. J. W. Wajer and Th. J. De Boer Rec. Trav. chtm. 1972,91 565. B. Sklarz and M. K. Sultan Tetrahedron Letters 1972 1319. R. Abramovitch J. Court and E. P. Kyba Tetrahedron Letters 1972 4059. 181 P. J. Carmichael B. G. Gowenlock and C. A. F. Johnson J.C.S. Perkin 11 1972 1379. I a2 J. N. Macdonald and J. K. Tyler J.C.S. Chem. Comm. 1972 995. lS3 N. Wiberg H. Bachhuber and G. Fischer Angew. Chem. Internat. Edn. 1972,11,829. Aliphatic Compounds 399 \ Tos ,N-N H Tos /' \ -L N-N /H-J!+ HN=NH H \H Na / \H (135) Reagents i NaN(SiMe,),; ii heat Scheme 22 11 Alcohols A general method lS4 for distinguishing threo from erythro diastereoisomers of certain a-glycols and related compounds has been described based on the detection of W long-range coupling or an intramolecular Overhauser effect respectively in the n.m.r.spectra of the corresponding acetonides (Scheme 23). R' RZ 'W' XH -Me YH RZ 'NOE' Scheme 23 Chiral alcohols have significant Cotton effects between 185 and 198 nm. Where the preferred conformation of the hydroxy-group cannot be defined unambiguously Cotton effects are small but for the majority of compounds with clearly preferred conformations the observed sign'85 agrees with the prediction.A new procedure'86 for the identification and analysis of A3- A4- or A5-unsaturated long-chain alcohols and acids has been reported ; intramolecular participation of the alcohol function (after reduction of the acid) in an oxy-mercuration-demercuration sequence affords 2-alkyltetrahydropyranyl and/or 2-alkyltetrahydrofuranyl ethers. K. Nakanishi D. A. Schooley M. Koreeda and I. Miura J. Amer. Chern. SOC.,1972 94 2865. D. N. Kirk W. P. Mose and P. M. Scopes J.C.S. Chem. Comm. 1972 81. F. D. Gunstone and R. P. Inglis J.C.S. Chem. Comm. 1972 12. R. S. Atkinson and E. W.Colvin 12 Ethers The catalysed formation of dimethyl ether from hydrogen and carbon dioxide has been rep~rted.'~' Non-bonded 0-0 interactions in straight-chain diethers have been investigated.lg8 13 Sulphur Compounds Low-valency sulphur acids continue to arouse interest.The fundamental yet elusive sulphenic acids (136) have now been generated and trapped (Scheme 24).189 H C0,Me \/ /c=c\ RS(0) H Scheme 24 An analogous route has been de~eloped''~ for the synthesis of the hitherto unknown sulphoxylic acids (1 37) (Scheme 25). /L\ H C0,Me \/ RSS(0) Scheme 25 S. Naito 0. Ogawa M. Ichikawa and K. Tamaru J.C.S. Chem. Comm. 1972 1266. '" M. Mansson Acta Chem. Scand. 1972 26 1707. E. Block J. Amer. Chem. SOC.,1972 94 642. l9' E. Block J. Amer. Chem. SOC.,1972 94 644. Aliphatic Compounds The facile cleavage of alkyl disulphides by silver nitrate and sodium methane- sulphinate provides a new route'" to thiolsulphonate esters (Scheme 26).The reduction of sulphoxides to sulphides with sodium hydrogen sulphite has been R-S-S-R + Ag' 0 1 RSAg + MeS0,SR Scheme 26 subjected1g2 to mechanistic investigation. Convenient methods for the prepara- tion of sulphilimines' 939194 and sulphoximine~~ 94 have been reported. The undeca-1,3,5-trienes present in the essential oil of the seaweed Dicty-opteris could conceivably arise from two new comp~nents'~~ of this oil the disulphide (138) and the thioacetate (139). \ 12 (138) (139) 14 Miscellaneous A MIND0/2 calculation of the reaction path for the methyl isocyanide to acetonitrile rearrangement predictsIg6 a stable triangular intermediate with the properties of a n-complex rather than an ion pair.Ab initio SCF calculations '97 substantiate this proposal. Further MIND0/2 calculation^'^^ have been carried out on the rotational barrier about C-C single bonds; in an ab initio study,lg9 the calculated energies of rotation were rationalized in terms of contributions from three principal effects staggered arrangements of bonds are preferred ;the axis of a lone-pair orbital prefers to be coplanar with an adjacent electron-withdrawing polar bond or orthogonal to an adjacent lone pair ;dipole moment components perpendicular to the internal rotation axis tend to be opposed. '')I M. D. Bentley I. B. Douglass and J. A. Lacadie J. Org. Chem. 1972 37 333. 19' C. R. Johnson C. C. Bacon and J. J. Rigau J. Org.Chern. 1972 37 919. 193 N. Furukawa T. Omata Y. Yoshimura T. Aida and S. Oae Tetrahedron Letters 1972 1619. '94 Y.Tamura K. Sumoto J. Minamikawa and M. 1. Keda Tetrahedron Letters 1972 41 37. '95 R. E. Moore J. Mistysyn and J. A. Pettus J.C.S. Chem. Comm. 1972 326. 196 M. J. S. Dewar and M. C. Kohn J. Arner. Chem. SOC.,1972 94 2704. 19' D. H. Liskow C. F. Bender and H. F. Schaefer J. Amer. Chem. SOC.,1972,94 5178. 19' M. J. S. Dewar and M. C. Kohn J. Amer. Chem. SOC.,1972,94 2699. '99 L. Radom W. J. Hehre and J. A. Pople J. Amer. Chem. SOC.,1972,94 2371. R. S. Atkinson and E. W. Colvin A 'general' route reported"' for the preparation of a-diazoesters (Scheme 27) while successful for ethyl diazoacetate has been found to fail2'' with ethyl a-diazopropionate.R' R' \ \ C=PPh + TosN -+ C=N, / / R202C R202C Scheme 27 G. R. Harvey J. Org. Chem. 1966 31 1587. M. B. Sohn M. Jones jun. M. E. Hendrick R. R. Rando and W. von E. Doering, Tetrahedron Letters 1972 53.