10 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By E. W. COLVIN Chemistry Department University of Glasgow Glasgow G 12 800 The major areas of activity over the past year include the following :continuing detailed studies of the tetrahedral intermediate involved in carbonyl substitution reactions and the not unrelated topic of the protonation site of amides; the proof and spatial definition of front octants for ketones (see chapter 2 p. 37); amplification of the exciton chirality method for configuration determination ; and more structural studies on P-halogeno-alkyl radicals. 1 Carboxylic Acids From measurements of gas-phase equilibria the intrinsic acidities of a- p- and y-chloro-substituted aliphatic acids have been evaluated ;’ the effects of the chloro-substituent parallel those in solution but they are much larger the attenuation in solution is attributed to weaker H-bonding of the chloro-stabilized acid anions to water molecules.Related studies have been carried out on substi- tuent effects on the intrinsic acidities of benzoic acids,’ and on the intrinsic acidities of carbon acids.3 Some of the techniques and results of gas-phase acidity and basicity determinations have been re~iewed.~ 2 Peracids The preparations of a number of new peracids have been described and their epoxidizing abilities have been delineated. 0-Benzylmonoperoxycarbonic acid (1) is quite stable in the cold and shows’ reactivity intermediate between those of m-chloroperbenzoic acid and perbenzoic acid the last having now been prepared on a polymer support.6 The peroxycarbamic acids (2) and (3) have been generated in situ (3) having been isolated and crystallized ;’both efficiently convert olefins into epoxides with concurrent production of innocuous by- products.‘ R. Yamdagni and P. Kebarle Canad. J. Chem. 1974,52 861. R. Yamdagni T. B. McMahon and P. Kebarle J. Amer. Chem. Soc. 1974,96 4035. T. B. McMahon and P. Kebarle J. Amer. Chem. Sac. 1974,96,5940. C. Agami Bull. SOC.chim. France 1974 869. R. M. Coates and J. W. Williams J. Org. Chem. 1974 39 3054. C. R.Harrison and P. Hodge J.C.S. Chem. Comm. 1974 1009. ’ J. Rebek S. F. Wolf and A. B. Mossman J.C.S. Chem. Comm. 1974 71 1. 269 270 E. W. Colvin Evidence has been presented* for the intervention of the 1,4-biradical l-oxa- tetramethylene (4) in the thermodecarboxylation of y-peroxy-lactones.0 3 Carboxylic Acid Anhydrides A dynamic n.m.r. spectroscopic investigationg of formic anhydride has revealed the EZ-configuration (5) in solution in accord with gas-phase electron-diffraction data; the low barrier (18$_1 kJmol-') for topomerization is taken as further evidence for the diminished importance of resonance in anhydrides in comparison to esters and imides. The conformations of some gem-dimethyl-substituted cyclic anhydrides have been determined." 4 Lactones While the n-+ T* Cotton effect of A2-butenolides is easily influenced by asym- metry external to the lactone ring the chirality at the y-carbon of the butenolide is the sole sign-determining factor in the 71 +T* c.d.spectrum ;the latter absorp- tion is therefore recommended' for the determination of absolute configuration of A2-butenolides. If X is greater than Y in polarizability then lactone (6) will show a negative effect and uice oersa. Equilibration studiesI2 on a number of 2,4-disubstituted y-butyrolactones have indicated that the cis-stereoisomer is the thermodynamically more stable in all cases. Detailed kinetic and mechanistic studiesI3 of the alkaline hydrolysis of a variety of lactone ring sizes have been reported in detail. W. Adam and L. M. Szendrey J. Amer. Chem. SOC.,1974,96,7135 ;see also W. Adam Angew. Chem. Internat. Edn. 1974 13 619. E. A. Noe and M. Raban J.C.S. Chem. Comm. 1974,479. ' G.Borgen Acta Chem. Scand. 1974 B28 13. I. Uchida and K. Kuriyama Tetrahedron Letters 1974 3761. S. A. M. T. Hussain W. D. Ollis C. Smith and J. F. Stoddart J.C.S. Chem. Comm. 1974,873. l3 G. M. Blackburn and H. L. H. Dodds J.C.S. Perkin If 1974 377; see also M. Balak-rishnan G. V. Rao and N. Venkatasubramanian ibid. p. 1093. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 271 A number of naturally occurring lactones and tetronic acids have been synthe- sized or have had their syntheses improved. These include tetronic acid14 itself and some 5-carboxymethyltetronic acids,' including (S)-carlosic acid' (7). Pestalotin'7.'8 (€9,a synergist of gibberellins and ~trigol'~-~' (9) a germination stimulant of witchweed seeds have both yielded to elegant total syntheses.OH OH 5 a-Amino-acids Information regarding the rotamer populations of amino-acids can be obtained by considering the '3C-C-C-H coupling constant22 between the or-CO,-and the p-protons. A second chlorine-containing natural (L)-amino-acid (10) has \mco2-CI NH been isolated :2 optically pure vinylglycine has been synthe~ized.~~ 14 J. V. Greenhill and T. Tomassini Tetrahedron Letters 1974 2683. 15 A. Svendsen and P. M. Boll Tetrahedron Letters 1974 2821. 16 J. L. Bloomer and F. E. Kappler J. Org. Chem. 1974 39 I 13. 17 R. M. Carlson and A. R. Oyler Tetrahedron Letters 1974 2615. 18 D. Seebach and H. Meyer Angew. Chem. Internat. Edn. 1974 13,77. 19 J. B. Heather R. S. D. Mittal and C. J. Sih J. Amer. Chem.SOC.,1974,% 1976. 20 G. A. MacAlpine R. A. Raphael A. Shaw A. W. Taylor and H.-J. Wild J.C.S. Chem. Comm. 1974,834. 21 See also J. M. Cassady and G. A. Howie J.C.S. Chem. Comm. 1974 512. 22 J. Feeney P. E. Hansen and G. C. K. Roberts J.C.S. Chem. Comm. 1974 465. 23 S.-I. Hatanaka S. Kaneko Y.Niimura F. Kinoshita and G. Soma Tetrahedron Letters 1974 3931. 24 P. Friis P. .Helboe and P. 0. Larsen Acta Chem. Scand. 1974 B28,317. 272 E. W. Coluin RyCoz-Ac,O ”-,/’. I PY I NH,’ NHAc Scheme 1 Kinetic and mechanistic studies on the Dakin-West reaction (Scheme 1) have convinced Allinger’’ that the oxazolone mechanism alone is in accord with the experimental facts on this transformation. A chiral host molecule capable of achieving the total optical resolution of amino-acid ester salts by specific molecular complexation has been described.26 6 Carboxylic Acid Amides Although there is now considerable evidence for the formation of a tetrahedral intermediate in carbonyl substitution reactions the instability of this inter- mediate and the complicated kinetics of its simultaneous formation and break- down have precluded much detailed analysis.It has now been reported2’ that the reaction of the imidate cation (1 1) with nucleophiles proceeds via the stable tetrahedral species (12) permitting a thorough mechanistic study. An ab initio studyz8 of the reactivity of aminodihydroxymethane has provided theoretical evidence for the operation of marked stereoelectronic effects sub- 25 N.L. Allinger G. L. Wang and B. B. Dewhurst J. Org. Chem. 1974 39 1730; see also J. Lepschy G. Hofle L. Wilschowitz and W. Steglich Annulen 1974 1753. 26 L. R. Sousa D. H. Hoffman L. Kaplan and D. J. Cram J. Amer. Chem. SOC.,1974 96 7100; see also J. M. Timko R. C. Helgeson M. Newcomb G. W. Gokel and D. J. Cram ibid. p. 7097; M. Newcomb R. C. Helgeson and D. J. Cram ibid. p. 7367. 2’ N. Gravitz and W. P. Jencks J. Amer. Chem. SOC.,1974,96 489 499 507. J. M. Lehn and G. Wipff J. Amer. Chem. SOC.,1974,96,4048. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 273 stantiating Deslongchamps' postulate2' that the direction of cleavage of the tetrahedral intermediate is controlled by lone-pair orbitals being orientated antiperiplanar to the bond being cleaved.The comparison of imidate and amide hydrolysis in concentrated acids may be unwarranted evidence having been presented3' that 0-alkyl cleavage occurs in the imidate case neutral amide H,O -Me '*O + II hi+ -+ H,O-Me + PhCNHMe II C Ph /\ NHMe Scheme 2 being the leaving group (Scheme 2). Other studies of amide3' and thi~amide~~ hydrolysis have been reported. The stereochemistry of open-chain O-methyl- imidates and large-membered cyclic lactim ethers has been revised33 to E. RTo 0 (13) From a careful study of the two sets of amides (13) and (14) using criteria such as ring size electronic effects change in hybridization during reaction and conjugation Kre~ge~~ has discounted N-protonated conjugate acids not only as the principal products of equilibrium protonation of amides in dilute and moderately concentrated aqueous acids but also as essential intermediates in acid-catalysed amide hydrolysis.The predominant protonated form of DMF in aqueous acid is the 0-protonated amide a doublet methyl signal being observed3' by I3Cn.m.r. spectroscopy at all acidities. Further evidence has been presented36 for S-protonation of primary thioamides. Liler3 has published full details of her work on the site of protonation of benzamide and has promised a detailed response to the many critics of N-protonation. 29 P. Deslongchamps P. Atlani D. Frthel and A. Malaval Canad. J. Chem. 1972 50 3405; P.Deslongchamps C. Lebreux and R. Taillefer ibid. 1973 51 1665. 30 R. A.McClelland J. Amer. Chem. SOC.,1974 96 3690. 3' B. C. Challis and S. P. Jones J.C.S. Chem. Comm. 1974 748. 3z A. J. Hall and D. P. N. Satchell Chem. and Ind. 1974 527. 33 C. 0.Meese W. Walter and M. Berger J. Amer. Chem. SOC.,1974,96 2259. 34 A. J. Kresge P. H. Fitzgerald and Y. Chiang J. Amer. Chem. SOC.,1974,96 4698. 35 R. A. McClelland and W. F. Reynolds J.C.S. Chem. Comm. 1974 824. 36 W. Walter M. F. Sieveking and E. Schaumann Tetrahedron Letters 1974 839. 3' M. Liler J.C.S. Perkin ff 1974 71. 274 E. W. Colvin A spectroscopic investigation3* has shown that while bistrimethylsilylform- amide has the amide structure (15) all other bistrimethylsilylamides studied are in the imidate form (16). An ab initio study of hydrogen bonding involving the amide linkage has been rep~rted,~’as has an n.m.r.spectroscopic study4’ of hydrogen exchange in on have amidiurn ions. Hartree-Fock SCF calc~lations~~ amido-radi~als~~ predicted the TI ground state (17) in accord with e.s.r. spectroscopic assignments. 7 Ketones and Aldehydes An ab initio study43of nucleophilic addition to the carbonyl group has pro- duced results in qualitative agreement with those derived from solid-state data. A similar of the protonation of the carbonyl group gave a basicity order of amide > carboxylic acid > acid fluoride ‘Y acetaldehyde > keten > form-aldehyde an order which closely follows the degree of negative charge on oxygen. Gas-phase ionic reactions related to acid-catalysed carbonyl reactions in solution have been studied4’ by ion-cyclotron resonance.Cyclohexanone and acetophenones form complexes with AgBF in dichloro- methane as shown46 by the enhanced solubility of the silver salts. I3C n.m.r. spectroscopic evidence indicated that the carbonyl group is acting as a n-donor ” C. H. Yoder W. C. Copenhafer and B. DuBeshter J.Amer. Chem. SOC.,1974,96,4283. 39 A. Johansson P. Kollman S. Rothenberg and J. McKelvey J. Amer. Chem. SOC. 1974,96 3794. 40 C. L. Perrin J. Amer. Chem. SOC.,1974 96 5629 5631. 41 T. Koenig J. A. Hoobler C. E. Klopfenstein G. Hedden F. Sunderman and B. R. Russell J. Amer. Chem. SOC.,1974 96 4573. 42 J. N. S. Tam R. W. Yip and Y. L. Chow J. Amer. Chem. SOC.,1974,96,4543,4573 O3 H. B. Biirgi J. M. Lehn and G. Wipff J.Amer. Chem. SOC.,1974,96 1956. 44 A. C. Hopkinson and I. G. Csizmadia Cunud.J. Chem. 1974,52,546; see also A. Levi G. Modena and G. Scorrano J. Amer. Chem. SOC.,1974 96 6585; D. G. Lee and M. H. Sadar ibid. p. 2862. 45 J. K. Pau J. K. Kim and M. C. Caserio J.C.S. Chem. Comm. 1974 120 121. 46 D. R.Crist Z.-H. Hsieh G. J. Jordan F. P. Schinco and C. A. Maciorowski J. Amer. Chem. SOC.,1974,96,4932. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds giving a rather weak Ag-0 bond (18); no evidence of syn-anti isomerism could be detected even at low temperatures. (18) The resolution of ketones and the determination of their specific rotation via formation of the corresponding dioxolans with chiral 1,Zdiols have been des- ~ribed.~’3C n.m.r.chemical shifts of carbonyl and thiocarbonyl groups have been ~orrelated.~’ Harris49 has published a welcome review of his work on the synthesis of p-polycarbonyl systems and their cyclization to polyketide metabolites. The 6-tetraketone (19) has been prepared5’ and identified with ‘Harris’s tetraketone’ isolated in 1914 by degradation of caoutchouc. Dioxocarboxylic acids which occur in significant amounts in plant cuticular lipids can be readily obtained5’ by alkylation of acetylacetone dianion with m-bromoalkanoates (Scheme 3). Scheme 3 Acetylacetone forms two isomeric enol acetates (20) and (21) both in the (S)-cis-conformation in approximately equal proportions (Scheme 4);the stability (20) Scheme 4 47 J. Y. Conan A. Natat F. Guinot and G.Lamaty Bull. SOC. chim. France 1974 1400 1405; Tetrahedron Lerters 1974 1667; J. Brugidou H. Christol and R. Sales Bull. Soc. chim. France 1974 2027,2033. 48 H.-0. Kalinowski and H. Kessler Angew. Chem. Internat. Edn. 1974 13 90. 49 T. M. Harris C. M. Harris and K. B. Hindley Fortschr. Chem. org. Nafurstoffe 1974 31 217. B. Franck V. Scharf and M. Schramayer Angew. Chem. Internat. Edn. 1974,13 136. ’’ R. 0.Pendarvis and K. G. Hampton J. Org. Chem. 1974,39,2289. 276 E. W. Coluin of the isomer (20) is attributed5* to some degree of neighbouring-group inter- action a rationale consistent with 'H n.m.r. spectroscopic data. In work based on the conceptually useful analogy between mass spectrometric and anodic chemistry it has been found53 that anodic oxidation of simple ketones in acetonitrile leads to y-hydrogen abstraction with subsequent solvent .z% Hzo* MeCN a,, NHCOMe Scheme 5 capture and/or rearrangement/capture (Scheme 5); no &cleavage is observed.Improved syntheses of m~condialdehyde~~ and t-b~tylmalondialdehyde~ have been described. (S)-(+ )-4-Methylheptan-3-one the principal alarm pheromone of the ant Atta texana has been synthesized in high optical 8 Alcohols Complexing agents such as copper hexafluoroacetylacetonate,are of considerable utility in the determination of absolute configuration of alcohols glycols and related systems by the exciton chirality method,57 which has been demonstrated to be operative5' even at considerable separation of the two interacting chromo- phores ; it has also been applied5' to the chirality determination of conjugated enone ester and lactone benzoates.The absolute configurations of chiral secon- dary alcohols (and amines) can be ascertained6' by a study of the 'H n.m.r. spectra of the derived diastereoisomeric esters (and amides) of or-phenylbutyric and hydratropic acids. Significant preparative-scale resolution of racemic alcohols can be achieved61 via their hippurate esters by selective hydrolysis catalysed by a-chymotry psin. 52 D. V. C. Awang Canad. J. Chem. 1973,51 3752. 53 J. Y. Becker L. R. Byrd and L. L. Miller J. Amer. Chem. Soc. 1974,96,4718. 54 G. Kossmehl and B. Bohn Chem. Ber. 1974 107,710. 55 C. Reichardt and E.-U. Wiirthwein Chem. Ber. 1974,107 3454.56 R. G. Riley and R. M. Silverstein Tetrahedron 1974 30 1171. 57 J. Dillon and K. Nakanishi J. Amer. Chem. SOC.,1974,96,4055 4057,4059. '* S. L. Chen N. Harada and K. Nakanishi J. Amer. Chem. SOC.,1974,96,7352. 59 M. Koreeda N. Harada and K. Nakanishi J. Amer. Chem. Sac. 1974 96,266. 6o G. Helmchen Tetrahedron Letters 1974 1527. 6' Y. Y. Lin D. N. Palmer and J. B. Jones Canad. J. Chem. 1974 52 469. A lip hatic Compo unds-Par t (ii ) 0ther Aliphatic Compounds 277 The average solution conformations of all 18 possible isomers of the six- carbon aliphatic alcohols have been elucidated62 by 'H and 13C n.m.r. spectro- scopic studies. The thermochemistry of some aliphatic alcohols has been studied63 using pulsed ion-cyclotron resonance spectroscopy.The copper-catalysed vapour-phase rearrangement of allylic alcohols to saturated ketones appears64 to proceed by initial dehydrogenation generating a small amount of @-unsaturated ketone. In the rate-limiting step the C-3 hydrogen of the alcohol is transferred to the enone fi-carbon atom (Scheme 6). @-f++-A.(+q/ slow 0 OH 0 OH 0 0 Scheme 6 9 Amines While in most cases correlation of the absolute configurations of chiral amines with results from the Horeau method is valid it has been re~omrnended~~ that such assignments should always be substantiated by direct chemical correlation or by unambiguous c.d. measurements. Bis-2,4-dinitrophenyl derivatives of diamines show66 induced Cotton effects allowing chirality determination ;those with negative C-N chirality show a negative Cotton effect for the longest wave- length band.10 Alkyl Halides Ab initio calculation^^^ on the geometric structure and energy surface of the chloroethyl cation have given results in good agreement with those derived experimentally from super-acid data. Further evidence68 of a bridged transition state in the formation of P-bromoalkyl radicals has been presented. P-Chloro- and /3-bromo-t-butyl radicals (22) and (23) have been generated in a [2H16]adamantane matrix by X-irradiation of isobutyl chloride or bromide at 77 K. E.p.r. spectroscopic studies have shown6' that while radical (22) prefers the same eclipsed conformation (25) as it does in solution radical (23) prefers the staggered conformation (26); radical (23) is much less stable than (22).The analogous /3-fluoro-radical (24) also prefers an eclipsed conformation. 62 K. L. Williamson D. R. Clutter R. Emch M. Alexander A. E. Burroughs C. Chua and M. E. Bogel J. Amer. Chem. SOC.,1974,96 1471. 63 R. T. McIver and J. S. Miller J. Amer. Chem. SOC.,1974 96 4323. 64 G. Eadon and M. Y. Shiekh J. Amer. Chem. Soc. 1974,96 2288. 65 H. E. Smith A. W. Gordon and A. F. Bridges J. Org. Chem. 1974 39 2309. 66 M. Kawai U. Nagai and T. Kobayashi Tetrahedron Letters 1974 1881. 67 W. J. Hehre and P. C. Hibberty J. Amer. Chem. SOC.,1974,96 2665. " E. N. Cain and R. K. Solly J.C.S. Chem. Comm. 1974 148. 6q R. V. Lloyd D. E. Wood and M. T. Rogers J. Amer. Chem. SOC.,1974,96 7130. 278 E. W. Colvin CI Me2CCH2X (22) x = c1 MeH AMe hI@Le (23) X = Br H (24) X = F H (25) (26) N.m.r.spectroscopic studies7' of 2-fluoroethanol have confirmed that the major conformer (95%) is gauche (27); no evidence of intramolecular F-H bonding could be detected. H$? H 11 SulphurCompounds The first example of asymmetric induction promoted by isotopic dissymmetry has been pre~ented.~ Halogenation of the chiral sulphoxide (28) followed by oxidation resulted in optical activity in the a-halogenosulphone (29). CH,Ph PhCD,- S -00 PhCD2S02EHPh IX (28) (29) A further example of the intramolecular transfer of chirality from sulphur to carbon is seen'2 in the Pummerer-type rearrangement of chiral (30) to (31) (Scheme 7). Reagent :i dicyclohexylcarbodi-imide Scheme 7 '* R.C. Griffith and J. D. Roberts Tetrahedron Letters 1974 3499. 'I M. Cinquini and S. Colonna J.C.S. Chem. Comm. 1974 769. '* B. Stridsberg and S. Allenmark Actu Chem. Scand. 1974 BR8 591. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds t-Butyl- and n-butyl-lithium are unsatisfactory bases for the generation of u-sulphinyl carbanions owing to competitive C-S bond cleavage ; the chiral sulphoxide (32) is ra~ernized~~ in a few minutes at -78 "C(Scheme 8). Methyl-lithium or a lithium dialkylamide are much better reagents for such carbanion formation. 0 0 I I Bu'Li + Bu'S*Ar -+ Bu'SAr + Bu'Li (32) Scheme 8 12 Miscellaneous Further detail^'^?^ have been given of the determination of enantiomeric purity by n.m.r.spectroscopy using chiral lanthanide shift reagents. The defensive compound in the frontal-gland secretion of soldier termites has been identified76 as 1-nitro-trans-pentadec-1-ene.The chemistry of hydroxamic acids and N-hydroxy-imide~~~ has been reviewed as has that ofcarbon suboxide:8 C,02 a precursor of inter alia malonic acid derivatives and of halogenovinylene carbonate^.'^ 73 T. Durst M. J. LeBelle R. V. den Elzen and K.-C. Tin Canad. J. Chem. 1974,52,761. 74 M. D. McCrearty D. W. Lewis D. L. Wernick and G. M. Whitesides J. Amer. Chem. SOC.,1974 96 1038. 75 H. L. Goering J. N. Eikenberry G. S. Koermer and C. J. Lattimer J. Amer. Chem. Sac. 1974 96 1493. l6 J. VrkoE and K. Ubik Tetrahedron Letters 1974 1463.77 L. Bauer and 0. Exner Angew. Chem. Internat. Edn. 1974 13 376. 78 T. Kappe and E. Ziegler Angew. Chem. Internat. Edn. 1974 13 491. '' H.-D. Scharf Angew. Chem. Internat. Edn. 1974 13 520.