4 Reaction Mechanisms Part (ii) Polar Reactions By D. J. McLENNAN Department of Chemistry University of Auckland Auckland New Zealand 1 Introduction Several of the most notable 1986 contributions appeared in Symposia-imprint. An issue of Israel Journal of Chemistry (with a 1985 dateline) was devoted to the reactivity-selectivity principle (RSP) whilst Tetrahedron featured an issue on hydride transfer. The Journal ofPhysical Chemistry dedicated an issue to Ruldoph A. Marcus and Arthur N. Bourns was similarly honoured by the Canadian Journal ofchemistry. Discussion of relevant papers will be deferred to the appropriate mechanistic section. If Pross and Shaik have their way there may well be no Polar Reactions subsection in Annual Reports in the near future.Their configuration mixing (CM) model blurs the distinction between ‘polar two-electron’ shifts and radicaloid one-electron trans- fers. Pross has comprehensively reviewed the field and has applied the qualitative theory to a wide variety of reaction types.’ Radical intermediates are not a necessary consequence of the emphasis on one-electron shifts but it is noteworthy that further evidence has been adduced for radical and radical ion intermediates in what were hitherto regarded as ionic reactions. The quantitative aspects of the CM model addressed by Shaik will be covered elsewhere. Even on this basis the concept of effective charge on an atom in a transition state (TS) is still valid insofar as this is the charge ‘seen’ by substituents and solvent.Thea and Williams discuss ways of measuring such charges.2 Ionic reactions are of course not constrained to condensed media and a considerable body of work on gas-phase nucleophilic displacement reactions has been re~iewed.~ Douglas has presented an account of work on elimination-addition pathways for chemical and biochemical reactions of thiol esters4 Nature has played a nasty trick on researchers in this area since some thiol chemistry will always be necessary. Having once dabbled with thiols himself the Reporter appreciates perhaps more than most the apt Shakespearian epilogue to Douglas’s paper. Seeman has reviewed in practical terms the integration of the Curtin-Hammett and Winstein-Holness concept^.^ ’ A. Pross Adu. Phys. Org. Chem. 1985,21,99.’ S.Thea and A. Williams Chem. SOC.Reu. 1986,15,125. J. M. Riveros,S. M. Jose and K. Takashima Adu. Phys. Org. Chem. 1985,21 197. K.T.Douglas Acc. Chem. Rex 1986,19,1986. ’ J. I. Seeman J. Chern. Educ. 1986,63,42. 47 D. J. McLennan Heterolysis of carbon-carbon bonds yields carbanions and carbocations. Arnett and Molter continue their work in this area and have developed a master equation for predicting solution heterolysis energies and re-emphasize that the energetics of anion-cation combination reactions are dominated by ion solvation factors. It is therefore not surprising that a spectacular failure of the RSP is found confirming a Pross prediction of some years ago. Zwitterions are also best discussed in a general mechanistic section.It is somewhat ironic that the debate over one-step (concerted pericyclic) us. two-step 1,3-dipolar cycloaddition reactions previously focused attention on the possibility of biradical intermediates in the stepwise cases. The first clearcut evidence for the stepwise mechanism presented equally ironically by Huisgen is interpreted in terms of zwitterionic intermediates for cases involving high HOMO (1,3-dipole) and low LUMO (dipolarophile) energies.' The cycloadditions in question are non-stereos- pecific7" and intermediates have been intramolecularly tra~ped.~ The rich diversity of mechanistic pathways in nucleophilic vinylic substitution is exemplified in a comprehensive review by Rappoport.8 The search for alternative catalytic methods for routine organic reactions has progressed from the laboratory to the kitchen.The use of microwave ovens acceler- ates common polar reactions in solution by factors up to 250-f0ld.~ Pressure solvent superheating and even solvent boiling point seem to be of importance in determining the magnitude of the accelerations. While kinetic and mechanistic investigations will undoubtedly continue the applicability of the method to large-scale preparations is mandated. Cook-book chemistry may well acquire a new and less derisory dimension. 2 Solvolysis and Carbocations Proton loss from carbocations to yield alkenes and/or fragmentation products is a commonplace occurrence. Loss of a methyl group when for instance (1) yields (2) plus (3) (12 1) in FS03H-S02 at -60°C is less expected." Carr and Whittaker claim that methyl loss as CH3+ competes with methyl migration prior to cyclization and support their proposal by observing that (a) the medium is non-nucleophilic (b) the TS for a shift of methyl from a gem-dimethyl group is highly crowded and (c) CH,03SF has been observed in a similar case.The stability of ethers in super-acid apparently rules out direct attack by the hydroxyl oxygen on methyl. E. M. Arnett and K. Molter J. Phys. Chem. 1986,90 383. '(a) R. Huisgen G. Mloston and E. Langhals J. Am. Chem. SOC.,1986 108 6401; (b) J. Org. Chem. 1986,51 4085. Z. Rappoport Recl. Trau. Chim. Pays-Bas 1985 104 309. R. Gedge F. Smith K. Westaway H. Ali L. Baldisera L. Laberge and J. Rousell Tetrahedron Lett. 1986 27 279.lo G. Cam and D. Whittaker J. Chem. Soc. Chem Commun. 1986 1245. Reaction Mechanisms -Part (ii) Polar Reactions 49 Organic non-carbocations of interest have been reported. The triphenylsilyl cation has been prepared according to equation 1 and the trivial name sityl has been proposed." The methoxydiazonium cation CH30N2+ has been prepared by methyla- tion (MeF-SbF in S02F2 or S02C1F) of N20 and acts as a methylating agent rather than a methoxylating agent towards toluene.12 Attempts to prepare the hydroxy analogue HON2+ were unsuccessful but in any case this cation lacks an essential feature for mention in Section B of Annual Reports. Ph3SiH + Ph3C+C104-+ Ph3Si+C104-+ Ph3Cl (1) Diary1 carbocations destabilized by an a-carbonyl group (4) have been prepared from alcohois using C1S03H and have a reasonable lifetime at low temperature.'' 13 C N.m.r.parameters suggest that the 0x0 structure (5) is not a significant resonance contributor. At ambient temperature these ions form benzofurans or fluorenes by 6 T electrocyclization. Long-range 19F n.m.r. isotope shifts due to y-deuteration in carbocations are upfield whereas the corresponding P-deuterium shifts are d0wnfie1d.I~ This corre- sponds to the situation met with for kinetic and equilibrium isotope effects in carbocation-forming solvolysis which are normal for P-deuterium and inverse for y-deuterium in spite of the differing mechanisms governing the two types of isotope effects. Laser flash photolysis of Ph3COAc allows generation of ground-state Ph3C+ in solution (1:2 MeCN-H20) and reactions of the free carbocation with nucleophiles can be st~died.'~ Water reacts with a rate constant of 1.5 x lo5s-' whilst azide ion is the most reactive of the nucleophiles studied with a rate constant of 4 x lo91 mol-' s-I which is close to the diffusion limit (and close to the indirectly determined calibration value of 5 x lo91 mol-' s-l employed by Jencks and co-workers for the 1-phenylethyl cation).Surprisingly the rate constants for a wide range of nucleophiles do not concur with the pattern established earlier for more stable cations by Ritchie in his development of the N+ nucleophilicity scale. Only azide approaches the diffusional limit. Other good N+ nucleophiles may well be levelling but at rates lo2 below the limit.In any case the RSP is followed when the less reactive An3C+ is compared with Ph3C+. The directly observed azide :water rate ratio is within an order of magnitude of (some of) those established by product analyses. Since azide is the most frequently used of probe nucleophiles for carbo- cation capture its unusual behaviour warrants further attention. '*J. B. Lambert J. A. McConnell and W. J. Schulz J. Am. Chem. SOC.,1986 108 2842. 12 G. A. Olah R. Herges K. Laali and G. A. Segal J. Am. Chem. SOC.,1986 108 2054. 13 L. H. Dao M. Maleki A. C. Hopkinson and E. Lee-Ruff J. Am. Chem. SOC.,1986 108 5237. 14 D. A. Forsythe J. S. Puckace and F. E. Shawcross Tetrahedron Lett. 1986 27 3569. l5 R. A. McClelland N.Banait and S. Steenken J. Am. Chem. SOC.,1986 108 7023. 50 D. J. McLennan Carbonate ion is only 1.7 times less reactive towards (pmethoxypheny1)tropylium cation than is hydroxide ion,I6 which suggests caution in the use of C032-HC03- buffers in the investigation of reactive electrophiles. When more reactive nucleophiles are involved there is no problem but it is still an open question as to whether desolvation ion pair formation or covalent bond formation is the rate-limiting step in anion-cation reactions. In the case of methoxide reaction with 2,6-di-t-butyl-4- arylthiopyrylium cations adduct formation appears to be rate-limitir~g,’~ but this may not be a general rule. The solvolysis chemistry of the 1-phenylethyl system continues to be of interest even though the pioneering studies date back to the work of Ingold and Hughes in the 1930s.A paper entitled ‘Anatomy of an SN1 Reaction’ receives the 1986 award for the most eye-catching title although it will not enjoy the readership of other anatomical studies commonly featured on page three of tabloid newspapers. It does however extend the studies of Jones and Kirby on the relationship between crystal structure parameters and reactivity in solution to the S,1 reactions of ArCH(CH3)0X systems wherein aryl and X substituents are varied.18 The response of crucial bond lengths and angles to substitution allows a picture of the early stages of C...OX heterolysis to be described. Two simple and general rules arising from earlier work of a similar nature remain valid (i) the longer the bond in a given system the faster it breaks and (ii) the more reactive the system the more sensitive is the length of the bond to structural variation.In past decades structure and mechanism have been viewed as almost separate concepts although biochemists and catalysis researchers have long known otherwise. The attentions of chemists have been increasingly directed towards a unification in recent years and the time may well come when the diffractometer is viewed as being as much an instrument for mechanis- tic studies as is the fixed-wavelength multi-cell spectrophotometer. A more traditional study of chlorine kinetic isotope effects (KIEs) in the solvolysis of substituted 1-phenylethyl chlorides is reported.” Values of k35/k37 are largely insensitive to the electronic demands of ring substituents and to the polarity of ethanol-water solvent mixtures.The results are either a negation of the Hammond postulate or an indication that a multistep mechanism is operative. The authors favour the latter alternative and propose that a substituent- and solvent-induced variation in the extent of internal ion pair return tends to level the leaving group KIEs. A diminution in k35/k37with CF3CH20H-H20 solvents is evidence for stronger electrophilic solvent participation. While ArCH(CH3)C1 is some 4 x lo5 $me more reattive in solvolysis than ArCH(CF3)Cl (Ar = p-MeOC,H,) the ArCHCH3 and ArCHCF cations are cap- tured equally rapidly by water (k = 5 x lo7s-’ based on equal diffusional rates of capture by N3- see also ref.15).20 This is unexpected in view of the markedly differing stabilities of the cations. Richard argues that the a-CF3 destabilization in the latter is off set by a greater degree of p-Me0 resonance charge delocalization and thus provides a further example of TS imbalance with respect to resonance and 16 C. D. Ritchie and Y. Tang J. Org. Chem 1986,51 3555. 17 M. L. Di Vona G. Doddi G. Ercolani and G. Illuminati J. Am. Chem. SOC.,1986 108 3409. 18 M. R. Edwards P. G. Jones and A. J. Kirby J. Am. Chem. SOC. 1986 108,7067. 19 D. J. McLennan A. R. Stein and B. Dobson Can. J. Chem. 1986 64 1201. *’ J. P. Richard J. Am. Chem. SOC. 1986 108 6819. Reaction Mechanisms -Part (ii) Polar Reactions 51 inductive interactions.In a similar vein Tidwell shows that double destabilization of carbocations by the introduction of two CF groups is markedly attenuated with respect to the large destabilization effected with just one CF, and that in the former case the charge is largely delocalized on to an a-aryl group.21 His studies have been extended to polycyclic 1-arylethyl systems,22 where ion pair pathways are again operative. Maskill has used azoxytosylates to investigate solvolytic intermediates with much success in recent years (equation 2). Heterolytic fragmentation occurs for R = PhCH2 but concurrent nucleophilic attack by the basic nucleophiles OAc- and imidazole occurs at the tosyloxy sulphur atom.23 0- I R-N+=N-OTs + [R+.N,O.OTs-] + [R+OTs-] + N,O .c products A careful study of the rates of reaction of benzyl tosylate in the presence of added solutes in 1 :1 CF3CH20H-H20 reveals the operation of nothing other than &2 reactions for solvent-derived products and those arising from attack by external nu~leophiles.~~" Thus attack on ions or ion pairs is excluded.A parallel study of solvolysis rates in a variety of solvents concurs solvent nucleophilicity is almost as important a determinant of reactivity as is polarity.24b Katritzky's continuing research into the mechanisms of nucleophilic substitutions wherein heterocycles act as leaving groups demonstrates that at the borderline dividing rate-limiting nucleophilic trapping of intimate ion-molecule pairs from formation of free carbocations the pathways are independent.Likewise there is no merging of mechanisms when rate-limiting nucleophilic attack on an ion-molecule pair is contrasted with formation of the pair. The idea of an SN2-intermediate mechanism is not supported by these re~u1t.s.~' The rates of SN1solvolysis of t-alkylpyridinium cations are almost independent of solvent over a wide range of solvent polarity and nucleophilicity.26 The possibility of nucleophilic solvent assist- ance is dismissed as are earlier suggestions that the solvolysis of t-butyl chloride is assisted. In the pH-independent solvolysis of p-methoxystyrene oxide a reversibly-formed intermediate must intervene since the trans-P-deuterio isomer suffers deuterium scrfmbling during rea~tion.~' The intermediate is identified as the zwitterion ArCH-CH2-0-.An unusual cyclization accompanies solvolysis of trimesitylvinyl tosylate (6; Mes = 2,4,6-Me,C,H2). Formation of indene (7) is proposed to result from hydride transfer from a P-mesityl methyl to the cationic centre in the vinyl cation followed by cyclization of the resulting benzylic cation or from electrophilic attack by a methyl C-H bond on a P-mesityl group.28 21 A. D. Allen V. M. Kanagasabapathy and T. T. Tidwell J. Am. Chem. Soc. 1986 108 3470. 22 A. D. Allen R. Girdhar M. P. Jansen J. D. Mayo and T. T. Tidwell J. Org. Chem. 1986 51 1324. 23 H.Maskill J. Chem. Soc. Chem. Commun. 1986 1433. 24 (a) H. Maskill J. Chem. SOC.,Perkin Trans. 2 1986 1241; (b) D. N. Kevill and T. J. Rissrnann J.Chem. Res. (S),1986 252. 25 A. R. Katritzky and B. Brycki Can. J. Chem. 1986 64,1161. 26 A. R. Katritzky and B. Brycki J. Am. Chem. SOC.,1986 108 7295. 27 V. C. Ukachukwu J. J. Blurnenstein and D. L. Whalen J. Am. Chem. Soc. 1986 108 5039. S. E. Biali and 2. Rappoport J. Org. Chem. 1986 51 964. D. J. McLennan Mes\ Mes\ C=C-Mes + /c=c \ /Mes -bMes / Mes OTs Mes Me Mes Non-classical ion matters are hardly new but novel angles continue to be explored. H.C. Brown announces his retirement from the field with two concluding papers of a monumental provocative and stimulating series. In the first the behaviour of U-shaped systems in solvolysis is re-e~amined,~~ and solvent participation in the solvolyses of the non-norbornyl model systems (absent in secondary norbornyl solvolyses) is suggested to account for earlier discrepancies.In the second a direct search for the reputed non-classical stabilization energy is undertaken -the 6-8 kcal mol-' required to explain the exo-endo rate ratio for solvolyses of secondary norbornyl derivatives on the basis of a delocalized intermediate in the ex0 case.3o Solvolytic data (again corrected for solvent participation) are compared with heats of ionization under stable ion conditions and again the stabilization fails to appear. Yet even these papers may not mark Brown's last words on the subject matters may continue to be argued by public corre~pondence.~' Kirmse has summarized experimental and theoretical studies of cations on the C7HT energy surface.For once attention is focused not on the 2-norbornyl cation but on metastable isomers protected from immediate decay by potential barriers.32 These are considered to be bridged. Studies on nucleophilic capture of isotopically labelled 2-bicyclo[2.1. llhexyl cations are consistent with the intermediacy of equili- brating bridged ions.33 These are believed to be more strongly solvated than has been previously thought to be the case for delocalized cations. Last year was reported a new world record for the ex0 :endo rate ratio in solvolysis of a norbornyl system. In contrast exo- and endo-5-brexyl brosylates acetolyse at almost the same rate and produce predominantly inverted acetates.34 Relative to norbornyl exo-solvolysis is retarded whilst endo-solvolysis is enhanced.These findings are also of relevance to the stereochemical preference of 1,2-migrations in carbenes. An earlier report on the bromination of stereospecifically deuteriated cyclopropane concluded that the reaction stereospecificity demanded the intermediacy of a corner- brominated cyclopropane containing a formal pentacoordinate carbon. Battiste and Coxon now show that the observed result specifically excludes such a symmetrical intermediate and interpret the results in terms of both the degenerate HOMOS of cyclopropane interacting with the ele~trophile.~~ 29 H. C. Brown I. Rothberg and J. Chandrasekharan J. Org. Chem. 1985 50 5574. 30 H. C. Brown M.-H. Rei J. Chandrasekharan and V. Somayiji J. Org. Chem. 1985,50 5578.31 H. C. Brown Acc. Chem. Rex 1986 19 34. 32 W. Kirmse Acc. Chem. Rex 1986 19 36. 33 W. Kirmse V. Zellmer and B. Goer J. Am. Chem. SOC.,1986 108 4912. 34 A. Nickon and R. C. Weglein Tetrahedron Lett. 1986 27 2675. 35 M. A. Battiste and J. M. Coxon Tetrahedron Lett. 1986 27 517. Reaction Mechanisms -Part (ii) Polar Reactions 53 3 Other Nucleophilic Substitutions Our interest in the formation of the first C-C bond in the ZSM-5 zeolite-catalysed methanol-to-gasoline process continues. The world's first commercial plant is now operating successfully in New Zealand using natural gas as the feedstock but while the chemical engineering problems have been overcome the economics (in the light of current low prices for Middle East crude oil) are reputed to be disastrous.Olah reinforces his conviction in favour of the oxonium ylide mechanism by paradoxically questioning earlier evidence provided by others in support of it.36 Ethylene was reported last year to arise from treatmyt of Me30+BF4- with weak bases but Olah now concludes that it comes from Me,OEt present as an impurity. A rival mechanism involving singlet methylene insertion into C-H bonds of an oxonium species is not supported by model laboratory studies. However the novel technique of monitor-ing the reaction by in situ FT-IR fails to provide evidence for detectable concentra- tions of Me30+ under catalytic condition^.^^ Instead an Al-0-Me species is detected whose formation correlates with the onset of hydrocarbon formation and which acts as a methylating agent towards alkenes and aromatics.The possibility that it also methylates dimethyl ether to form transient Me30+ cannot be dismissed. As mentioned earlier the detection of radicals or radical-derived products is not a necessary prerequisite for the operation of a single electron-transfer S mechanism. A better criterion is that the substitution rate is comparable with a reliably calculated electron-transfer rate and this is successfully applied to the reactions of sterically hindered alkyl halides and the anion of 1,4-dihydro-4-methoxycarbonyl-1-methyl-~yridine.~' Radical cations are singularly unreactive with nucleophiles in contrast to carbocations and an extremely simple application of CM theory by Pross shows The concept of 'allowed' and 'forbidden' polar reactions is introduced but the categories are based on energetics rather than orbital symmetry as is the case for pericyclic reactions.Substrate and solvent KIEs in SNreactions have been widely studied but entering group KIEs are rare. The k14/k15values for methyl transfer to pyridines in water fall in the range 0.995-0.998 and are virtually independent of the identity of the nucleophile or leaving Preliminary model calculations and comparison with equilibrium isotope effects for pyridine prot~nation~~~ suggest that early TSs with N-..C bond orders in the 0.2-0.3 range are involved. Interestingly interaction of solvent with free amine in the initial state appears to be a prerequisite. Similar results are obtained for the reactions of substituted dimethylanilines with benzylic arene~ulphonates,~' a system in which substrate KIEs have previously been found to be remarkably substituent-sensitive.Jencks continues his search for intermediates for simple secondary substrates solvolysing in solvents of moderate nu~leophilicity.~~ However rates of reaction of 36 G. A. Olah G. K. Surya Prakash R. W. Ellis and J. A. Olah J. Chem. SOC.,Chem. Commun. 1986 9. 37 T. R. Forester S.-T. Wong and R. F. Howe J. Chem. Soc. Chem. Commun. 1986 1611. 38 T. Lund and H. Lund Tetrahedron Lett, 1986 27 95. 39 A. Proos J. Am. Chem. Soc. 1986 108 3537. 40 (a) J. L. Kun M.W. Daniels K. S. Cook and M. M. Nasr J. Phys. Chem. 1986 90,5357; (b) J. L. Kurz J. E. Pantano D.R.Wright and M.M. Nasr ibid. 1986 90,5360. Earlier results on entering nitrogen KIEs (J. Am. Chem. Soc. 1982 104 5823) have been repudiated. 41 T. Ando H. Yamataka and E. Wada Isr. J. Chem. 1985 26 354. 42 P. E. Dietze and W. P. Jencks J. Am. Chem. SOC.,1986 108 4549. 54 D. J. McLennan p-N02C6H4CH2CHXCH3(X = Br I OTs) with solvent fall on the same Swain- Scott correlation line as do rates of reaction with bonaJidesN2 anionic nucleophiles and it is concluded that the solvolyses are also concerted sN2 albeit through a TS possessing carbocation character. Significantly there is a symbiotic effect when both nucleophile and nucleofuge are polarizable (‘soft’) which indicates coupling in a concerted TS. Jencks acknowledges that much of the controversy regarding solvolysis mechanisms is semantic and points out that substitution reactions at carbon will be stepwise if they can be and will be concerted or will show nucleophilic participation when the carbocation has too short a lifetime to exist in the presence of surrounding nucleophiles.In the Reporter’s view these are wise words. However a case of the Sneen mechanism (a rate-limiting attack of a nucleophile on an ion pair formed in a pre-equilibrium) may have been uncovered. As so elegantly demonstrated in the 1930s by Hughes and his collaborators the second- order rate constant for racemization of one enantiomer of an alkyl bromide in the presence of Br- should be exactly twice the second-order rate constant for isotopic exchange between organic and inorganic bromide if a classical sN2 mechanism is operating.Stein and Moffatt indeed find k,,J k, = 2.0 for ArCHBrCH + LiBr in acetone (Ar = Ph p-BrC6H4 p-N02C6H4).43 But for Ar = p-MeC6H4 the rate ratio is 2.36 f0.24 suggesting the presence of an ion pair intermediate sufficiently stable to suffer internal return with racemization. Expecting the Ar = 3,4-Me2C,H3 com- pound to yield an even higher ratio the authors found instead a value of 1.59 * 0.39 and proposed that frontside exchange of Br- with retention in a loose ion pair was conceivable. Although the authors took pains to minimize the effects of concurrent bromide-induced dehydrobromination the fact remains that concurrent elimination followed by back-addition of HBr could complicate the results.It would be interest- ing to establish the racemization-to-exchange ratios in media containing a non- nucleophilic HBr scavenger. The putative intermediacy of free metaphosphate anion in phosphate ester hydro- lysis is a question similar to those raised on behalf of carbocations. Volume of activation results are consistent with an associative mechanism for aqueous hydroly- sis of 2,4-dinitrophenylphosphatedianion.44 The secondary l60/l80KIE for hydro- lysis of glucose-6-phosphate monoester (non-bridging oxygens) is 1.0046 which is consistent with a dissociative mechanism but does not allow distinction between free metaphosphate and the loose sN2 TS advocated in other recent ~tudies.4~ On the other hand phosphoryl transfer from adenosine 5’-diphosphate to ROH in dry MeCN proceeds with racemization at phosphorus.Free metaphosphate intermediacy is one interpretation but it is not possible to rule out preassociative phosphoryl transfer to a~etonitrile.~~ Indeed positional isotope exchange in the ‘*O-labelled diphosphate is consistent with the latter process.47 A salt containing the sulphur analogue of metaphosphate namely PS; has been prepared.48 43 A. R. Stein and E. A. Moffatt Can. J. Chem. 1985,63 3433. 44 F. Ramirez J. Marecek J. Minore S. Srivastava and W. J. le Noble J. Am. Chem. SOC.,1986,108 348. 45 P. M. Weiss W. B. Knight and W. W. Cleland J. Am. Chem. SOC.,1986 108 2761. 46 P. M. Cullis and A. J. Rous J. Am. Chem. SOC.,1986 108 1298. 47 G. Lowe and S. P.Tuck J. Am. Chem. SOC.,1986 108 1300. 48 H. W. Roesky R. Ahlrichs and S. Brode Angew. Chem. Int. Ed. Engl. 1986 25 82. Reaction Mechanisms -Part (ii) Polar Reactions 55 Heavy-atom KIEs are usually (and tediously) measured by competitive methods. The methanolysis of p-nitrostyrene oxide under basic and acidic conditions has been examined by direct kinetics as far as ring l80and 13C KIEs are concerned. Base-catalysed methanolysis occurs primarily at the unhindered carbon and yields KIEs consistent with SN2 ring-opening by OMe-. In contrast acid-catalysed methanolysis results in attachment of the nucleophile to the benzylic carbon of the 0-protonated epoxide. A high value of k16/kl* is indicative of a well-broken C.s.0 bond in the TS but the less than maximal a-k,/k value supports concurrent nucleophilic participation by MeOH rather than a free carbocationic intermediate.49 4 Elimination Reactions Studies of conventional eliminations from halides and 'onium salts are decreasing at such a rate that this area can hardly be regarded any longer as the mainstream of elimination chemistry.Nevertheless two such papers justify citation. Discovery and exploration of the anti-syn dichotomy have given rise to concern about the earlier interpretation of results pertaining to influences on orientation etc. The 2-phenylethyl system has been a mechanistic template in this regard and the reaction of stereospecifically deuteriated PhCHDCHDNMeT with OEt-EtOH has been confirmed as wholly anti. The oxide of the corresponding amine eliminates exclus- ively by a syn path~ay.~' There are strong suggestions that the p-nitro analogue of the ammonium ion eliminates by an ElcB pathway but the stereochemical con- sequences could not be examined since the deuteriated p-nitrostyrene suffers label scrambling under the conditions employed for elimination.Unimolecular (E 1) reactions of 'onium salts are rare in view of the diminished nucleofugality of say the NMe; group. It is thus doubly surprising to find that 9-benzylfluoren-9- yltrimethylammonium ions undergo E 1 eliminations since the carbocation is anti- aromatic. Nevertheless the reaction clearly occurs in this way and ring substituent effects substantiate the claim that initial state steric repulsions aid expulsion of the bulky nucleof~ge.~~ The elimination of FINO2 from ArCH2C(N02)MeR (Ar = p-NO&H4; R = Me or But) appears to be a polar concerted E2 reaction in OMe-MeOH-Me2S0.52 The nucleofugality order Br- > NO > C1-is established.At a time when polar mechanisms are being increasingly re-assigned as radical ion pathways it is a pleasure to find such a strong electron acceptor acting in a polar fashion. Imine-forming eliminations equation 3 are generally E2,like their less facile alkene-forming counterparts. An investigation of ArCH2N(X)Me+ R2NH -+ ArCH=NMe + R,kHX-(3) responses to substituent base nucleofuge and isotopic variation shows however that the TS is symmetrical rather than carbanionic or carbocationic in ~haracter.~~ A rare example of the Melander-Westheimer k,/k maximum is found for a base strength variation covering only 2 pK units.49 S. P. Jacober and R. P. Hanzlik J. Am. Chem. SOC.,1986 108 1594. 50 B. R. Dohner and W. H. Saunders Can.J. Chem. 1986 64 1026. 51 P. J. Smith and J. Pradhan Can.J. Chem. 1986 64 1060. 52 R. K. Noms and T. A. Wright Aust. 1 Chem. 1986 39 281. 53 B. R. Cho S. K. Namgoong and R. A. Bartsch J. Org. Chem. 1986 51 1320. 56 D. J. McLennan On the other hand eliminations from isonitriles CN-CH2CH2-Z by OEtC-EtOH are ElcB in cases where loss of CNH competes with removal of HP4 While isonitrile is not a highly ranked nucleofuge it is at least 10" better than cyanide. The E 1cB mechanism of ester hydrolysis is now well-established.Another mechanistic criterion is available since volumes of activation are markedly different from those for the more usual BA,2 me~hanism.~~ Mechanistic variation within the ElcB spectrum from (ElcB) to can be brought about by introduction of a bulky substituent in the acyl moiety.56 The existence of a neutral sulphonylamine intermediate in the alkaline hydrolysis of aryl sulphamate esters has been established. The pH-rate profile however requires another intermediate and the unprecedented involvement of a dianion (Scheme 1) is ~uggested.~' -2-H2NS02-OAr HNSO,-OAr Y NSO2-0Ar I-... HN=S02 \p~oductsj=102 Scheme 1 The full paper on the enormous stereoelectronic effect of the nitrogen lone pair in promoting chloride loss from the anions of (E)-and (2)-benzohydroxyimoyl chlorides has appeared.58 This effect is not universally accepted as far as lone pairs on neighbouring oxygens are concerned but the results here assert a clear antiperi- planar preference for a single lone pair on nitrogen.5 Addition Reactions The +first direct measurement of rate constants for addition of carbocations (Ar,CHBCl in CH2C12 at -20 to -9OOC) to alkenes has been rep~rted.'~ The reactions are second-order and ion association effects are negligible. The results should be of assistance in understanding the initial step(s) in cationic alkene polymerization. An investigation of the bromination of 3-substituted cyclohexenes by Br and Br in CH2CI2 and CHC13 substantiates the mechanistic proposals reported last year.60 Charge transfer complexes are essential intermediates but different mechanisms operate for the two reagents and this is reflected in markedly different diaxial :diequatorial product ratios.61 In particular Bu4NBr3 is a most suitable reagent for stereoselective anti-diaxial addition irrespective of the 3-substituent.54 B. A. Jones M. Varma and C. J. M. Stirling J. Am. Chem. SOC.,1986 108 3153. 55 N. S. Isaacs and T. S. Najem Can. J. Chem. 1986 64 1140. 56 M. Inoue and T. C. Bruice J. Org. Chem. 1986 51,959. 57 S. Thea G. Cevasco G. Guanti and A. Williams J. Chem. SOC. Chem. Commun. 1986 1582. 58 A. F. Hegarty and M. Mullane J. Chem. SOC. Perkin Trans. 2 1986 995. 59 R. Schneider U. Grabis and H. Mayr Angew. Chem. Int. Ed. Engl.1986 25 89. 6o D. J. McLennan Annu. Rep. bog Chem. Sect. B Org. Chem. 1985 82 67. Note in ref. 66a read J. Org. Chem. for J. Am. Chem. Soc. and in ref. 666 read J. Am. Chem. SOC.,1985 108 2464. 61 G. Bellucci R. Biachini and S. Vecchiani J. Org. Chem. 1986 51 4224. Reaction Mechanisms -Part (ii) Polar Reactions Electrophilic bromination of micelle-associated alkenes (fatty acids esters and alcohols) has been used to probe micellar structure and action.62 A segment pro- trusion model is used to account for exclusively anti-addition and rates slower than those in aqueous solution. A bromonium ion intermediate is believed to be formed and trapped in a polar region of the micelle and it is proposed that the double bond initially enters this reactive region by protrusion of a chain segment from a non-polar region.The small probability of this is offset by the high rate of reaction with bromine once the protrusion occurs. Unexpected participation by sulphone groups during alkene bromination has been reported. Bromination of (8) yields a substantial proportion of cis-dibromide and a long-range Coulomb interaction between sulphonyl oxygen and an open carbocationic centre is ~uggested.~~" Even nucleophilic interaction is possible bromi- nation of (9) in CH2C12 yields a product thought to be ( Clearly the inherently low nucleophilicity of sulphone oxygen is offset by proximity to the reaction site in (9). 6 Aromatic Substitution and Rearrangements Genuinely electrophilic processes are hard to find this year.The reactivity of electrophiles does not seem to be as seriously attenuated by solvent as is the case for nucleophiles. Gaseous t-butyl cation shows normal temperature-dependent intermolecular (benzene us. toluene) and intramolecular positional selectivity (within toluene).64 Thus these ion-molecule reactions are essentially thermal processes at the high pressure limit. 2-Nitro- rn-xylene and some nitrophenols undergo a first-order 1,3-nitro-group rearrangement in CF3S03H at 100 "C,giving the lie to the idea that nitration products are universally formed under kinetic control.65 Mechanistic details are as yet unclear but reversible protonation to yield a Wheland intermediate seems likely. Direct evidence for a nitro-nitrito rearrangement following ips0 nitration of a phenol has been presented.& The nitrite is unstable and loses oxides of nitrogen in the presence of water.A similar suggestion made late last year but based on indirect evidence6' has apparently been confirmed. A homolytic mechanism has been tentatively pro- posed. 62 R. B. Lennox and R. A. McClelland J. Am. Chern. SOC.,1986 108 3771. 63 (a) J. I. G. Cadogen D. K. Cameron I. Gosney R. M. Highcock and S. F. Newlands J. Chem. SOC. Chem. Commun. 1985 1751; (b) ibid. 1986 766. 64 F. Cacace and G. Ciranni J. Am. Chem Soc. 1986 108 887. 65 P. Barrow J. V. Bullen A. Dent T. Murphy J. H. Ridd and 0.Sabek J. Chem. SOC.,Chem. Commun. 1986 1649. 66 M. R. Amin L. Dekker D. B. Hibbert J. H. Ridd and J. P. B. Sandall J.Chem. SOC.,Chem. Commun. 1986 658. 67 M. P. Hartshorn R. J. Martyn W. T. Robinson K. H. Sutton J. Vaughan and J. M. White Aust. J. Chem. 1985 3,1613. 58 D. J. McLennan Electrophilic mechanisms for the HN02-catalysed nitration of p-nitrophenol by aqueous HN03 are abandoned in favour of an electron-transfer radical process in the light of new evidence presented by Ali and Ridd.68 The proposal is that p-nitrophenoxide ion is oxidized by NO+ to the radical which then couples with nitrogen dioxide itself generated by reduction of NO;. However the mechanism( s) of nitration of some methylnaphthalenes under various conditions do not involve coupling between the free arene-radical cation and NO2 formed in a SET step.69 Both the electron transfer and proton transfer aspects of the Marcus equation are used in analysing the energetics of electron transfer from methylarenes to Fe"' complexes and consequent proton loss from the resulting radical cations.70 On the nucleophilic substitution side a surprise comes with a report of proton sponge [1,8-bis(dirnethylamino)naphthalene]acting as a carbon n~cleophile.~~ With strongly electrophilic substrates such as 4,6-dinitrobenzofuroxan proton sponge reacts through C-4 of the naphthalene ring to form zwitterionic adducts which at least preserves the reputation of the amino nitrogens as centres of low nucleophilicity towards anything but protons.7 Carbanions and Proton Transfer Kinetic and KIE anomalies in proton transfer reactions involving carbon acids have often been attributed to the intermediacy of hydrogen-bonded carbanions capable of suffering internal return without exchange.Direct evidence ('H n.m.r. and i.r.) has now been presented to substantiate the existence of such species.72 The spectra of suitable hydroxy-substituted fluorenide and indenide anions can be interpreted in terms of intramolecular c..-HO bonds. The synthetic utility of 1,3-dithiane anion as an acyl anion equivalent will be most marked if it is generated under ion-pairing conditions rather than in Me2S0 as solvent.73 This does not apply however to carbanions with highly delocalized charge. The aqueous pK of toluene is of interest in anchoring carbon acid acidity scales and in comparing scales derived from various basic media.The latest estimate based on isotope exchange measurements and the rate constant for reaction of benzyl anion with water (albeit in THF media) is 39.6 per hydrogen.73 The acetylide anion is apparently not stabilized by resonance.74 The role of base solvation and solvent reorientation in proton transfer has been examined in terms of the principle of imperfect synchr~nization.~~ Intrinsic rate constants for deprotonation of 1,3-indandione by carboxylate ions increase as the Me2S0 content of Me2SO-H20 solvent mixtures increases and this can be inter- preted in terms of desolvation occurring ahead of proton transfer with enolate ion solvation lagging far behind.75" On the other hand the intrinsic rate constants for deprotonation of 9-cyanofluorene by amine bases are independent of Me2S0 content.75 6a M.Ali and J. H.Ridd J. Chem. SOC.,Perkin Trans. 2 1986 327. 69 L. Eberson and F. Radner Acta Chem. Scond. Ser. B 1986 40 71. 70 C. J. Schlesener C. Amatore and J. K. Kochi J. Phys. Chem. 1986 90 3747. 71 F. Terrier J.-C. Halle M.-J. Pouet and M.-P. Simonnen J. Org. Chem. 1986 51 409. 72 P. Ahlberg B. Johnson I. McEwan and M. Ronnqvist J. Chem. SOC.,Chem. Commun. 1986 1500. 73 A. Streitwieser and J. X.Ni Tetrahedron Lett. 1985 26 6317. 74 A. J. Kresge and M. F. Powell J. Org. Chem. 1986 51 819. 75 (a) C. F. Bernasconi and P. Paschalis J. Am. Chem. SOC.,1986 108 2969; (6) C. F. Bernasconi and F. Terrier Can. J. Chem. 1986,64 1273. Reaction Mechanisms -Part (ii) Polar Reactions 59 A full account of Stirling's remarkable findings on cyclization of stabilized car- banions has appeared.76 Cyclopropane rings are the most readily formed by several orders of magnitude despite their inherently greater strain and this enhanced reactivity has an entropic rather than an enthalpic origin.These results are consistent with TS structures wherein the nucleofuge is well on its way out with ring formation lagging well behind. A model for prediction of diastereoselectivity in reactions of prochiral carbanions (or their equivalent) with prochiral ketones in the absence of chelation control has hitherto been lacking. This deficiency is now remedied by an empirical model based on a Burgi-Dunitz trajectory and the assumption of an early TS structure (steric approach 8 Carbonyl Derivatives and Tetrahedral Intermediates A landmark study on the mechanism and stereochemistry of the Wittig reaction has been published in full.Direct observation of diastereomeric 1,2-0xaphosphetanes by low-temperature n.m.r. allows rationalization of 'stereochemical drift' in that correspondence between the proportions of cis- and trans-intermediates prior to alkene formation and the final proportion of (E)-to (2)-alkene is lacking.78 Selective reversibility of oxaphosphetane formation appears to be responsible and in light of this evidence for an element of thermodynamic control it is not possible to define the stereochemistry of the Wittig reaction in terms of alkene products alone. Unfortunately the reactions of stabilized phosphorus ylides were not amenable to n.m.r.observation. The authors are candid in conceding that many important details remain unclear. Not so elusive are details on the hydroxide-promoted chlorination of acetone. A complete kinetic analysis involving the evaluation or estimation of 27 rate and 16 equilibrium constants describing the formation of 25 unstable or metastable inter- mediates and products has been described.79 The situation is therefore somewhat more complex than that presented in organic textbooks and the principal product is lactate rather than chloroform plus acetate. The former appears to arise from a complex pair of pathways involving hydration of mono- and dichloro-acetone. More quantitative work on enols and enolates has appeared.The equilibrium constant for the phenol 2,4-cyclohexadienone equilibrium is around lo-" at 80 0C.80The acidity constant for isobutyraldehyde enol and the keto-enol equilibrium constant have been evaluated,81' and a Marcus equation analysis of the acid- catalysed ketonization of both the enolate and enol has been performed.81b In the latter study the RSP holds in that the Bronsted a is significantly lower for the more reactive enolate. Unexpected catalysis by HSO in aqueous H,SO solutions used in earlier work has forced revision of figures for the enolization of acetophenone 76 F. Benedetti and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1986 605. 77 A. R. Bassindale R. J. Ellis J. C.-Y. Lau and P. G. Taylor J. Chem. SOC.,Chem.Commun. 1986 98. 78 B. E. Maryanoff A. B. Reitz M. S. Mutter R. R. Inners H. R. Almond R. R. Whittle and R. A. Olofson J. Am. Chem. SOC.,1986 108 1664. 79 J. P. Guthrie and J. Cossar Can. J. Chem. 1986,64 1250. 80 M. Capponi I. Gut and J. Win Angew. Chem. Int. Ed. Engl. 1986 25 344. 81 (a) Y. Chiang A. J. Kresge and P. A. Walsh J. Am. Chem. SOC.,1986 108 6314; (b) P. Pruszyniski Y. Chiang A. J. Kresge N. P. Schapp and P. A. Walsh J. Phys. Chem. 1986 90,3760. 60 D. J. McLennan (pKE = 7.96) and for its ionization as a carbon acid (pK = 18.31)in dilute aqueous solution.82 Last year it was shown that base-catalysed ring-opening of a cyclic hemiacetal having a phenolate leaving group occurs by a stepwise mechanism. When an even more stable carboxylate leaving group is involved as with the conversion of 3-hydroxyphthalide into p-formylbenzoic acid a concerted mechanism is enforced by the instability of the conjugate base of the substrate relative to the product,83 to the point where the existence of the conjugate base (the tetrahedral intermediate in attack of H-on phthalic anhydride) is doubtful.The acid-catalysed hydrolyses of acetals and thioacetals of p-Me2NC6H4CH0 have been investigated in detail for the opposite reason the oxocarbocationic intermediate should be so stable that a diversity of rate-limiting steps should be observed. This has been realized. Depending on the pH and the functionality undergoing hydrolysis general acid-catalysed breakdown of protonated acetal to the oxocarbocation or attack of water on this stabilized intermediate can be detected as the rate-limiting step.84 But in no case is hemiacetal breakdown rate-limiting.The remarkable bond length-reactivity correlation earlier observed with respect to leaving group variation in R-OX compounds has now been successfully extended to hydrolysis of acetals (R = R'O-CHR') in which R is varied.85 Thus the more stable is the cation R+ the longer is the R-OX bond and the more reactive is the compound. Lengthening a bond in a crystal correlates with the ease of breaking it heterolytically in solution. The stereochemistry of reaction of ester enolates bearing a P-oxygen with elec- trophiles,86" and of alkylation of 2-t-butyl-5-X-1,3-dioxanes (X = EWG)86bhave been rationalized in terms of stereoelectronic control (or rather control by antiperi- planar lone pairs).But the theory of such stereoelectronic effects has come under close scrutiny. Bennet and Sinnott have described a monumental KIE study of the acid-catalysed hydrolyses of methyl a-and P-glucopyranosides (seven isotopic positions with 3 primary and 4 ~econdary).~' The rate-limiting step is unimolecular scission of the (protonated) exocyclic C-0 bond. Primary KIEs allow evaluation of the extent of bond-breaking and nucleophilic assistance by the endocyclic oxygen. The known conformational dependence of some of the secondary KIEs then allows several TS bond angles to be estimated and the remainder of the TS structure has been deduced by molecular mechanics calculations.The minimum energy structures obtained flatly contradict the antiperiplanar lone pair hypothesis which in any case is not expected to apply to systems reacting through late TSs. Four years ago Perrin provided evidence in support of the theory based on the regioselectivity of hydrolysis of cyclic amidines. He now concedes that the system studied was biased as far as differential leaving group abilities were concerned and has now reinvestigated the situation with a less biased substrate.88 The conclusion which applies to the forma- 82 J. R. Keefe A. J. Kresge and T. Toullec Can. J. Chem. 1986 64 1224. 83 R. A. McClelland and P. E. Sgrensen Can. J. Chem. 1986 64 1196. 84 T. H. Fife and R. Natarajan J. Am. Chem. SOC.,1986 108 2425. 85 P.G. Jones and A. J. Kirby J. Chem. SOC.,Chem. Commun. 1986 444. 86 (a) M. Caron T. Kawamata L. Ruest P. Soucy and P. Deslongchamps Can. J. Chem. 1986,64 1781; (b) A. Ndibwami and P. Deslongchamps ibid. 1986 64 1788. 87 A. J. Bennet and M. L. Sinnott J. Am. Chem. SOC.,1986 108 7287. 88 C. L. Perrin and 0. Nufiez J. Am. Chem. SOC.,1986 108 5997. Reaction Mechanisms -Part (ii) Polar Reactions 61 tion of the tetrahedral intermediate is that the stereoelectronic hypothesis is barely consequential in the case of 6-membered cyclic amidinium ions and of no import as far as the 5-and 7-membered analogues are concerned. 9 Some Probes of Polar Mechanisms In claiming last year that their linear solvation energy relationship was so widely applicable as to approach the status of a law of nature Kamlet and Taft challenged those wedded to a system-specific statistical approach.The chemometricians of UmeH have responded in kind but alas no reconciliation of views is yet apparent. The latter reinforce their arguments that within the framework of any statistical model lies a distinction between goodness of fit and predictive power and that such models must of necessity be local rather than universal.*’ The diversity of views expressed in other work to be cited in this section would tend to bear this out. The a-effect on nucleophile reactivity has been critically scrutinized by Hoz and Buncel who conclude that none of the theories proposed so far accounts for all of the facts.” An unusual solvent effect on the a-effect’” and a rationalization in terms of initial state destabilization by lone-pair repulsion” are testimony to the fact that much remains to be understood.Last year it was proposed that the a-effect had a thermodynamic rather than a kinetic origin. Experimental evidence is now available -a-eff ect nucleophiles exhibit enhanced equilibrium constants but normal rate constants for addition to benzylidene Meldrum’s acid.’* Lewis has reviewed his work on methyl transfer reaction^'^ and shows that although the Marcus equation (a quantitative expression of the RSP) is applicable selectivities are almost constant. The general Marcus relationship is compatible with linear free energies over wide rate ranges. The need for a loose VB contribution X-Me+Y-to the TS hybrid is emphasized which concurs with conclusions from methyl transfers to water.94 Here little O..C bonding has occurred at the TS as a result of solvational and bonding coordinates being only partially coupled.Methyl transfer data for equilibrium cases where arenesulphonates are the mobile groups are used as a basis to set up Bronsted plots for leaving group departure. The slopes are as would be intuitively e~pected.’~ Nevertheless it has been evident for a number of years that all is not well as far as using a Bronsted a or p as an index of the degree of bonding in a TS or as a selectivity parameter in an RSP context is concerned. Jencks and co-workers report a case where increasing basicity of amines results in decreasing reactivity in phosphoryl tran~fer.’~ In the terminology of Bernasconi partial desolvation of the stronger bases runs ahead of proton transfer at the TS (imperfect synchr~nization).’~ Over-89 s.Wold and M. Sjostrom Acfa Chem. Scand. Ser. B 1986 40,270. 90 S. Hoz and E. Buncel Isr. J. Chem. 1985 26 313. 91 (a) E. Buqcel and I.-H. Um J. Chem. SOC.,Chem. Commun. 1986 595; (b)S. Oae and Y. Kadoma Can. J. Chem. 1986 64,1185. 92 C. F. Bernasconi and C. J. Murray J. Am. Chem. SOC.,1986 108 5251 93 E. S. Lewis T. A. Douglas and M. L. McLaughlin Isr. J. Chem. 1985 26 331; E. S. Lewis J. Phys. Chem. 1986,90 3756. 94 J. L. Kurz and L. C.Kurz Zsr. J. Chem. 1985 26 339. 95 R. V. Hoffman and J. M. Shankweiler J. Am. Chem. Soc. 1986 108 5536.96 W. P. Jencks M. T. Haber D. Herschlang and K. L. Nazarentian J. Am. Chem. SOC.,1986 108,479. 97 C. F. Bernasconi and R.D. Bunnell Zsr. J. Chem. 1985 26 420. 62 D. J. McLennan whelming solvation sensitivity is held responsible. Bordwell has been concerned for some time that results of his extensive studies involving reactions of carbon elec- trophiles do not accord with the RSP (or with the Bema Hapothle model -see last year p. 73).98 A detailed study of the response (or lack of it) of PNuand PLGto substituent vfriation elsewhere in the system comprising fluorenide anions reacting with ArCH2NMe2Ar' substrates in Me2S0 is reported. In only a few cases do the experimental results accord either with this theory or with the Pross-Shaik CM Having conceded that the RSP may well be valid in cases where a low activation barrier accompanies a true single-step reaction,97 Bordwell now dissects an sN2 reaction in solution into ion-dipole complex formation followed by bond- making and -breaking in an activated process.Such complexes respectable in gas-phase SN2reactions should survive in polar aprotic solvents. Parameters such as PNureflect charge transfer in complex formation whilst PLGis manifested in the second step and is independent of the basicity of the nucleophile. The central carbon p value presumably reflects variation in balance between complex formation and destruction giving rise to the familiar U-shaped Hammett plots in benzylic systems. In terms of the CM model the explanation is that in systems such as benzyl where intermediate configurations are of importance at higher energy levels but not in reactants or products p and p values are not valid indices of TS bonding.'.''' Given that charge transfer is an essential component of the CM model the similarities between the two explanations are more important than the differences.A search for charge-transfer complexes in SNArreactions involving carbanionic nucleophiles in Me2S0 was even though PNuis larger here than in sN2 processes. Imperfect synchronization or the importance of intermediate configurations yields a Bronsted a of infinity [p(rate) = 0.27; p(equi1ibrium) = 01 for the reactions of j3-nitrostyrenes with amines.'02 Anomalies associated with nitro -* nitronate conversions are thus not confined to the deprotonation of nitroalkanes.The principle of imperfect synchronization also explains why the addition of amines to benzylidene acetylacetone has an abnormally high intrinsic barrier.lo3 Steric inhibition of reson- ance in the TS leading to the adduct appears to run ahead of C-.N bond formation to the extent that extended n-overlap is absent in the substrate itself as evidenced by a crystallographic determination. Other work on reactivity and selectivity s~pports''~ or denieslo5 the reality of the RSP. Together with the work cited in the preceding paragraphs this suggests that the RSP area is chaotic. Perhaps as suggested by an anonymous referee to the Israel Journal of Chemistry issue devoted to the problem it would be best to talk about reactivity-selectivity efects rather than a principle.An effect is permitted to be distinguished by its absence. Isotopic selectivity (i.e.KIEs) should be more well-behaved and less controversial. However the TS for hydride transfer remains in doubt in that there is yet no.genera1 98 F. G. Bordwell J. C. Branca and T. A. Cripe Isr. J. Chem. 1985 26,357. 99 F. G.Bordwell and D. L. Hughes J. Am. Chem. Soc. 1986 108 7300. 100 A. Pross Zsr. J. Chem. 1985 26 390. 101 F. G.Bordwell and D. L. Hughes J. Am. Chem. Soc. 1986 108 5991. 102 C. F. Bernasconi R. A. Renfrow and P. R. Tia J. Am. Chem. SOC.,1986 108 4541. 103 C. F. Bernasconi and A. Kanavariotti J. Am. Chem. Soc. 1986 108 7744. 104 D. J. Hupe and E. R.Pohl lsr. J. Chem. 1985 26,395; M.-F. Ruasse ibid. 1985 26,414. 105 N.C.J. Chokotho and C. D. Johnson Isr. J. Chem. 1985 26,409. Reaction Mechanisms -Par? (ii) Polar Reactions agreement as to whether the donor-..H--acceptor TS is linear or bent. Studies on transfer promoted by NAD( P)H models suggest a bent TS,lo6 on the grounds that isotope effects are temperature-independent in an intramolecular case in accordance with the Kwart hypothesis. But Kwart's suggestion has no theoretical foundation and an alternative practical proposal concerning the observance of apparently temperature-independent isotope effects has been made.'" Calculations at the ab initio level demonstrate a linear TS for hydride transfer between CH3NH2 and CH2NHl,108nand while tunnelling contributions are non-negligible neither are they of great importance.'0sb The tendency of genuine hydride transfers to mimic behaviour expected of SET processes is analysed in terms of the CM model.'06 Full details of the scope and precision of the measurement of kinetic deuterium isotope effects by natural abundance deuterium n.m.r.are now a~ailable.'~' The method obviates the need to synthesize specifically deuteriated substrates although gram quantities of material may be required. Even small secondary effects can be observed provided that primary KIEs are absent. 106 J. W. Verhoeven W. van Gerresheim F. M. Martens and S. M. van der Kerk Tetrahedron 1986,42,975. 107 D. J. McLennan and P. M. W. Gill Zsr. J. Chem. 1985 26 378. 108 (a) B.G. Hutley A. E. Mountain I. H. Williams G. M. Maggiora and R. L. Schowen J. Chem. SOC. Chem. Commun. 1986 267; (b) 1303. 109 R. A. Pascal M. W. Baum C. K. Wagner L. R. Rodgers and D.-S. Huang J. Am. Chem. Soc. 1986 108;6477.