4 Reaction Mechanisms Part (ii) Polar Reactions By D. J. McLENNAN Department of Chemistry University of Auckland Auckland New Zealand 1 Introduction Some journals take some time to arrive in the Southern Hemisphere thus the 1984 literature has not been completely covered. The deficiency will be made up in next year's Report. A new section in this Report deals with free energy relationships isotope effects etc. as they pertain to the study of polar mechanisms. Indeed a monograph on methods of determining reaction mechanism has appeared.' Two deservedly popular texts have been produced in second edition guise.293 A mono-graph on the neutral reactive intermediates in organic chemistry discusses ionic routes to some of the intermediate^.^ Russian authors have reviewed non-classical carbocations' and rearrangements of carbocations by 1,2-shifts6 in exhaustive detail.Simonetta has reviewed his work on the theoretical calculation of reaction paths in SN2 and other proce~ses.~ An iconoclastic paper by Shaik and Bar questions the importance of rr-resonance stabilization in organic chemistry and suggests that the delocalized rr-systems of the ally1 anion (and radical) may well be unstable or metastable electronic species which have geometric symmetry conferred on them by the a-skeleton.' In a dmilar vein Dewar argues that multibond reactions (except for E2 and S,2') cannot normally be synchr~nous,~ and reviews the evidence. A review on the use of pyridines as leaving groups in SNreactions emphasizes the mechanistic diversity of these processes." Kirby has reviewed stereoelectronic effects on acetal hydrolysis with particular reference to lysozyme binding and catalysis." Among other things he draws attention to the hitherto unacknowledged insight possessed by Samuel Taylor Coleridge (1772-1834) on the subject of enzymatic catalysis.The reactivity of pure B. K. Carpenter 'Determination of Organic Reaction Mechanisms' Wiley New York 1984. * F. A. Carey and R. J. Sundberg 'Advanced Organic Chemistry-Part A Structure and Mechanisms' 2nd edn. Plenum New York 1984. R. A. Y. Jones 'Physical and Mechanistic Organic Chemistry' 2nd edn. Cambridge University Press 1984. C. Wentrup 'Reactive Molecules' Wiley New York 1984. V. A. Barkhash Topics Cum Chem.. 1984.116/117. 1. V. G. Shubin Topics Cum.Chem. 1984 116/117 267. ' M. Simonetta Chem. SOC.Rev. 1984 14 1. S. S. Shaik and R. Bar Nouv. J. Chim. 1984 8 411. M. J. S. Dewar J. Am. Chem. Soc. 1984 106 209. A. R. Katritzky and G. Musumarra Chem. SOC.Rev. 1984 14 47; A. R. Katritzky and C. M. Marson Angew. Chem. Int. Ed. Engl. 1984 23 420. I' A. J. Kirby Acc. Chem. Res. 1984 17 305. 47 D. J. McLennan conformational isomers has been reviewed,12 and the application of linear free- energy relationships (LFERs) to the related Curtin-Hammett principle has been disc~ssed.'~ The evidence afforded by primary kinetic isotope effects (KIEs) to the investigation of internal return processes dominates a review on carbanion formation and proton transfer^,'^" whilst acidity and structural factors are featured in an account of work on carbanion ion pairs and tri~1ets.l~' A review of intramolecularly H-bonded acids has a~peared.'~ Page has reviewed work on the mechanisms of reactions of p-lactam antibiotics.16 Co-operative effects between substrate binding and rate enhancements dominate a discussion on models for enzymatic catalysis." Polar and electron-transfer (ET) mechanisms are important in copper-assisted nucleophilic substitution of halide ion in aryl halides.18 The conventional wisdom is that if one wishes to study the properties of reactive ionic intermediates one stabilizes them; Tidwell demonstrates that as much if not more insight into carboca- tions can be afforded by de~tabilization.'~" A review on the homotropylium cation concludes that it is homoaromatically ~tabilized.'~' The evidence for Hg" and Pd" catalysis of hetero-Cope rearrangements proceeding via electrophilic cyclization (1) +(2) +(3) has been reviewed.Cope rearrange- ments of acyclic 1,Sdienes catalysed by PdC12 are believed to proceed by the same E route.20 Enantioselection in reductive addition of nucleophiles to carbonyl groups has been reviewed for cases where chelation control can be adjustedz1 and where microbial enzymes are involved.22 2 Solvolysis and Carbocations It is not generally appreciated that carbocationic intermediates can be involved in the photolytic decomposition of alkyl halides. Kroppz3 has reviewed the evidence for products arising from both homolytic and heterolytic pathways and the 12 M.Oki Acc. Chem. Res. 1984 17 154. l3 C. L. Perrin and J. I. Seeman J. Org. Chem. 1984,49 2887. l4 (a) H.F. Koch Acc Chem. Res. 1984 17 137; (b) A. Streitwieser ibid. 353. F. Hibbert Acc. Chem. Res. 1984 17 115. 16 M. I. Page Acc. Chem. Res. 1984 17 144. 17 J. Rebek Acc. Chem. Res. 1984 17 258. 18 J. Lindley Tetrahedron 1984 40,1433. 19 (a) T. T. Tidwell Angew. Chem. Int. Ed. Engl. 1984 23,20; (b)R. F. Childs Acc. Chem. Res. 1984 17 347. 20 L. E. Overman Angew. Chem. Int. Ed. Engl. 1984 23 579. 21 M.T.Reetz Angew. Chem. Znt. Ed. Engl. 1984 23 556. 22 C. J. Sih and C.-S. Chen Angew. Chem. Int. Ed. Engl. 1984 23 570. 23 P. J. Kropp Acc. Chem. Res. 1984 17 131. Reaction Mechanisms -Part (ii) Polar Reactions 49 dichotomy has been exemplified in the photosolvolyses of ArCH2X compounds (Ar = naphthyl; X = C1 Br I).24 The room-temperature photolytic decomposition of triarylvinyl halides in solution25 yields a spread of products similar to that obtained from thermal solvolysis at higher temperatures,26 thus implicating vinyl cations in the photolytic process.N.m.r. techniques have been used to demonstrate the angular dependence of hyperconjugative stabilization of bicyclo[2.2.2]0cty1~~~**and bicycl0[2.2.l]heptyl~~ cations. Hyperconjugation vanishes when the C -H bond axis is orthogonal to the axis of the empty p-orbital confirming the point elegantly made by Shiner some 25 years ago. Olah has succeeded in generating the first a-nitrodiaryl methyl cations from Ar2C(N02)2 in FS03H/S02C1F.29 No such cation is however obtained from 9,9-dinitrofluorene which is not surprising since the parent 9-fluorenyl cation has yet to be observed under stable ion conditions.The behaviour of 1-phenethyl derivatives has been a cornerstone of solvolysis theories for some 50 years yet Jencks and co-workers have found good reasons for furthering these studies on the SN1-&2 borderline. The lifetimes of intermediates resulting from solvolyses of activated 1 -phenethyl derivatives have been estimated?' Capture of 1-phenethyl cations by alcohols shows a surprisingly large Pnuclof 0.5 the selectivity of the cations is inversely proportional to their rea~tivity,~~" and general base catalysis of nucleophilic attack is required for alcohol addition to the more stable cation^.^' The nature of the bimolecular substitutions with less activated derivatives has been probed and it is concluded that these are concerted sN2 processes proceeding through 'exploded' transition-states that have carbocationic character.32 Virtually the whole spectrum of solvolytic behaviour is exhibited by the solvolyses of secondary (4) and tertiary (5) a-keto mesylates and triflate~.~~ a-Keto carbocations and ion pairs are strongly implicated and it is suggested that destabilizing inductive electron-withdrawal by the a-C=O is at least balanced by resonance stabilization OY OY I I MeCHCOR MeCCOR Y = Ms or Tf I Me (4) (5) 24 G.H. Slocum and G.B. Schuster J. Org. Chem. 1984 49 2177. 25 T. Kitamura S. Kobayashi H. Taniguchi C. Y. Fiakpui C. C. Lee and Z. Rappoport J. Org. Chem. 1984,49 3167. 26 Z. Rappoport C. Y. Fiakpui X.-D. Lu and C. C. Lee J. Org. Chem. 1984,49,470; D. Wanigasekera C. C. Lee Y. Houminer M. Aviv and Z. Rappoport ibid.,4367. H.-U. 27 Siehl and H. Walter J. Am. Chem. Soc. 1984 106 5355. 28 D. A. Forsyth J. H. Botkin and V. M. Osterman J. Am. Chem. SOC,1984 106 7663. 29 G. A. Olah G. K. Surya Prakash M. Arvanaghi V. V. Krishnamurthy and S. C. Narang J. Am. Chem. SOC.,1984 106 2378. 30 J. P. Richard M. E. Rothenberg and W. P. Jencks J. Am. Chem. SOC.,1984 106 1361. 31 (a) J. P. Richard and W. P. Jencks J. Am. Chem. SOC.,1984 106 1373; (b) 1396. 32 J.P. Richard and W. P. Jencks J. Am. Chem Soc. 1984 106 1383. 33 X. Creary J. Am. Chem. SOC., 1984 106 5568. D. J. McLennan (equation 1). Accurate MO calculations confirm this view.34 Other destabilized (via CF3 substitution) carbocations have been investigated by Ga~sman.~' 0' Me-C-C + ;* f* Me-C=C / I I Me \R Me \R Solvolyses of primary alkyl acridinium ions (6) in alcoholic solvents are proposed to proceed by SN2 reactions in nucleophilic solvents and via ion-molecule pairs in less nucleophilic solvents.36" In cases where rearrangement occurs (e.g. R = neopentyl) it is concluded that anchimeric assistance is absent.36a A study of secondary alkyl derivatives36b is also reported. The question of anchimeric assistance in solvolyses of secondary alkyl substrates rests heavily on the value of the a-deuterium isotope effect for limiting S,l solvolysis of a 2-propyl arenesulphonate as a model compound.A revised value of this isotope effect for trifluoroacetolysis (from 1.22 to 1.17) reveals that the reaction is not limiting.37 Earlier results for trifluoroacetolysis of secondary alkyl tosylates can now be interpreted in terms of either solvent or anchimeric assistance. Ab initio MO calculations confirm that the rearrangement attending solvolyses of simple neopentyl derivatives provides anchimeric a~sistance.~~ .. Ph The norbornyl cation controversy refuses to die. Formation of an ion pair is the rate-controlling step in the ethanolysis of endo-2-norbornyl mesylate since "0 n.m.r.studies reveal no sulphonate oxygen scrambling and hence no internal return.39 The em endo rate ratio of ca. lo3is thus confirmed and the extreme reluctance of 2-norbornyl cations to capture nucleophiles on the endo face is further exemplified. The bridging in 2-norb0rnyl~~" and bicyclo[2.2.2]octy140b cations is considered on the basis of substituent effects on solvolysis rates to involve all neighbouring C-C a-bonding electron pairs graded according to steric strain consequences. Deamina- tion studies of isomeric amines potentially capable of producing common delocalized 34 D. A. Dixon R. A. Eades R. Frey P. G. Gassman M. L. Hendewerk M. N. Paddon-Row and K. N. Houk J. Am. Chem. SOC. 1984 106 3885. 35 P. G. Gassman and J. B. Hall J.Am. Chem. SOC,1984,106,4267; P. G. Gassman and C. K. Harrington J. Org. Chem. 1984 49 2258. 36 (a) A. R. Katritzky Z. Dega-Szafran M. L. Lopez-Rodriguez and R. W. King J. Am. Chem. Soc. 1984 106 5577; (b) A. R. Katritzky M. L. Lopez-Rodriguez and J. Marquet J. Chem. SOC.,Perkin Trans. 2 1984 349. 37 H. Yamataka S. Tamura T. Hanafusa and T. Ando J. Chem. SOC.,Chem. Commun. 1984,362. 38 H. Yamataka T. Ando S. Nagase M. Hanamura and K. Morokuma J. Org. Chem. 1984 49 631. 39 C. Chang and W. J. le Noble J. Am. Chem. SOC.,1984 106 810. 40 (a) C. A. Grob and P. Sawlewicz Tetrahedron Lett. 1984,25,2973; (b) Helv. Chim. Acta 1984,67,1906. Reaction Mechanisms -Part (ii) Polar Reactions bicyclo[2.2.2]octyl cations reveal product differences and it is proposed that the non-classical ion has classical precursors which may also give rise to Rate studies and rate-product correlations for the solvolysis and aminolysis of benzoyl chloride point to SN2 character in these reactions.42 Establishment of a rate-product correlation for aminolysis over a 300-fold concentration range was achieved by using quantitative h.p.1.c.for both kinetic and product monitoring. The solvolyses of ring-substituted 4-dibromomethylphenoIs (7) in dioxane-water exhibit mechanistic complexities but at all acidities investigated quinone methides (8) are found as transient intermediates. Both carbocationic routes and a formal 1,6-elimination (EIcB) pathway (Scheme 1) are impli~ated.~~ Scheme 1 3 Other Nucleophilic Substitutions When a trimethyloxonium salt (Me30+) is treated with a strong hingered base C-C bond formation occurs.44 An oxonium ylide intermediate Me20-CHi is proposed which can then act as a nucleophile towards another molecule Me30+ to achieve C-C bond formation equation 2.Similarly the reaction of Me30+ with NaH yields C2 products whose isotopic composition is consistent with the inter- mediacy of an oxonium ~lide.~~" The action of singlet methylene on dialkyl ethers likewise produces oxonium ylides (directly) as well as products derived from normal C -H insertion^.^^ Most significantly the conversion of heterosubstituted methanes such as MeOH Me20 etc. into ethene and hydrocarbons derived therefrom can be achieved using bifunctional acidic-basic catalysts such as W03 on alumina.46 Oxonium ions uia SN2 reactions and oxonium ylides are the important intefmediates and ethene from MeOH is envisaged as arising from @elimination of Me20CH,CH3 (uia an equation 2 process) equation 3.Me26-EH2 + MebMe -+ Me26-CH2-CH + Me20 (2) Me26CH2CH CH2=CH2 + Me20 (3) 41 H. Maskill and A. A. Wilson J. Chem. Soc.. Perkin Trans. 2. 1984 119 1369. T. W. Bentley G. E. Carter and H. C. Harris J. Chem. Soc. Chem. Commun. 1984,387; T. W. Bentley and A. E. Freeman J. Chem. SOC.,Perkin Trans. 2 1984 1115. 43 P. B. D. de la Mare and P.A. Newman 1. Chem. SOC.,Perkin Tram. 2 1984 231 1797. 44 P. Rimmelin H. Taghavi and J. Sommer J. Chem. SOC.,Chem. Commun. 1984 1210. 45 (a) G. A. Olah H. Doggweiler and J. D. Felberg J.Org. Chem. 1984,49 2112; (b) 2116. 46 G. A. Olah H.Doggweiler J. D. Felberg S. Frohlich M. J. Grdina R. Karpeles T. Keumi S. Iuaba W. M. Ip K. Lammertsa G. Salem and D. C. Tabor J. Am. Chem. SOC.,1984 106 2143. 52 D. J. Mctennan The emphasis on oxonium ylides provides an answer to the question of C2 hydrocarbon formation in the Mobil methanol-to-gasoline process using the shape- and size-selective bifunctional ZSM-5zeolite catalyst whereby methane from natural gas can be converted via methanol into synthetic liquid gasoline. The first commer- cial plant is presently being constructed in New Zealand and it is satisfying to have some idea now of what will be going on in the catalytic reactors. A nucleophilic substitution reaction likewise appears in a proposed mechanism for carbonyl-assisted thermal dissolution of coal at high temperature^.^^ Even KIEs have a place in the study of coal conversion into more useful fuels,48“ and ionic pathways in superacid coal liquefaction (HF-BF,-H,) have been de~cribed.~” Industrial matters now make way for biologically-related studies.The role of metaphosphate ion PO, in the solvolysis of phosphate monoesters has been probed by studying the solvolysis of chiral phenyl [l60, 170 ‘80]phosphate?9 Complete inversion of configuration at P is observed so if PO is an intermediate equation 4 it mast not leave nor rotate within the solvent cage in which it is generated. It is 0 0 II Ph-ayG + PhOH + P=O ++ products (4) II I H 0-0-more plausible to suppose that backside pre-association of a nucleophilic solvent molecule occurs but whether this happens in a concerted SN2-like or in a stepwise fashion is ~ncertain.~’ In contrast migration of the phospho group from the 2-to the 1-position of phosphopropane-l,2-diol,equation 5 occurs with the retention of OH OH lo,7<& = 1;ky (5) OH configuration at P.” This results from an associative process in which a penta-coordinate intermediate must undergo a pseudorotation to yield the product.Two other groups concur in the rejection of a discrete metaphosphate intermediate. If a stepwise mechanism involving intermediates were operating one would expect a change in rate-limiting step and hence a break in the Bronsted plot as the basicities of nucleophiles were systematically changed yet the Bronsted plot for reaction of pyridines with pyridinio-N-phosphonates is linear.5’ Thus the process can be symbolized by equation 6 as involving a single transition-state.Consideration of the response of rate and equilibrium constants to changes in basicity of entering r 0 013-(6) 47 C. Choi and L. M. Stock J. Org. Chem. 1984,49 2871. 48 (a) K. R. Brower and J. Pajak J. Org. Chem 1984 49 3970; (b) G. A. Olah and A. Husain Fuel 1984 63 1427; G. A. Olah M. R. Bruce E. H. Edelson and A. Husain ibid. 1432. 49 S. L. Buchwald J. M. Friedman and J. R. Knowles J. Am. Chem. Soc. 1984 106 4911. S. L. Buchwald D. H. Pliura and J. R. Knowles J. Am. Chern. SOC.,1984 106 4916. 51 N. Bourne and A.Williams J. Am. Chem. SOC.,1984 106 7591. Reaction Mechanisms -Part (ii) Polar Reactions 53 and leaving groups suggests however that these are but weakly bonded to P in the transition state which will therefore possess a degree of metaphosphate character. A parallel study has produced similar results and a like conclusion; the transition state is seen as an open or ‘exploded’ Sulphonyl transfer is similarly concerted.52 The bicyclic phosphite (9) is a remarkably unreactive n~cleophile,~~ and steric effects cannot be invoked in view of the enhanced reactivity of species such as (9) (10) quinuclidine (10). In the systems studied (EtO),P is quite reactive.53 A stereoelec-tronic effect is advanced to account for these results. The results of ab initio MO calculations add credence to this hypothe~is.’~” Other stereoselective effects in phosphite reactions have been reported.54b Such stereoelectronic effects are of course related to the a-eff ect on nucleophilic reactivity which continues to attract attention.Both a caution on interpretation” and the view that the a-effect is a transition-state stabilization eff ect56 have been published. Both the kinetics of and the position of bond cleavage in the enzymatic and acid-catalysed hydrolysis of benzyl phosphate can be obtained from the l8Oisotope-induced shifts in the I3C and 31P n.m.r. spectra of the esters.57 Schowen’s hypothesis that compression of sN2 transition states is a necessary condition for enzymatic catalysis of methyl transfers has teen examined.MO calculations on the degenerate methyl transfer between MeNH and NH in the presence of a simple compression-attraction enzyme model indeed show that a compressed transition-state is selectively bound by the ‘en~yme’.’~ Calculated KIEs (CH Versus CD,) are in accord with the experimental values that originally gave rise to Schowen’s proposal. Other theoretical studies have explored areas of con- troversy and uncertainty. Pross and a co-worker have examined the acceleration of some SN2 reactions by a-carbonyl groups and a reactivity-selectivity anomaly thereof using the Pross-Shaik VBCM In these terms the carbanion (enolate) configuration (11) is seen to be the principal transition-state contributor amongst those commonly used to depict an SN2process Scheme 2 but only if the nucleophile Nu C..X e Nu 6 :X-e Nu? C :X-f) Nu C .X I I I II c=o c=o c=o C-0-Scheme 2 (11) 52 (a) M.T. Skoog and W. P. Jencks J. Am. Chem. Soc. 1984,106,7597; (b) P. D’Rozario R. L. Smyth and A. Williams ibid. 5027. 53 K. Taira W. L. Mock and D. G. Gorenstein J. Am. Chem. Soc. 1984 106 7831. 54 (a) K. Taira and D. G. Gorenstein J. Am. Chem. Soc. 1984 106 7825. (b) K. Taira and D. G. Gorenstein Tetrahedron 1984,40 3215; K. Taira T. Fanni and D. G. Gorenstein J. Org. Chem. 1984 49 4531. 55 S. Hoz and E. Buncel Tetrahedron Lett. 1984 25 3411. 56 M. Laloi-Diard P. Gesselin and F. Terrier Tetrahedron Lett. 1984 25 1267. 57 J. E. Parente J. M. Risley and R. L. Van Etten J. Am. Chem. Soc. 1984 106 8156.50 I. H. Williams J. Am. Chem. SOC.,1984 106 7206. 59 D. J. McLennan and A. Pross J. Chem. SOC. Perkin Trans. 2 1984 981. D. J. McLennan is a good electron donor. Computations and i.c.r. studies show that tetrahedral carbon and silicon differ in their behaviour towards nucleophiles ;5-co-ordinate Si anions appear to be stable but short-lived species!’ An MNDO study which leads to the conclusion that SN2 barriers at carbon are a consequence of the,small size of carbon inhibiting binding to five ligands6’ is seemingly at odds with the finding that SiI occupies a local minimum on the I- + Si14 potential surface.60 The crucial role of solvation in SN2‘61 and SN261’62 reactions has been theoretically probed and the importance of u*-T* orbital mixing in SNreactions at sp2 carbon (carbonyl and aromatic) has been empha~ized.~~ Attack of nucleophiles on acetyl chloride is rate-limiting rather than the break- down of a tetrahedral intermediate.64 It is concluded that the Ritchie N scale is not suitable for correlating acylation rates.Activation-volume measurements in particular provide evidence for rate-limiting attack of the piperidine nucleophile on an ion-molecule pair formed from (12) by pre-equilibrium heterolysi~.~’ This is the Ph most compelling item of evidence in favour of the operation of a Sneen-type S,2 mechanism under non-solvolytic conditions. It is significant that reaction through an apparently classical SN2 pathways competes. Bimolecular nucleophilic displace- ments at carbon-nitrogen double bonds are like those at C=C addition-elimination processes.66 In one case66a stereoelectronic control leads to a stereospecific reaction wherein the 2-chloride (13) produces the 2-azide by a retentive process whilst the E-chloride (14) reacts with inversion Scheme 3.Ar \ /OAc 7N3’ \OAc /C=N c1 Scheme 3 60 J. C. Sheldon R. N. Hayes and J. H. Bowie J. Am. Chem. Soc. 1984 106 7711. 61 F. Camon and M. J. S. Dewar J. Am. Chem. Soc. 1984 106 3531. 62 J. Chandrasekar S. F. Smith and W. L. Jorgensen J. Am. Chem. Soc. 1984 106 3049. 63 S. Yamabe T. Minato and Y. Kawabata Can. J. Chem. 1984 62 235. 64 D. J. Palling and W. P. Jencks J. Am. Chem. Soc. 1984 106 4869. 65 A. R. Katritzky K. Sakizadeh B. Gabrielsen and W.J. le Noble J. Am. Chem. SOC.,1984 106 1879. 66 (a) A. F. Hegarty and M. Mullane J. Chem. SOC.,Chem. Commun. 1984,913; (b)J. E. Rowe and A. F. Hegarty J. Org. Chem. 1984 49 3083. Reaction Mechanisms -Part (ii) Polar Reactions The archetypal SN2reaction is the Williamson ether synthesis using an alkoxide and an alkyl iodide. One example involving a primary (though neopentylic) iodide has been shown to go at least partly through an ET This is one of an ever-increasing number of cases of reactions hitherto thought to be polar two- electron processes that are falling to the axes of radical ion and radical pathway but survivors remain.68 4 Elimination Reactions It is difficult enough to measure a p-tritium secondary KIE in an elimination reaction equation 7 L = H or T since the isotope is in a labile position; interpretation is even more difficult when the kinetic effect is larger than the equilibrium isotope effect.Saunders has dealt with both the e~perimental~~" and theoretical problems69b and it transpires that such a &isotope effect can no longer be reliably accepted as an index of C-..H rupture at the transition state. The E2 exo-syn elimination of exo-norbornyl tosylate promoted by bulky alkoxides is reported to exhibit a temperature-independent primary kH/kD.70A bent C. -.H. -0arrangement is proposed to account for this but such interpretations have been ~hallenged.'~ In view of the demonstrations of E 1cB elimination from p-N0,C6H,CH2CH2NR3 substrates in recent years the reactions of the 2-(2,4-dinitrophenyl)ethylhalides are of interest.They are general base-catalysed and the Bronsted p-value increases in the order F = C1 > Br > I which is the inverse of the reactivity order. It is proposed that the mechanism is E2 with a major proton-transfer cornp~nent.~~ ArCHLCH,X + OR-+ ArCL=CH + X-+ ROH (7) Intramolecular base-promoted elimination of lactone (13; X = 0) to give (14; Y = COY) is surprisingly rapid and is general base-catalysed. Even though a proton alpha to carbonyl is removed an E2 mechanism is favoured on the grounds that strain in the 5-membered ring forces C-0 cleavage to accompany proton transfer.73" On the other hand curved buffer plots in the intramolecular elimination from the alkoxy-derivative (13; X = H2) to yield (14; Y = 0-)indicate a change in rate-limiting step and the intermediacy of an enolate anion73b The changeover (13) (14) 67 (a) E.C. Ashby D.-H. Bae W.-S. Park R. N. Depriest and W.-Y. Su Tetrahedron Lett. 1984 25 5107; (b) E. C. Ashby and J. N. Argyropoulos ibid. 7. 68 M. Newcomb and M. T. Burchill J. Am. Chem. Soc. 1984 106 8276. 69 (a) R. Subramanian and W. H. Saunders J. Am. Chern. Soc. 1984 106 7887; (b) W. H. Saunders ibid. 2223. 70 H. Kwart A. H. Gaffney and K. A. Wilk J. Chem. SOC.,Perkin Trans. 2 1984 565. 71 B. Anhede and N.-A. Bergman J. Am. Chem. Soc. 1984 106 7634. See also N. G. Rondan and K. N. Houk Tetrahedron Lett. 1984 25 2519. 72 J. R. Gandler and T. Yokoyama J. Am. Chem. SOC.,1984 106 130.73 (a) B. J. Mayer T. A. Spencer and K. D. Onan J. Am. Chem. SOC.,1984 106 6343; (b) B. J. Mayer and T. A. Spencer ibid. 6349. D. J. McLennan from E2 to ElcB is attributed to a diminution of nucleofugality as one goes from carboxylate to alkoxide. In another study of nucleofugality Issari and Stirling find that for once leaving-group rank and pK correlate in activated 1,3-eliminations from carbanions to form cycl~propanes.~~ Triose phosphates undergo non-enzymatic elimination and isomerization through a common enediolate intermediate Scheme 4 and catalysis studies show that the ElcB elimination proceeds via rate-limiting depr~tonation.~~ CH,OH -o\ C/H o\\ /H I -H+ -PO C L C=O II I I +H+ C CH ,O PO -HO CH,OPO:-HO/ %-I CHOH I CH,OPO:-Scheme 4 Further examples of E 1cB ester hydrolyses have been presented.Volume of activation studies confirm the earlier mechanistic assignment for p-HOC6H4CO2Ar (Ar = 2,4-dinitro~henyl).~~ The alkaline hydrolysis of thiocarbamate esters ArNHCO-SR involves the intermediacy of the isocyanate ArNCO which is formed from the thiocarbamate anion.77 The 1’3-dipole benzonitrile oxide can be formed by base-induced 1,3-dehydro- chlorination of the hydroxyimidoyl chlorides Scheme 5. The rate ratio kZ/kE is 6 x lo7 which represents a very large stereoelectronic effect indeed.78 Classical studies on alkyl halides and ‘onium’ salts are diminishing nevertheless the reason why the effect of successive P-methyl sutstitutions on the rates of Hofmann elimination from (R’CH,CH,)( R2CH2CH2)NMe20H- is non-additive has not yet been answered.After rejecting tunnelling and syn-elimination alterna- tives Saunders and co-workers account for this effect in terms of a sterically-induced shift in the transition-state character from ElcB-like towards a more central E2 character with increasing bulk at C,. Consequently substitution of a second p-methyl which is expected to favour a developing double bond leads to rate changes through a shift in transition-state character.79 74 B. Issari and C. J. M. Stirling J. Chem. SOC.,Perkin Trans. 2 1984 1043. 75 J. P. Richard J. Am. Chem. SOC.,1984 106 4926. 76 N. S. Isaacs and T. Najem J. Chem. Soc. Chem. Commun. 1984 1361; G. Cevasco G. Guanti S. Thea and A.Williams ibid. 783. 17 J. Mindle V. StErba V. Kadeifibek and J. Klicnar Coll. Czech. Chem. Commun. 1984 49 1577; N. Bourne A. Williams K. T. Douglas and T. R. Penkava J. Chem. SOC.,Perkin Trans. 2 1984 1827. 78 A. F. Hegarty and M. F. Mullane J. Chem. Soc. Chem. Commun. 1984 229. 19 S.-L. Wu Y.-T. Tao and W. H. Saunders J. Am. Chem. SOC.,1984 106 7583. Reaction Mechanisms -Part (ii) Polar Reactions Ph Ph OH \/ /c=N c1 It *H+ll Ph Ph 0-\/ ,C=N c1' + h PhCrN-0-Scheme 5 Phase transfer" and micellar" catalysis of elimination reactions has attracted attention and in the complete absence of solvent and catalyst gas-phase pyrolyses of alkyl acetates exhibit ion-pair characteristics as evidenced by the finding of strong anchimeric assistance being provided by the Me,N group.82 5 Addition Reactions A reliable method for obtaining values of k2 and k3 for mixed-order bromination of alkenes in non-polar solvents has been described.83 The question of bromonium ion formation in alkene bromination being reversible has been examined and examples provided.84 This has serious implications as far as structure-reactivity analysis is concerned since one must be sure that all alkenes in a series have the same rate-limiting step before making comparisons based on rates of bromination.Full details of intramolecular phenolate addition to unactivated double bonds have appeared. A primary carbanion is not formed since concerted general acid- catalysis is observed.85" Such reactions are considered to be models for enzyme- catalysed nucleophilic hydration of unactivated double bonds.On the other hand the analogous intramolecular addition of phenolate to unactivated triple bonds proceeds by way of a discrete vinyl carbanion and is some 104-times faster than cyclization of corresponding alkene~.~~ Evidence supporting the existence of weak nucleophilic solvent-assistance in the bromination of alkenes in protic solvents has been obtained. Data beautifully exemplifying the reactivity-selectivity principle are presented.86 80 J. Barry G. Bram G. Decodts A. Loupy P.Pigeon and J. Sansoulet J. Org. Chem. 1984,49 1138; M. Halpern Y. Sasson and M. Rabinovitz ibid. 2011. 81 E. Stadler D. Zanette M. C. Rezende and F. Nome J. Phys.Chem. 1984 88 1892. 82 G. Chuchani A. Rotinov R. M. Dominguez and N. Gonzalez J. Org. Chem. 1984,49 4157. 83 G. H. Schmid and B. Toyonaga J. Org. Chem. 1984,49 761. 84 R. S. Brown R. Gedye H. Slebocka-Tilk J. M. Buschek and K. R. Kopecky J. Am. Chem. Soc. 1984 106 4515. 85 (a) C. M. Evans and A. J. Kirby J. Chem. SOC.,Perkin Trans. 2 1984 1259; (b) 1269, 86 M.-F. Ruasse and B.-L. Zhang J. Org. Chem 1984,49 3207; M.-F. Ruasse and E. Lefebvre ibid. 3210. 58 D. J. McLennan An analysis of the preferred trajectory of approach of a nucleophile to a 7r-system considers both stabilizing HOMO-LUMO interactions and destabilizing HOMO- HOMO interaction^.'^ It is predicted that hard nucleophiles (low-lying HOMOs) will approach a 7r-centre at a smaller angle than soft nucleophiles (higher energy HOMOs).6 Aromatic Substitution and Rearrangements The Mills-Nixon effect concerns 7r-bond localization in polycyclic aromatic systems which was once thought to be of importance in determining rates and orientation in electrophilic substitution reactions. Clear evidence against ?r-localization has now been presented. An n.m.r. study of cyclobutane-annelated analogues of the dimethyl- dihydropyrene (15) shows that bond fixation is insignificant.” Ab initio MO calculations on protonated nitrous acid and on NO+ reveal that the former is best regarded as hydrated NO+.89” A similar conclusion is reached regarding protonated nitric acid and In both cases the production of electrophile by dehydration is calculated to be endoenergetic; it could indeed be the rate-limiting step in electrophilic attack upon reactive msystems.Nitrous acid is often a nuisance-impurity in nitration studies; the relative reac- tivities of several HN02 scavengers have been determined.” In 0.05 M acid 4-nitroaniline is the most efficient of those studied whilst in 1.3 M acid the scavenger of choice is NH,NH,+; urea is the least effective. The rate-limiting step is usually N-nitrosation and a study is reported wherein proton transfer between electronega- tive atoms is thought to be the rate-limiting step in the acid-catalysed decomposition of some N-nitroso comp~nds.~~ A sequence such as that in Scheme 6 (k- << k,) is advanced. k, RR’N-NO + H30+ -RR~~H-NO+ H,O k-I RR~~H-NO+ Y-2RR’NH + NOY NOY + scavenger -decomposition products Scheme 6 87 C.L. Liotta E. M. Burgess and W. H. Eberhardt J. Am. Chem. Soc. 1984 106 4849. 88 R. H. Mitchell P. D. Slowey T. Kamada R. V. Williams and P. J. Garrett J. Am. Chem. Soc. 1984 106 2431. 89 (a) M.-T. Nguyen and A. F. Hegarty J. Chem. Soc. Perkin Trans. 2 1984 2037; (b) 2043. 90 J. Fitzpatrick T. A. Meyer M. E. O’Neill and D. L. H. Williams J. Chem. Soc. Perkin Trans. 2 1984 927; L. R. Dix and D. L. H. Williams ibid. 109. 9’ S.S. Al-Kaabi G. Hallett T. A. Meyer and D. L. H. Williams J. Cbem. Soc. Perkin Trans.2,1984,1803. Reaction Mechanisms -Part (ii) Polar Reactions The Brown selectivity relationship concerning the correspondence of substrate (intermolecular) and positional (intramolecular) selectivity has often been observed in the breach for Friedel-Crafts alkylations.Careful studies are required to avoid isomerization and mixing complications and several are reported this year. Olah has investigated the alkylation of anisole and shows that under kinetic control the proportion of meta-product from this reactive substrate is small.92 De Haan and his (numerous) co-workers report both concordant and discordant cases using direct rather than competitive kinetic studies.93 Deviations are rationalized in terms of diffusion control. The cation radical ArCHz is the prime transient intermediate in the oxidative substitution of methylarenes by FelI1 complexes to yield benzylic The ET step is analysed in terms of Marcus theory and the non-equivalence of the measured a and the barrier position is emphasized.A detailed study of aromatic thallation reveals the presence of ArCH which is produced in an ET step with (CF3C02),T1+ as acceptor which in turn arises from the (CF3C02)3Tl reagent.95 The radical cation is important in side-chain substitution biaryl coupling and oxidative substitution. The (CF3C02)2Tl+ ion is also the active reagent in elec- trophilic (2-electron) nuclear thallation and while the question of whether the 1-electron and 2-electron processes proceed in parallel or by sequential pathways involving a common intermediate is not yet answered it is clear that the latter process possesses many of the characteristics of the former. No such difficulties exist with the Sandmeyer reaction induced by reducing cations single electron transfer to the diazonium cation is the rule and appears to be rate-limiting.96 A plausible mechanism involving nitrenium ions PhNH+ can be written for the acid-catalysed rearrangement of N-phenylhydroxylamines PhN( R)OH to the corre- sponding 4-aminophenols.Substituent effects however suggest that the intermediate is better represented by another resonance structure the imine-like structure (16).97 KIE studies have shown that two-proton catalysed benzidine rearrangements are concerted [5,5]-sigmatropic rearrangements. The same method now reveals that a one-proton rearrangement proceeds in a like fashion:* thus the rules of orbital symmetry govern the reaction irrespective of the proton count.Probing the nitramine rearrangement equation 8 in the same way yields a different result.99 A substantial 92 G. A. Olah J. A. Olah and T. Ohyama J. Am. Chem. Soc. 1984 106 5284. 93 F. P. De Haan G. L. Delker W. D. Covey J. Ahn M. S. Anisman E. C. Brehm J. Chang R. M. Chicz R. L. Cowan D. M. Ferrara C. H. Fong J. D. Harper C. D. Irani J. Y. Kim R. W. Meinhold K. D. Miller M. P. Roberts E. M.Stoler Y. J. Suh M. Tang and E. L. Williams J. Am. Chem. Soc. 1984 106 7038; see also earlier papers in the series. 94 C.J. Schlesener C. Amatore and J. K. Kochi J. Am. Chem. Soc. 1984 106 3567. W. Lau and J. K. Kochi J. Am. Chem Soc. 1984 106 7100. 95 96 C. Galli J. Chem. Soc. Perkin Trans. 2 1984 897. 97 G.Kohnstam W. A. Petch and D. L. H. Williams J. Chem. Soc. Perkin Trans. 2 1984 423. 98 H. J. Shine K. H. Park M. L. Brownawell and J. San Filippo J. Am. Chem. Soc. 1984 106 7077. 99 H. J. Shine J. Zygmunt M. L. Brownawell and J. San Filippo 1.Am. Chem. Soc. 1984 106 3610. D. J. McLennan MewO MeNH MeNH nitrogen (NO,) KIE is not accompanied by carbon KIEs of any magnitude. Thus N-N bond breaking is rate+limiting and earlier arguments in favour of the radical-cation-radical pair PhNHMe NO as an intermediate are strengthened. 7 Carbanions and Proton Transfer A6 initio calculations on the structures and stabilities of monomeric organo-lithium and -sodium compounds MCH2X provide a starting point for insight into syntheti- cally useful aggregated organometallics.Carbanions are more stabilized by a second- row element X and negative hyperconjugative and polarizability factors are cited.'" &Orbital effects are energetically unimportant in contradiction of earlier calcula- tions but do improve geometries. Stereoelectronic effects on the kinetic acidities of diastereotopic hydrogens have been theoretically examined and the results are in accordance with experimental findings on for example benzyl sulphoxides."' The trapping of fluorocarbanions by C02 has been achieved equation 9 and can be shown to be successful only when the most stable conformer of the carbanion has its lone pair anti to the position of the recently-entered nucleophile.102 A full account of cleavage of R-Si bonds in silanols RSiMe20H by OMe- in slightly aqueous methanol has appeared.lo3 For R = m-C1C6H4 and starting with the methyl ether the novel mechanism proposed (Scheme 7) avoids direct base attack at Si and involves a silanone intermediate.RSiMe,OMe + H20 eRSiMe,OH + MeOH RSiMe,OH + OMe-eRSiMe20-+ MeOH RSiMe20-__* R-+ Me2Si=0 R-+ MeOH -RH + OMe-Me,Si=O + MeOH -Me,Si(OMe)OH Thus the presence of OH or OMe on silicon can facilitate the removal of an R group from Si by dilute base which could be valuable in removal of protecting groups. Slow proton-transfers (N to 0)are reported for the deprotonation of monoproton- ated (and intramolecularly hydrogen-bonded) proton sponge.'04 It is contended that 100 P. von R. Schleyer T. Clark A. J. Kos G. W. Spitznagel C.Rohde D. had K. N. Houk and N. G. Rondan J. Am. Chem. SOC.,1984 106 6467. 101 S. Wolfe A. Stolow and L. A. La John Can. J. Chem. 1984 62 1470. 102 C. G. Krespan F. A. Van-Catledge and B. E. Smart J. Am. Chem. SOC.,1984 106 5544. 103 C. Eaborn and W. A. Stanczyk J. Chem. SOC.,Perkin Trans. 2 1984 2099. 104 G. B. Barnett and F. Hibbert J. Am. Chem. SOC.,1984 106 2080. Reaction Mechanisms -Part (ii) Polar Reactions the open form of the acid must be formed before proton loss can occur and that even then steric hindrance to proton transfer must be involved. Carbanions resulting from addition of MeO- to ArCH=CF2 are neutralized by solvent MeOH (MeOD) in a step having a primary KIE that increases with increasing temperature in some cases.lo5A two-step mechanism for protonation involving preassociation of MeOH with the carbanion allows the results to be rationalized.Carbanion production by the decarboxylation of (nitropheny1)acetate anions'06 and trichloroacetate ions'" is reported. In the latter case CCl; reacts as rapidly with 1,3,5-trinitrobenzene to form a Meisenheimer adduct as it does with H+in dimethyl sulphoxide. One of the clearest examples of stereoelectronic control of enolization is provided by the acid- and base-catalysed enolizations of trans-hexahydrofluorenone (17).'08 In a comparison with cyclohexyl phenyl ketone the substantially faster enolization of (17) (a rate factor of between 25 and 60) is in part attributed to the fact that the cleaving C-H bond is held rigidly parallel to the carbonyl .rr-orbital.Rates of proton transfer from transient methylarene cation radicals equation (9) have been successfully measured and cover a 105-fold range. Substantial primary KIEs are reported and the Bronsted a is ca. 0.28. ArCHj' + B + ArCH; + BH+ (10) Relative acidities of the cation radicals are also reported"' and Marcus theory parameters are derived which establish the reaction as being in the exergonic region of the driving force. 8 Carbonyl Derivatives and Tetrahedral Intermediates Stereoelectronic effects dominate the research in this area as is the case for some other areas. The variability of the C-0 single bond Fngth in ethers and esters R'-OR2 has been analysed; the resonance hybrid R'OR' is considered to be important and the C-0 bond lengthens as it acquires greater ionic character.' lo The exocyclic C-0 bond in axial compounds represented by (18) is systematically longer than in their equatorial analogues (19) and a bond length-reactivity correla- tion is obtained for hydrolyses in the (18) series where the stereoelectronic effect 105 H.F. Koch and A. S. Koch J. Am. Chem. SOC.,1984 106 4536. 106 E. Buncel T. K. Venkatachalam and B. C. Menon 1. Org. Chem 1984,49,413. 107 P. J. Atkins V. Gold and R. Marsh J. Chem. SOC., Perkin Trans. 2 1984 1239; P. J. Atkins V. Gold and W. N. Wassef ibid. 1984 1247. 108 R. M. Pollack R. H. Kayser and M. J. Cashen J. Org. Chem. 1984 49 3983. 109 C. J. Schlesener C. Amatore and J. K.Kochi J. Am. Chem.SOC.,1984 106 7472. 'lo F. H. Allen and A. J. Kirby J. Am. Chem. Soc. 1984 106 6197. D. J. McLennan OR ensures that molecules with a longer and more ionic C-0 bond gain a 'head start'."' These structure-reactivity correlations then allow a preliminary quantitative mapping of the reaction co-ordinate for spontaneous hydrolysis of axial cyclic acetals in terms of variable electron-demand at the departing oxygen.112 Sinnott and co-workers are not however as convinced that the steric relationship of an oxygen lone-pair with the axis of the cleaving bond is im~0rtant.l'~ In the case of spontaneous hydrolyses of pyridinium glycosides the stereoelectronic effect is considered to have at best a small accelerating effect after conformational factors are taken into account.Instead least-motion effects are favoured and stereoelec- tronic effects are seen as special cases rather than as dogma. However the principle of least motion may be inapplicable when extremely reactant- or product-like transition states are involved. It is noteworthy that least-motion effects were not ignored in Deslongchamps' 1983 monograph on stereoelectronic effects. Other interesting work on acetals114 and orthoe~ters'~~ has been reported. The f~rmation"'~and breakd~wn"'~ of a cyclic tetrahedral intermediate in a dead-end pathway accompanying the hydrolysis of the p-nitrobenzoate of pinacol equation 11 Ar = P-No2C6H4) have been studied. ArCOOCMe,CMe,O-Ar)(I$ -0 Rate and equilibrium data for the addition of nucleophiles to PhCOCF are reported,"6 which should be useful in allowing estimation of the behaviour of unstable tetrahedral intermediates.Extensive kinetic studies of the hydrolysis of ketene dithioacetals via initial C-protonation are reported."' The Thorpe-Ingold gem-dialkyl effect is manifested in the intramolecular car- boxyl-catalysed hydrolysis of sulphonamides ;it is rationalized in terms of (i) relief of unfavourable van der Waals interactions on proceeding from the initial to the transition state and (ii) the decrease in ring strain during activation."' X-ray crystallography establishes a splendid linear correlation between reactivity and the initial state S--0distance. 111 A. J. Briggs R. Glenn P. G. Jones A. J. Kirby and R. Ramaswany J.Am. Chem SOC. 1984,106,6200. 112 P. Jones and A. J. Kirby J. Am. Chem. SOC.,1984. 106 6207. 113 L. Hosie P. J. Marshall and M. L. Sinnott J. Chem. SOC.,Perkin Trans. 2 1984 1121. 114 R. A. Burt C. A. Chambers Y. Chiang C. S. Hillock A. J. Kresge and J. W. Larsen J. Org. Chem. 1984,49 2622. lL5 (a) R. A. McClelland N. E. Seaman and D. Cramm J. Am. Chem. SOC.,1984 106 4511; (b) R. A. McClelland ibid. 7579. 116 C. D. Ritchie J. Am. Chem. SOC. 1984 106 7187. 117 T. Okyama 1. Am. Chem. SOC.,1984 106 7134; T. Okuyama S. Kawao W. Fujiwara and T. Fueno J. Org. Chem. 1984 49 89; T. Okuyama S. Kawao and T. Fueno ibid. 85. 118 J. Jager. T. Graffland H. Schenk A. J. Kirby and J. B. F. N. Engberts,1.Am. Chem. SOC.,1984,106,139. Reaction Mechanisms -Part (ii) Polar Reactions A novel n.m.r.technique involving the l80isotope effect on 13C resonance^"^ has been used to monitor the oxygen exchange of a pyrylium cation in H2180. Acyclic dicarbonyl intermediates are proposed. The mechanism of p-lactam ring- opening in cephalosporins has been investigated in detail.12' Enzymatic transition- state analogues can be investigated by 13Cn.m.r.; the fact that a peptide aldehyde complexes with the serine active site of a-chymotrypsin in a hemiacetal form suggests that transition states bound by the enzyme may resemble hemiacetals.121 Weakly basic nucleophiles are normally ineffective in hydrolysing esters with more strongly basic leaving groups. The complexed zinc hydroxide (20) is an 20H exception; it is claimed that a metal-oxygen bond in the resulting tetrahedral intermediate cleaves more rapidly than the intermediate reverts to reactants.This has implications as far as metal ions co-ordinated close to enzyme active-sites are concerned.'22 In view of the large amount of work on carbon isotope effects in biological processes it is surprising that nothing is known on the hydration of C02 and the dehydration of HCO,. This gap has now been filled;'23 the respective k1Jk13 ratios at 24 "C are 1.0069and 1.0147,whilst the equilibrium isotope effect is 1.0077. The effective concentration of an intramolecular hydride-transfer to carbonyl carbon is several orders of magnitude higher than is normally found for proton transfer.'24 Tighter transition-states for the former process are suggested.The concept of virtual transition-states allows quantitation of &deuterium KIEs in all steps of hydrolysis of an a~etani1ide.l~~" Acyl substituent effects are similarly ana1~sed.l~~' This is a worthwhile advance since in both cases the interpretation of observed rate constants and KIEs is anything but straightforward. At moderately high concentrations of Br2 the acid-catalysed bromination of 2,4,6-trimethylacetophenoneis first-order in Br2 in contrast to the textbook case of the Lapworth zero-order result.'26 A systematic investigation of the thermodynamics of ionization of P-di- and tri-carbonyl compounds has been provided together with 119 J. M. Risley R. L. Van Etten C. Uncuta and A. T. Balaban J.Am. Cbem. SOC.,1984 106 7836. 120 M. I. Page and P. Proctor 1. Am. Cbem. SOC.,1984 106 3820. 121 D. 0. Shah K. Lai and D. G. Gorenstein J. Am. Cbem. SOC., 1984 106 4272. 122 J. Chin and X. Zou J. Am. Cbem. SOC.,1984 106 3687. 123 J. F. Marlier and M. H. O'Leary J. Am. Cbem. SOC., 1984 106 5055. 124 A. M. Davis M. I. Page S. C. Mason and I. Watt J. Cbem SOC., Cbem. Commun. 1984 1671. 125 (a) R. L. Stein H. Fujihara D. M. Quinn G. Fischer G. Kullertz A. Earth and R. L. Schowen J. Am. Cbem. SOC.,1984 106 1457; (b)J. K. Young S. Pazhanisamy and R. L. Schowen J. Org. Cbem. 1984,49 4148. A. G. Pinkus and R. Gopalan J. Am. Cbem. Soc. 1984 106. 2630. 12' 64 D. J. McLennan association constants for pairing of the enolate ions to alkali-metal cation^.'^' The patterns fit what the authors ciaim is 'common knowledge' but a caution against over-interpretation of small (<2 kcal mol-') rate or product differences is issued.9 Some Probes of Polar Mechanisms Included in this section are discussions of some of the tools used to probe the mechanisms of polar reactions -substituent effects and free energy relationships (linear and otherwise) solvent effects and isotope effects. The validity of Swain's 1983 fF + rR dual substituent parameter equation has been questioned. The separation of field and resonance effects and the fixed R scale give the greatest cause for concern.12* Similarly the aA + bB solvent-effect equation has been adversely critici~td.'~~ Swain has replied to criticisms and has emphasized his intention of simplifying analyses over those used in for instance the plat + pRi?R DSP equation where the best of four oRscales is picked Another DSP equation having but one resonance scale has been propo~ed.'~' For what it is worth the DSP equation is superior to Swain in correlating 13C 'H and vco spectral parameters for substituted acetanilides and 4-nitrophenylben~oates.'~~ What is more significant is that there are excellent intercorrelations amongst these and between them and hydrolysis rates and solution basicities even for cases where DSP and Swain correlations are bad.Ab initio calculations are used to derive a scale of pure field-effe~ts'~~" and to analyse the polarization of 7r-electron systems by substituent dipoles and poles.'33b Alkyl inductive effects have been analysed in terms of base constants to which are added numbers characteristic of the group connectivity of carbon atoms in the various groups.'34 The influence of solvent on the inductive order of substituents has been probed by i.r.methods; oIcorrelates results except for H-bond acceptor substituents in H-bond donor solvents and H-bond donor substituents in H-bond acceptor solvents. In the amphoteric solvent MeOH the above effects cancel and a true inductive order is ~bserved.'~' Enhanced substituent solvation-assisted reson- ance effects are observed for phenol ionization in solvents such as DMS0.'36 The Hammett p value for phenol ionization in DMSO (5.3) lies between the H20and the gas-phase value thus less stabilized anions with localized charge (gas phase) are more stabilized in polar solvents and acidity differences are le~elled.'~' 'Through 127 E.M. Amett S. G. Maroldo S. L. Schilling and J. A. Harrelson J. Am. Chem. Soc. 1984 106 6759. 12* W. F. Reynolds and R. D. Topsom J. Org. Chem. 1984,49 1989; A. J. Hoefnagel W. Oosterbeek and B. M. Wepster ibid. 1993; M. Charton ibid. 1997. 129 R. W. Taft J.-L. M. Abboud and M. J. Kamlet J. Org. Chem. 1984 49 2001; D. N. Kevill J. Chem. Research (S) 1984 86. 130 C. G. Swain J. Org. Chem. 1984 49 2005. 131 1. B. Afanas'ev J. Chem. SOC.,Perkin Trans. 2 1984 1589. 132 C. J. O'Connor D. J. McLennan D. J. Calvert T. D. Lomax A. J. Porter and D. A. Rogers Aust. J. Chem..1984 37 497. 133 (a) S. Mamott and R. D. Topsom J. Am. Chem. SOC.,1984 106 7; (b)1. Chem SOC.,Perkin Trans. 2 1984 113. 134 P.Hanson J. Chem. Soc. Perkin Trans. 2 1984 101. 135 C. Laurence M. Berthelot M. Lucon M. Helbert D. G. Moms and J.-F. Gal J. Chem. SOC.,Perkin Trans. 2 1984 705. 136 M. Mashirna R.T. McIver R. W. Taft F. G. Bordwell and W. N. Olmsted 1.Am. Chem. Soc. 1984 106 2717. 137 F. G. Bordwell R. J. McCallum and W. N. Olmsted J. Org. Chem. 1984 49 1424. Reaction Mechanisms -Part (ii) Polar Reactions 65 resonance' is usually invoked to explain the influence of a para-nitro group on the properties of aniline and phenol; VB analyses based on ab initio wavefunctions suggest that through resonance is negligible and that ring polarization has a greater effect than charge transfer.'38 Some 30 years ago H.C. Brown correctly surmized that a steric effect caused 2,6-di-t-butylpyridine to exhibit an anomalously low basicity in solution but the exact nature of the effect has since been the subject of debate. A combination of gas-phase and aqueous-solution measurements now shows that both the neutral and protonated forms are substantially solvated in water but for the latter the barriers to internal rotation for the water molecule and the substituents are am~1ified.l~' This accords with the entropic origin of the lowered basicity. The ubiquitous Marcus equation for proton (and electron) transfer predicts the Bronsted Q = 0.5 for a particle half-transferred at the transition state.Analysis of the dependence of AG* on AGO for a reaction series using different barrier models reveals that this may not necessarily be the case.'4o The qualitative VB treatment of Pross and Shaik lends credence to this view. Pross shows that two-configuration (i.e. reactant and product) systems are likely to exhibit normal behaviour e.g. SN2 methyl transfers but that in multi-configuration systems e.g. SN2 benzyl transfer or nitroalkane deprotonation anomalous rate-equilibrium relationships are likely and depend as much on the position of the probe relative to the reaction site as on the reaction type. A provocative suggestion is that even in a simple SN2 reaction charge may be 50% transferred at the transition state no matter where it lies on the reaction co-ordinate in the geometric sense.14' Simple Marcus theory is of course a quantitative expression of the Bell-Evans-Polyani-Leffler-Hammond principle which deals with parallel effects in the reactant-product dimension.Kreevoy and Lee now introduce factors related to perpendicular effects operating in the loose-tight dimension and show that for hydride transfers between NAD+ analogues the measured Bronsted a is not an index of the degree of hydride transfer.'42 Marcus theory can also be used to predict the existence or otherwise of transition states using the relative magnitudes of AGO and the intrinsic barrier AG;. The predictions for gas-phase deprotonations of C-acids (by ab initio MO calculations) are verified.'43 The Marcus equation correctly predicts the Bronsted slope for the gas-phase reaction of CH3Br with substituted benzyl anions.'44 Two papers by Murdoch consider further Marcus business.In the the proposition that AG; should be the arithmetic mean of the AG* values of the two identity reactions is examined using models from SCF-MO calculations and is found to hold in most cases. The second'45b considers cases such as internal rotation and conformational rearrangements where no identity reactions exist and a novel method for obtaining AG is developed. 138 P. C. Hiberty and G. Ohanessian J. Am. Chem. SOC.,1984 106 6963. 139 H. P. Hopkins D. V. Jahagirdar P. S. Moulik D. H. Aue H. M. Webb W. R. Davidson and M. D. Pedley J. Am. Chem. SOC.,1984 106,4341. 140 F. Wiseman and N.R. Kestner J. Phys. Chem. 1984 88 4354. 141 A. Pross J. Org. Chem. 1984 49 1811. 142 M. M. Kreevoy and I.& H. Lee J. Am. Chem. SOC.,1984 106 2550. 143 S. Wolfe Can. J. Chem. 1984 62 1465. 144 J. A. Dodd and J. I. Brauman J. Am. Chem. SOC.,1984 106 5356. 145 (a) J. Donnella and J. R. Murdoch J. Am. Chem. SOC.,1984 106 4724; (6) M. Y. Chen and J. R. Murdoch ibid. 4735. 66 D. J. McLennan The arithmetic mean aspect of the Marcus equation has been experimentally tested for sN2 methyl transfers of arenesulphonates and is found to hold (quadratic term omitted hence linear Hammett and Bronsted plots).l4 Surprisingly the Ham- mett p for ArS0; + CH303SAr identity reactions is 0.6 and the Kreevoy-Ross idea of a looser transition-state is provided as a rationalization.Linear Bronsted plots are also generated by the SN2 reactions of nitranions derived from carbazoles phenothiazines and diphenylamides with benzyl chlorides in DMS0147 and it is shown that anion basicity is the primary factor in controlling nucleophilicities of nitranions carbanions and oxyanions. Surprisingly neutral amines are 10-100times more nucleophilic than comparably basic nitranions. The Marcus equation is also a quantitative expression of the much-debated reactivity-selectivity principle (RSP),which in turn requires multiple substitution for exemplification. Dubois and co-workers have examined multiple substituent effects in the context of the Hammett equation and find a cross-term is usually significant thus guaranteeing n~n-additivity.'~~" The cross-coefficient is then a measure of substituent-induced transition-state structural changes which may none- theless be compatible with linear individual Hammett plots.The contribution of transition-state variation to p variation has been assessed for carbocation-forming alkene br~minations'~~~ and conditions for the applicability or otherwise of the RSP have been established. Both p and Winstein-Grunwald rn values obtained from rates of bromination of styrenes ArC(Y)=CH2 vary with Y in a beautiful RSP fa~hi0n.l~~ The reactivity order of bases in nitroethane deprotonation is tertiary amines > secondary and primary amines > oxyanions. Electrostatic effects are in~0ked.l~' The Bronsted p parameters are in accord with the RSP and in such a case are expected to be a valid measure of the extent of charge (and perhaps proton) transfer at the transition state.141 If KIEs are regarded as a measure of transition-state structure the variation of primary carbon and secondary hydrogen isotope effects in the SN2 reactions of substituted dimethylanilines with benzyl arenesulphonates variously substituted in both ringslsl constitutes the finest piece of evidence in favour of transition-state variation in accordance with the Thornton-More O'Ferrall-Jencks rules yet pro- vided.Both parallel and perpendicular shifts are beautifully illustrated. Modification of the Marcus equation allows quantitative rationalization of trends in primary kH/kD values with changing ApK in proton transfer reactions.152 The question of whether hydride transfers in NADH/NAD+ systems proceed via linear or bent transition-state structures has been investigated using MNDO ;the former alternative is fa~0ured.l~~ Secondary deuterium isotope effects in SE2reactions are reported for the first time,154 for electrophilic attack on dialkylmercurials.Alpha 146 E. S. Lewis and D. D. Hu J. Am. Chem. Soc. 1984 106 3292. 147 F. G. Bordwell and D. L. Hughes J. Am. Chem. Soc 1984 106 3234. 14' (a)J.-E. Dubois M.-F. Ruasse and A. Argile J. Am. Chem. SOC.,1984 106 4840; (b)4846. 149 M.-F. Ruasse and J.-E. Dubois J. Am. Chem. Soc. 1984 106 3230. 150 P. Y. Bruice J. Am. Chem. SOC.,1984 106 5959. 15' T. Ando H. Tanabe and Y. Yamataka J. Am.Chem Soc. 1984 106 2084. 152 D. J. Hupe and E. R. Pohl J. Am. Chem. Soc. 1984 106 5634. 153 S. M. van der Kerk W. van Gerresheim and J. W. Verhoeven Rec. Truv. Chim. Pays-Bus.,1984,103,143. 154 D. J. Nencivengo M. L. Brownawell M.-Y. Li and J. San Filippo J. Am. Chem. Soc. 1984 106 3703. Reaction Mechanisms -Part (ii) Polar Reactions effects are large which is surprising in terms of SN1-SN2theory if a pentaco-ordinate transition state is involved but bond stretching factors may outweigh angle bending factors in SE2. Isotope effects b/k14 for enzyme-catalysed transmethylation from S-adenosyl- methionine to the rneta- and para-positions of dopamine are markedly and surpris- ingly different.155 para-Methylation seems to be normal SN2,but the isotope effect for rneta may be ‘diluted’ by a binding step or a conformational change.The primary (and perhaps the secondary) deuterium isotope effects for enzymatic oxidation of glucose 6-phosphate by TPN are different in H20and D20? Thus hydride transfer to TPN may be coupled with transfer of the OH proton to an enzyme site with tunnelling playing an important role. A major disincentive to the evaluation of deuterium isotope effects is the effort needed to synthesize the labelled substrate. When intramolecular competition between hydrogen isotopes is involved measurement by natural abundance ’H n.m.r. may obviate this diffic~lty.’’~ 155 S.-E. Wu W. P. Huskey R. T. Borchardt and R. L. Schowen J. Am. Chem. SOC.,1984 106 5762. 156 J. D.Hermes and W. W. Cleland J. Am. Chem. SOC.,1984 106 7263. 157 R. A. Pascal M. W. Baum C. K. Wagner and L. R. Rodgers J. Am. Chem. Soc. 1984 106 5377.