12 Aliphatic Compounds Part (ii) Other Aliphatic Compounds By E. W. COLVIN Chemistry Department University of Glasgow Glasgow G72800 Owing to the virtually exponential growth in the chemical literature the selection of material for this Annual Report is even more subjective than hitherto. The author has attempted to discern and delineate important areas of activity rather than to present a disconnected set of isolated topics. These areas of activity include the following cyclic per-anhydrides and the chemically related a-lactones ;the tetrahedral intermediate in carbonyl substitu- tion reactions and the possible importance of its conformation ; the precise mechanism of asymmetric induction ;enol and enolate anion studies ;the Favor- skii and homo-Favorskii rearrangements ;and the anchimeric intermediacy and the structure of b-halogenoalkyl radicals a controversial topic reminiscent of the classical-non-classical carbonium ion dialogue.1 Carboxylic Acids and Derivatives The intrinsic acidities of some carboxylic acids have been determined' from gas- phase studies. The significant differences in the ionization constants of the diastereoisomeric forms of 2,3-dicarboxylic acids have been discussed in terms of proximity effects between the functional groups2 Exclusive 0-protonation was observed3 in a 'H n.m.r. study of fumaric and maleic acids in strong acids ; diacid esters including oxalic acid derivatives appear to be diprotonated in super-acid media.4 In contrast to acyclic saturated anhydrides protonated (FS0,H-SbF,-SO,) cyclic unsaturated analogues5 do not cleave below 0 "C ;the 0-protonated species formed undergo rapid inter- molecular proton exchange with solvent or excess anhydride even at the lowest accessible temperatures.Continuing interest is apparent in the study of the decomposition of cyclic per- anhydrides. Such species are prepared by the reaction of the corresponding ' R. Yamdagni and P. Kebarle J. Amer. Chem. SOC.,1973 95 4050. N. Purdie and M. B. Tomson J. Amer. Chem. SOC.,1973,95,48. ' J. W. Larsen and P. A. Bouis J. Org. Chem. 1973,38 1415. G. A. Olah and P. W. Westerman J. Org. Chem. 1973,38 1986. ' G. A. Olah Y. K. Mo and J. L. Grant J. Org. Chem. 1973,38 3207 368 Aiiphatic Compounds-Part (ii) Other Aliphatic Compounds diacids or anhydrides with methanesulphonic acid and 98 % H,O ,or with less risk,6 Na,O,.The ketonic products formed in the vapour-phase thermolysis of malonyl peroxides are taken as further evidence7 of the intermediacy of a-lactones (Scheme 1). 1 0 0 1 0.0 + 0+co+co Scheme 1 Adam* has succeeded in isolating a relatively stable or-lactone bis(trifluor0- methy1)acetolactone(1)(Scheme 2) ;although stable at -20 "C this compound a gas at ambient temperatures has t$40cof 8 h. The solvolysis of di-n-butyl malonyl peroxide has been st~died.~ Reagents i 98 % H,O,-MeS0,H. scheme 2 While the propenolide (2) is postulated" as an intermediate in the decomposi- tion of phenyl maleoyl peroxide benzpropiolactone (3) has been synthesized' (Scheme 3) by low-temperature photolysis of phthaloyl peroxide ;this lactone (3) has been proposed as an intermediate (or by-product) in the formation of benzyne from benzenediazonium 2-carboxylate.The preparation' and reactions of P-peroxy-P-propiolactols,cyclic analogues of the a-hydroperoxy Baeyer-Villiger intermediate have been described (Scheme 4). A. H. Alberts H. Wynberg and J. Strating Synthetic Comm. 1973 3 297. M. M. Martin F. T. Hammer and E. Zador J. Org. Chem. 1973,38 3422. W. Adam J.-C. Liu and 0.Rodriguez J. Org. Chem. 1973,38,2269. ' W. Adam and R. Rucktaschel J. Org. Chem. 1972,37,4128. lo M. M. Martin and J. M. King J. Org. Chem. 1973 38 1588. l1 0. L. Chapman C. L. McIntosh J. Pacansky G. V. Calder and G. Orr J.Amer. Chem. SOC.,1973,95,4061. l2 D. H. Gibson H. L. Wilson and J. T. Joseph Tetrahedron Letters 1973 1289. 370 E. W. Colvin Ph hv Scheme 3 / liV Bu'CO H Reagents i H,O,-H'; ii Ph,P;iii H'; iv A or hv. Scheme 4 The powerfully dienophilic nitrosocarbonyl compounds (4) formed by periodate oxidation of hydroxamic acids,I3 can be trapped reversibly with 9,lO-dimethylanthracene; they react efficiently with dienes to form dihydro-1,2- oxazines (Scheme 5). + Reagent i Et,N 10,-; ii u. Scheme 5 '' G. W. Kirby and J. G. Sweeny,J.C.S. Chem. Comm. 1973,704. A Iiphatic Compounds-Part (ii) 0ther Aliphatic Compounds 37 1 Aqueous nitrosation ' of primary a-carbonyl diazo-compounds yields a-carbonyl nitrile oxides (Scheme 6) which undergo rapid 1,3-dipolar addition to olefins.Scheme 6 The migration of a carboxylate group has been detected' in the benzilic-acid-type rearrangement shown (Scheme 7) ;at pH < 10 ester hydrolysis occurs with subsequent rearrangement while at pH > 11.5 the intact ester group migrates with hydrolysis as a second step. n AA C0,Et c0,- +OH 0 ;ccoc YLW2 \* A co2-0 Scheme 7 The relative migratory aptitude of the ethoxycarbonyl residue has been deter-mined for the pinacol rearrangement of 2,3-dihydroxy-esters (Scheme 8) when the order Ph > C0,Et -Et > Me -H was obtained.16 OH OH C0,Et II I Ph-C-C-CO,Et Ph-C-COR id R Scheme 8 A gas-phase electron-diffraction study' of oxalyl chloride has revealed that the molecule exists as a mixture of trans-and gauche- rather than trans-and cis- conformers.The microwave spectrum' of formimide supports the assignment of an asymmetric cis-trans planar conformation (5) in the gas phase. The tetrahedral intermediate involved in carbonyl-substitution reactions has been the subject of considerable attention. Studies have been described of l4 H. Dahn B. Favre and J.-P.Leresche Helv. Chim. Acra 1973 56 457. l5 H. Rode-Gowal and H. Dahn Helv. Chim. Acta 1973 56 2070. J. Kagan D. A. Agdeppa and S. P. Singh Helv. Chim. Acta 1972,55 2252; J. Kagan and D. A. Agdeppa ibid. p. 2255. K. Hagen and K. Hedberg J. Amer. Chem. SOC.,1973 95 1003. W. E. Steinmetz J. Amer. Chem. SOC.,1973 95 2777. 372 E.W. Colvin substituent influence^'^ on the lactonization of coumarinic acids and of the kinetic isotope effects2' exhibited by [methoxy-'*O]methyl formate. Based on his earlier studies2 'of the ozonolysis of acetals Deslongchamps22 has considered the possible importance of the conformation of this tetrahedral intermediate. An investigation of the hydrolysis of the cation (6) via the intermediate (7) revealed that the ratio of ester to amide produced varied with the size of R (Scheme 9); this suggests that the two possible conformations (6a) and (6b) lead to intermediates (7) of different conformations which lead in turn to different products for stereo-electronic reasons. He proposes that specific cleavage of a C-0 or C-N bond is allowed only if the other two heteroatoms (0or N) of the tetrahedral intermediate have each a lone-pair orbital orientated antiperi- planar to the bond to be cleaved.The basic hydrolysis of salicoylpyrrole (8) is a rapid reaction (Scheme lo) and intramolecular catalysis depends23 on a pK that is 1.4 units higher than the pK of (8);this higher value is probably the pK of the phenol in the tetrahedral intermediate (9). A further of the ambident nature of the amide group has been reported but last year's controversy over the site of amide protonation has largely abated. Aliphatic amides react2' with anhydrous HF and BF to give stable amide hydrofluoroborates (10). l9 R. Hershfield and G. L. Schmir J. Amer. Chem. SOC.,1973,95 7359. *' C. B. Sawyer and J. F. Kirsch J. Amer.Chem. SOC.,1973 95 7375. * P. Deslongchamps and C. Moreau Canad.J. Chem. 197 1,49,2463 ;P. Deslongchamps C. Moreau D. Frehel and P. Atlani ibid. 1972 50 3402. 22 P. Deslongchamps P. Atlani D. Frkhel and A. Malaval Cunud. J. Chem. 1972 50 3405; P. Deslongchamps C. Lebreux and R.Taillefer ibid. 1973 51 1665. 23 F. M. Menger and J. A. Donohue J. Amer. Chem. SOC.,1973,95,432. 24 J. L. Wong and D. 0.Helton J.C.S. Chem. Comm. 1973 352. S. S. Hecht and E. S. Rothman J. Org. Chem. 1973,38 395. 373 Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 1!11 [iil n N N N U (9) 1L Scheme 10 /OH R'-C BF,-\+ N-R~ I R3 2 Nitriles The role of HCN in the prebiotic evolution of biomolecules such as the purines continues to evoke interest.The thermodynamic and kinetic parameters for the formation of glyconitrile (formaldehyde cyanohydrin) have been determined ;26 since the formation of purines requires free HCN,and that of sugars requires free formaldehyde these parameters are of interest in terms of the possibility of simultaneous prebiotic formation of purines and sugars. Full descriptive detailsz7 have been reported for the synthesis of the HCN tetramer diaminomaleonitrile (1 l) by reduction of diiminosuccinonitrile (12); the reverse oxidative transformation of (11) into (12) has been studied,'* as has the chemical reactivity29 of (12). The effects of exposing dilute aqueous solutions of simple nitriles to low doses of ionizing radiations have been d~cumented.~' 26 G.Schlesinger and S. L. Miller J. Amer. Chem. SOC.,1973,95 3729. '' 0.W. Webster D. R. Hartter R. W. Begland W. A. Sheppard and A. Cairncross J. Org. Chem. 1972 37 4133. 28 J. P. Ferris and T. J. Ryan J. Org. Chem. 1973,38 3302. 29 R. W. Begland and D. R. Hartter J. Org. Chem. 1972,37,4136. 30 I. DraganiC Z. DraganiC Lj. PetkoviC and A. NikoliC J. Amer. Chem. SOC.,1973,95 7193. 374 E. W.Colvin The synthesis and reactions of methyl and ethyl nitrosocyanamide (13) have been reported31 as part of a general study on the carcinogenicity of N-nitroso- compounds. The microwave spectrum of cyanogen isocyanate (14) shows32 that although the molecule is bent there is considerable tendency toward linearity with LCNC = 140". A similar of nitrosyl cyanide (15) showed that this molecule is also bent with LCNO = 114" 43' and more strikingly LNCN = 172"31' f3".R-N-CNI NO NC-NCO NC-NO (13) (14) (15) 3 Ketonesand Aldehydes Ab initio (STO-3G) calculation^^^ on simple aldehydes and ketones have shown that a chiral centre induces a hybridization change in a vicinally unsaturated system ;the carbonyl n-electron cloud becomes dissymmetric the electron density being greater on one diastereotopic face than the other. This suggests that orbital factors may be at least partly responsible for asymmetric induction ; indeed neglecting steric factors results similar to those predicted by the rules of Cram Cornforth and Prelog were obtained. Ashby3' has presented a new slant on the stereochemistry of addition of Grignard reagents to carbonyls ;stereochemical control is derived from a balance between steric approach control and a 'compression effect' of the complexed carbonyl in the six-centred transition state against for example the 2,6-diequa- torial hydrogens in cyclohexanone.E.s.r. studies36 have shown that 2-alkanonyl radicals e.g. (16) are stabilized by the contributing allylic structure e.g. (17) to the extent of cu. 15 %. The kinetic results and lack of rearrangement observed in the solvolysis of 3-oxotosy!ates (Scheme 11) can be explained by proposing3' 1,4carbonyl participation. 31 S. S. Mirvish D. L. Nagel and J. Sams J. Org. Chem. 1973,38 1325. 32 W. H. Hocking and M. C. L. Gerry J.C.S. Chem. Comm. 1973,47. 33 R.Dickinson G. W. Kirby J. G. Sweeny and J. K. Tyler J.C.S. Chem. Comm. 1973 241. 34 N. T. Anh 0.Eisenstein J.-M. Lefour and M.-E. T. H. Dau J. Amer. Chem. SOC.,1973 95 6146. '' J. Laemmle E. C. Ashby and P. V. Roling J. Org. Chem. 1973,38 2526. 36 D. M. Camaioni H. F. Walter and D. W. Pratt J. Arner. Chem. SOC.,1973,95 4057. J7 P. Hodgson and S. Warren J.C.S. Chem. Comm. 1973 756. Aliphatic Compounds-Part (ii)Other Aliphatic Compounds -(6 (16) (17) CF,CO,H OCOCF Scheme 11 A detailed of Woodward's predictive U.V. rules for enones has been published. While trialkylated enols (18)can be readily isolated the dialkylated analogues3' are considerably more nucleophilic and less basic ;as a consequence intramole- cular alkylation occurs producing the furanone (19) (Scheme 12).H 0Q H (19) I"+ t Scheme 12 The rates of reaction of a variety of halogenating agents with ketone enols have been studied.40 The poor correspondence between the rates and orientation of enolization with orientation of acetoxylation in the reaction of lead tetra-acetate 38 A. Bienvenue J. Amer. Chem. SOC.,1973,% 1345. 39 H. M. R. Hoffmann and E. A. Schmidt Angew. Chem. Internat. Edn. 1973,12,239. 40 N. C. Den0 and R. Fishbein J. Amer. Chem. Soc. 1973,95 7445. 376 E. W.Colvin with unsymmetrical ketones is taken as evidence4' that enolization may not be the rate-determining step. The suggestion that the direct reaction of bromine with unenolized ketone may be a major pathway in ketone halogenation has been strongly refuted4* in a study in which no measurable dependence of the rate of bromine consumption on bromine concentration was detected.The orientation of halogenation of unsymmetrical ketones with halogen in carbon tetrachloride depends on the halogen used indi~ating~~" that halogen or halide is involved in the enolization step ;the application436 of this observation to the chlorination of ketals has been studied as a facile route to chloromethyl ketones. Swain's44 product study of the orientation of alkaline halogenation of butan-2- one has received kinetic confirmation4' that C-1 and C-3 are attacked equally rapidly. Despite the relative inertness of the monosubstitution products formed in the halogenation of ketones to further halogenation a,a'-disubstitution is frequently observed ;evidence has been presented46 for the following mechanism (Scheme 13).R = H or Ac. Scheme 13 Activation parameter^^^ determined for the bimolecular substitution reactions of a-halogenoketones support the conclusion that only those a-halogenoketones which are stereochemically disposed for carbonyl conjugation or bridging in the transition state undergo substitution by a mechanism significantly different from that operating in the corresponding reactions of alkyl halides. House4* has delineated the parameters required to optimize either C-or 0-acylation of enolate ions. A CND0/2 study4' of the orientation of base-induced ketone alkylations provided satisfactory predictions for all but alkyl-cycloalkyl cases.Speculation continues on the mechanistic ambiguities of the Favorskii re- arrangement. The ratio of diastereoisomeric esters (20) and (21) produced on 41 S. Moon and H. Bohm J. Org. Chem. 1972,37,4338. 42 J. W. Thorpe and J. Warkentin Canad. J. Chem. 1972 50 3229; R. A. Cox and J. Warkentin ibid. p. 3233; R. A. Cox J. W. Thorpe and J. Warkentin ibid. p. 3239; R. A. Cox and J. Warkentin ibid. p. 3242. 43 (a) Y. Jasor M. Gaudry and A. Marquet Bull. SOC.chim. France 1973 2732; (6) ibid. p. 2735. 44 C. G. Swain and R. P. Dunlap J. Amer. Chem. SOC.,1972,94 7204. 45 A. C. Knipe and B. G. Cox J. Org. Chem. 1973,38 3429. 46 K. E. Teo and E. W. Warnhoff J. Amer. Chem. SOC.,1973,95 2728. 47 J. W. Thorpe and J. Warkentin Canad.J. Chem. 1973,51,927. 48 H. 0. House R. A. Auerbach M. Gall and W. P. Peet J. Org. Chem. 1973,38 514. 49 M.-E. T. H. Dau M. Fetizon and N. T. Anh Tetrahedron Letters 1973,851,855. Aliphatic Compounh-Part (ii) Other Aliphatic Compoundr rearrangement of 2-bromo-4-methyl-4-phenylcyclohexanone varies with meth- oxide ion concentration ;Bordwell’ proposes as part-explanation an equilibra- tion between the two cyclopropanones via the oxyallyl zwitterion as shown (Scheme 14). H 7 Ph Ph’ 1 1 Ph’ C02Me Ph-Q..C02Me Scheme 14 A vinylogous Favorskii rearrangement accountss1 for the formation of 5-chloropenta-2,4-dienoic acid by alkalipe hydrolysis of 5,5,5-trichloropent-3-en-2-one (Scheme 15). c1 \ Cl,CCH=CHCOCH,-+ C=CH-CH \ c1/ 1 /c=o CH J-OR c1 c1 -\ \ CHCH=CHCHCO,R +-C=CH-CHCH,CO,R Cl/ \ c1/ c1 \ C=CH-CH=CHCO,R / H Scheme 15 Treatment of the isomeric propargyl derivatives (22) and (23) with sodium methoxide gave the same ester (24) whereas the methyl analogue (25) of (23) gave the branched ester (26).Kirmse” suggests that intramolecular addition of the intermediate diazotate to the triple bond initiates a Favorskii reaction 50 F. G. Bordwell and J. G. Strong J. Org. Chem. 1973,38 579. 51 A. Takeda and S. Tsuboi J. Org. Chem.. 1973,38 1709. 52 W. Kirmse A. Engelman and J. Heese,J.. Amer. Chem. SOC.,1973 95 625. 378 E. W.Colvin (Scheme 16); if R can stabilize an adjacent negative charge as with phenyl the linear ester is produced otherwise one gets branched-chain products.The possible major intermediacy of an oxyallyl zwitterion was excluded by use of chiral substrates when inversion and not racemization was observed. PhCr CCH,N(NO)CONH (22) PhCH,CH,CO,Me HCrCCH(Ph)N(NO)CONH (24) ’i (23) HCrCCH( Me)N(NO)CO,Me -Me,CHCO Me (25) (26) -0-N ’*’;?R-0 I J r’ RCH,CH,CO,Me RCHC0,Me I Me Scheme 16 While the mechanism of the homo-Favorskii reaction exemplified in Scheme 17 is still unknown the possibility of a keten such as (27) being involved has been excluded by two groups,’ 334 although (27) if independently generated will indeed cyclize’’ to the product (28). 4 Alcohols Two proposed oxidation intermediates have been trapped or detected The cyclic manganate ester (29),assumed to be formed in the oxidation of olefins to ’ R.H. Bisceglia and C. J. Cheer J.C.S. Chem. Comm. 1973 165. 54 S. Wolff and W. C. Agosta J.C.S. Chem. Comm. 1973 771. 55 S. W. Baldwin and E. H. Page J.C.S. Chem. Comm. 1972 1337. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds m (27) Scheme 17 diols (Scheme 18) has now been detected spectrophotometrically by two gro~ps.~~*~' R = Me or Ph (29) Scheme 18 While the [2,3]-sigmatropic rearrangement in the proposed mechanistic sequence (Scheme 19) for selenium dioxide oxidation of olefins to allylic alcohols has received some support,58 evidence substantiating the initial ene reaction has been lacking. Such evidence has now been provided by the trapping5' of the selenic acid (30) as the lactone (31).Chiral 1-deuterio-alcohols have been subjected to considerable study. An enzyme exchange method has been reported6' for the preparative-scale synthesis of both (1R)-and (1s)-monodeuteriopropanol.The chirally complexed deuteride reagent (32)affords predominantly6 'the (S)enantiomer on reducing an aldehyde. An n.m.r. method for the determination of enantiomeric purity6' and of the absolute configuration62 of such compounds has been described. 56 D. G. Lee and J. R. Brownridge J. Amer. Chem. SOC.,1973,95 3033. 57 K. W. Wiberg C. J. Deutsch and J. R&k J. Amer. Chem. Suc. 1973,95 3034. K. B. Sharpless and R. F. Laver J. Amer. Chem. Suc. 1972,94,7154. 59 D. Arigoni A. Vasella K.B. Sharpless and H. P. Jensen J. Arner. Chem. SOC.,1973 95 7917. 6o H. Gunther F. Biller M. Kellner and H. Simon Angew. Chem. Internat. Edn. 1973,12 146. 61 C. J. Reich G. R. Sullivan and H. S. Mosher Tetruhedrun Letters 1973 1505. 62 H. Gerlach and B. Zagalak J.C.S. Chem. Cumm. 1973 274. 380 E. W. Colvin H 0’ (30) f X Y = OH OAc or OR (31) Scheme 19 LiA1D.J OR*Iz (32) R*H = ( +)-(2S,3R)-4-dimethylamino-3-methyl-1,2-diphenylbutan-2-ol A gas-chromotographic modification6 of Horeau’s method for the determina- tion of absolute configuration of secondary alcohols has been reported. Brewster’s optical-rotation rules have been modified64 to allow their application to tertiary alcohols. It has been confirmed that the gas-phase acidity order6’ for simple alcohols is the reverse of the solution order solvent assuming a major role in determining relative acidities.5 Amines and Derivatives In a continuing study of amine gas-phase basicities it has been found66 that proton-bridged 1’2-diaminoethane shows a large strain energy inferring that the N...H+...N bond tends to be linear. The utility of the induced Cotton effect for chirality determination of alcohols has found extension as was predicted to simple amines ad cyclic 1,2-amino-alcohols. 67 63 C. J. W. Brooks and J. D. Gilbert J.C.S. Chem. Comm. 1973 194. 64 R. M. Carman Austral. J. Chem. 1973 26 879. 65 R. T. McIver J. A. Scott and J. M. Riveros J. Amer. Chem. SOC.,1973,95 2706. 66 R. Yamdagni and P.Kebarle J. Amer. Chem. SOC.,1973,95 3504. 67 G. N. Mitchell and F. I. Carroll J. Amer. Chem. SOC.,1973 95 7912. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds 38 1 Semi-empirical MO calculations6* on nitrenium ions have shown that for R,N+ singlet-triplet interconversion should occur readily as the energy separation is small ; the exclusive triplet reactivity69 of piperidine nitrenium ion can be rationalized on this basis. The preparation7' of several stable acyl t-butyl nitroxyl radicals has been described (Scheme 20). I Bu' Bu' R = OEt Ph p-PhC,H, or Me(CH,), Scheme 20 INDO evidence has been presented'l for the conformation of the NO group in symmetrical nitroxyl radicals ; the results obtained are consistent with a non-planar rapidly inverting NO group the minimum-energy conformation having an out-of-plane angle of 35".Ab initio SCF computations on the interconversion of ammonium oxide with hydroxylamine have revealed72 a non-least motion path bearing some resem- blance to the allowed motion for a [ 1,3]-sigmatropic shift ; the interconversion is opposed by a considerable activation energy apparently derived from a weaken- ing of the NO bond in the transition state. The out-of-plane rotational mechanism for oxime anion syn-anti isomerization seems unlikely. Peroxyacetyl nitrate (PAN) the simplest member of a class of compounds formed in photochemical smog has had its chemical reactivity investigated. PAN reacts with primary amines and ammonia to give amide~,~~ and it oxidizes aldehydes to The syntheses of t-butyl and methyl peroxynitrate (Scheme 21) have been reported ;76 although alkyl peroxynitrates have not been detected ROOH + N,O -+ ROONO + HNO R = Bu' or Me Scheme 21 68 G.F. Koser J.C.S. Chem. Comm. 1973 461. 69 P. G. Gassman and G. D. Hartman J. Amer. Chem. SOC.,1973,95 449. 70 M.. J. Perkins and P. Ward J.C.S. Chem. Comm. 1973 883. " A. Rassat and P. Rey Tetrahedron 1973 29 1599. '* C. Trindle and D. D. Shillady J. Amer. Chem. SOC.,1973 95 703. 73 E. J. Grubbs D. R. Parker and W. D. Jones Tetrahedron Letters 1973 3279. l4 P. H. Wendschuh H. Fuhr J. S. Gaffney and J. N. Pitts J.C.S. Chem. Comm. 1973 74. 75 P. H. Wendschuh C. T. Pate and J. N. Pitts Tetrahedron Letters 1973 2931. 76 E.F. J. Duynstee J. G. H. M. Housmans J. Vleugels and W. Voskuil Tetrahedron Letters 1973 2275. 382 E. W. Coluin so far in such smog the derived alkyl peroxy-radicals undoubtedly play a large part in its production. 6 Halides Controversy continues over the structure of P-halogenoalkyl radicals. There seems little doubt of their intermediacy in the transition state for the photo- bromination of alkyl bromides :Ske1177 proposes the pathway shown in Scheme 22 to explain an anchimeric assistance of ca. lo3 when compared to the photo- bromination of alkanes; the activation energy is lowered and the activation entropy is more negative as required by the bridging mechanism. # Scheme 22 Explanations of the apparently increased stability of these radicals as compared to simple alkyl radicals have involved either bridged structures (33) or radicals existing in a preferred conformation (34) allowing hyperconjugative stabilization by halogen.Based on kinetic and racemization data it has been suggested78 that in the 2-bromoethyl radical the Br atom is either centred between the two extreme positions or it moves between them with a frequency in excess of 101's-'. However CIDNP studies have inferred7' that the ground state for this radical has non-equivalent methylene groups suggesting (34) although (33) may well be involved in the transition state leading to it; interconversion of methylene groups by bromine migration cannot occur at a rate greater than the rate of diffusion from the cage.E.s.r. spectroscopy f~rther'~ evidence that the 2-chloroethyl radical has the unsymmetrical structure (34). The first e.s.r. spectrum assignable to an or-iodo-radical(35) has been reported.82 The cyclization of the 3-iodopropyl radical to cyclopropane probably proceeds 77 K. J. Shea D. C. Lewis and P. S. Skell J. Amer. Chem. SOC.,1973,95 7768. '* P. S. Skell R. R. Pavlis D. C. Lewis and K. J. Shea J. Amer. Chem. Soc. 1973 95 6735. '' J. H. Hargis and P. B. Shevlin J.C.S. Chem. Comm. 1973 179. 8o J. Cooper A. Hudson and R. A. Jackson Tetrahedron Letters 1973 831. 81 K. S. Chen I. H. Elson and J. K. Kochi J. Amer. Chem. SOC.,1973 95 5341. 82 G. W. Neilson and M. C. R. Symons J.C.S. Chem. Comm. 1973 717. Aliphatic Compounds-Part (ii) Other Aliphatic Compounds via a unimolecular carbon radical displacement ; the unimolecular alternative of a symmetrically bridged limiting structure is considered' unlikely.I~HCONH (35) Earlier attempts to form six-membered cyclic halonium ions from 1,Sdihalides gave exclusive rearrangement to five-membezed rings ;an alkylative route has been rep~rted'~ to such species which are produced in very high proportion from 1 ,Sdi-iodopentane and as major products from 1,5-dibromopentane (Scheme 23). f 65 35 Reagents i MeF-SbF,-SO,. Scheme 23 The preparation of the four-membered cyclic bromonium ion (36) has been described,' as has the preparation86 of dimethylbromonium hexafluoroanti- monate (37) which is stable at ambient temperatures.FCH (MeBrMe)+SbF,-FCH (37) (36) I3Cn.m.r. studies8' on cyclic halonium ions have been described ;temperature-dependent 13C chemical shifts can be used as indicators of the equilibrium8' between cyclic halonium ions and acyclic carbonium ions. 13' R. F. Drury and L. Kaplan J. Amer. Chem. SOC.,1973,95 2217. '* P. E. Peterson B. R. Bonaua and P. M. Henrichs J. Amer. Chem. SOC.,1973 95 2222. 85 J. H. Exner L. D. Kershner and T. E. Evans J.C.S. Chem. Comm. 1973 361. 86 G. A. Olah and J. J. Svoboda Synthesis 1973 203. " B. R. Bonaua and P. E. Peterson J. Org. Chem. 1973 38 1010. P. M. Henrichs and P. E. Peterson J. Amer. Chem. SOC.,1973 95 7449. 384 E. W. Colvin 7 Sulphur The first example of optical activity due to isotopic dissymmetry of carbon has been achieved in the synthesis*’ of the sulphoxide (38),which has = +0.71.”CH,Ph 0-S-13CH2Ph While earlier H n.m.r. evidence suggested that protonation of sulphoxides occurs on sulphur 13Cn.m.r. resultsg0 show protonation on oxygen in accord with i.r. and acid-base equilibrium studies. The similarity of sulphonyl sulphur and carbonyl carbon as electrophilic centres has been exemplified” in a study of their relative reactivity towards a number of nucleophiles. 8 Miscellaneous A number of theoretical st~dies~~*’~*’~ on asymmetric induction have been reported. Optical resolution by differential complexation has been achieved with the designg4 of chiral host molecules whose resolution involves only stability differences in solution of diastereoisomeric complexes.Enzyme-analogue chiral polymersg5 have been described as has their use as resolving agents. Hudson96 has expounded a perturbation theory of reactivity as an alternative to transition-state theory ; based on the general hypothesis that the initial per- turbation determines the course of a reaction such apparently diverse concepts as the symmetry rules for cyclic processes and the theory of hard and soft acids and bases can be derived. A photoelectron-spectroscopic studyg7 of the MO sequence in diazo-com- pounds has revealed that the highest occupied level is the non-bonding b2(n) orbital. An LCAO-MO-SCF calculation on the Wolff rearrangement (Scheme 24) has indicated’* that the postulated oxiren (39) and formyl carbene (40) have almost identical energies both ca.70 kcal mol- less stable than keten ;a related study suggests9’ that keten tends to protonate on the b-carbon. 89 K. K. Andersen S. Colonna and C. J. M. Stirling J.C.S. Chem. Comm. 1973 645. 90 G. Gatti A. Levi V. Lucchini G. Modena and G. Scorrano J.C.S. Chem. Comm. 1973,251. 91 J. L. Kice and E. Legan J. Amer. Chem. SOC.,1973,95 3912. 92 L. Salem J. Amer. Chem. Soc. 1973,95 94. 93 G. R. Franzen and G. Binsch J. Amer. Chem. SOC.,1973 95 175; R. D. Norris and G. Binsch ibid. p. 182; G. Binsch ibid. p. 190. 94 R. C. Helgeson K. Koga J. M. Timko and D. J. Cram J. Amer. Chem. SOC.,1973 95 3021 ; R. C. Helgeson J. M. Timko and D. J. Cram ibid. p. 3023. 95 G. Wulff A. Sarhan and K. Zabrocki Tetrahedron Letters 1973 4329.96 R. F. Hudson Angew. Chem. Internat. Edn. 1973 12 36. 97 E. Heilbronner and H.-D. Martin Chem. Ber. 1973 106 3376. 98 A. C. Hopkinson J.C.S. Perkin II 1973 794. 99 A. C. Hopkinson J.C.S. Perkin II 1973 795. Aliphatic Compounds-Part (ii)Other Aliphatic Compounds R',k2= H (40) R' )=c=o R' R2 AR2 Scheme 24 Reviews have been published on slow proton-transfer reactions,' O0 isocyan-ates,"' phosgene,'" and the structures and chemistry of the macrolide anti- biotics.'O3 A vigorous warning has been sounded in a variety of publications on the extreme carcinogenic hazards of handling bis(chloromethy1) ether. loo R. E. Barnett Accounts Chem. Res. 1973,6,41. S.Ozaki Chem..Rev. 1972 72,457. lo' H. Babad and A.G. Zeiler Chem. Rev. 1973,73 75. Io3 W. Keller-Schierlein,Forrschr. Chem. org. Nuturstofe 1973 30,3 13.