3 Theoretical Organic Chemistry By J. J. W. McDOUALL Department of Chemistry University of Manchester Manchester M13 9PL 1 Introduction In preparing this review the very wide diversity of models for studying organic structure and reactivity has emerged quite clearly and what follows is of necessity a personal perspective. In ab initio semiempirical and molecular mechanical schemes the centre stage is still occupied by those methods which have had a long history of application for example in ab initio theory the Hartree-Fock (HF) approach is still unchallenged as the standard starting point for a discussion of electronic structure. Yet in what appears to be some of the most ‘informative’ modelling (in the opinion of this reviewer) there seems to be a push away from standard schemes towards methods which yield in addition to a molecular energy some further insight into the nature of the molecular architecture under investigation.The most useful and transferable insights do not necessarily emerge from the use of the most refined/state-of-the-art wavefunctions but rather from an approach’ that looks beyond the confines of a particular method (or in practice a particular computational package). It is becoming increasingly easier for everyone to use standard computational packages and while this leads to an ever larger database of computational chemistry,2 the rationalization of this ‘data’ through the use and development of qualitative ideas (which are central to theoretical organic chemistry) appears to lag behind.2 Methods A collection of useful reviews has appeared3 covering a wide range of methodology. As Professor E. R. Davidson says in his introduction to the volume ‘There are now a vast array of numerical results and a few new ideas which could not have been foreseen 20 years ago. Unfortunately the growth in thisJield has also led to repeated bifurcations into microjields so that it is now nearly impossible for one person to comprehend the whole jield. It is hoped that the present review will put a few of these microjields into perspective’. There are a number of articles in this volume which are of particular relevance to organic chemistry. These include the discussion of density D. M. Prosperio R.Hoffmann and R.D. Levin J. Am. Chem. Soc. 1991 113 3217.I ’Quantum chemistry literature database. Supplement 10. Bibliography of a6 initio calculations for 1989 ed. K. Ohno K. Morokuma and H. Hosoya THEOCHEM 1991 84 1. E. R. Davidson (Ed.) Chem. Reu. 1991 91(5). 39 J. J. W. McDouall functional theory by Ziegler? Following an overview of the general theory and computational considerations the approximate density functional theory is assessed through its application to bond energy calculations conformational analysis reac- tion paths and transition state structures. The examples are mainly taken from organometallic reactions where the more demanding HF calculations would be difficult. Gerratt and co-workers also provide a complete review of the applications of the spin-coupled valence bond meth~d.~ Again the basic theory is outlined but the emphasis is on the applications and the unique insights offered by this compact and elegant approach.Finally the review of Veillard6 should be mentioned which discusses ab initio calculations of the structure and molecular properties of organometallic systems. In dealing with open-shell systems the two standard approaches in ab initio theory are the unrestricted and restricted open-shell Hartree-Fock methods UHF and ROHF respectively. The UHF method suffers from the problem of spin contamina- tion which leads to poor convergence of the perturbation series for estimating the correlation energy. ROHF on the other hand does not suffer from the spin contami- nation problem but formulation of perturbation theory for it is more difficult.Knowles et aL7 have put forward a transparent formalism for computing the correla- tion energy from a Mdler-Plesset type perturbation series for an ROHF reference function. The method employs semi-canonical orbitals and while Q and p type spin orbitals do possess spatially different forms the spin contamination problem is avoided. Application to NH2 and CN shows this approach leads to a faster conver- gence of the perturbation series than the corresponding UHF based theory. A number of other interesting methodological developments have been reported amongst which should be mentioned the evaluation of analytical gradients in pseudospectral HF theory.8" The pseudospectral schemes provide numerical solu- tions to the HF equations*b-d and eliminate the need to evaluate the vast number of two-electron integrals making them suitable for application to larger molecular problems.At present pseudospectral calculations on a range of molecules (using up to 100 basis functions) show deviations in computed bond lengths of *0.003 A and *lo in bond angles when compared with conventional HF methods. The molecular electrostatic potential (MEP) of molecules is frequently used as a guide to regions of chemical attack/reactivity in a molecule. The MEP is usually evaluated from HF wavefunctions. An interesting study on the effect of electron correlation on the distribution of MEP shows that in HF N2 CO HCN H20 and formaldehyde electron correlation has a significant effect on the MEP near the nuclei.However the MEP determined from SCF wavefunctions remains largely unaffected in regions located outside the van der Waals sphere. T. Ziegler Chem. Rev. 1991 91 651. ' D. L. Cooper J. Gerratt and M. Raimondi Chem. Rev. 1991 91 929. A. Veillard Chern. Rev. 1991 91 743. ' P. J. Knowles J. S. Andrews R. D. Amos N.C. Handy and J. A. Pople Chem. Phys. Lett. 1991 186 130. (a) Y. Won J,-G. Lee M. N.Ringnalda and R. A. Friesner J. Chem. Phys. 1991,94 8152; (b) R. A. Friesner Chem. Phys. Lett. 1985,116,39; J. Chem. Phys. 1986,85 1462; J. Chem. Phys. 1987,86,3522; J. Phys. Chem. 1988,92 3091; (c) M. N.Ringnalda Y. Won and R. A. Friesner J. Chem. Phys. 1990 92 1163; (d) J.-M. Langlois R. P. Muller T. R. Coley W. A. Goddard 111 M. N. Ringnalda Y. Won and R.A. Friesner J. Chem. Phys. 1990 92 7488. F. J. Luque M. Orozco F. Illas and J. Rubio J. Am. Chem. SOC.,1991 113 5203. Theoretical Organic Chemistry 41 A new force field has been developed for studying transition metal complexes." The scheme is called SHAPES and uses a new treatment of angular distortion (three-body) terms based on angular overlap considerations. Angular potential energies are expressed as periodic Fourier terms in spherical internal coordinates. This formulation provides a generalized description of many idealized geometries. For example good accuracy is obtained for a variety of square-planar rhodium complexes (RMS deviation for bond lengths is +0.02 8 and *3' for angles). Finally the electron localization function (ELF) of Becke and Edgecombe"" has been applied to a wide range of small molecules using a new program called GRAPA" which provides high quality graphical output.The ELF maps the electron pair probability distribution and generates interesting pictures of atomic shells core binding and lone pair regions in molecules. The ELF has the important property of being invariant under certain unitary transformations. 3 Bonding and Molecular Structure The interesting series of papers by Messmer on the generalized valence bond (GVB) description of hypervalent molecules continues." The classical interpretation of hypervalency in terms of resonance structures is replaced by a single configuration description which arises when orthogonality constraints are removed from the orbitals.The ONF3 and OPF systems have been studied12" and the N-0 bond in the former is found to be composed of a single bond and three back-bonds while the 0-P bond is a genuine triple bond. The GVB lone pairs in ONF3 are significantly polarized toward N indicating back-bonding. A study of the stabilities of C3Hf and C3H2F; cations' shows that fluorine migration which converts CH2=C+CF3 to the allylic cation CH,=CFCF'; is exother- mic by 31.5 kcalt mol-' with a barrier involving a bridged fluoronium ion of only 6.1 kcal mol-'. Rearrangement of CH,=CfCF3 to CHF=CHCF; is exothermic by 44.9 kcal mol-' and occurs via a multistep process including 1,3 fluorine migration with no barrier higher than 0.3 kcal mol-'. On the basis of this study the authors suggest that CH2=C+CF3 is a good candidate for experimental work on fluorine migration'in carbocations.In substituted ethylene dications of the form C2X2Yi+ it is found14 that C2Fi+ C,(OH);+ C2H2(NH2):+ and C2(OH),(NH2):+ are planar while C2HZ+ C2(NH2);+ and C,(SH)i+ have a twisted structure. The substituents X with lone pair orbitals strongly donate charge into the formally empty carbon T orbitals of C2X;+ yielding partial C-X double bonds. If X is a first row atom conjugation of the resulting double bonds causes the minimum energy conformation to be planar provided that steric repulsion of the vicinal groups is absent. 10 V.S. Allured C. M. Kelly and C. R. Landis J. Am. Chem. Soc. 1991 113 1. " (a) A. D. Becke and K. E. Edgecombe J. Chem.Phys. 1990 92 5397; (b) J. Flad F.-X. Fraschio and B. Miehlich Angew. Chem. Int. Ed. EngZ. 1991,30,409; (c) GRAPA program Institute fir Theoretische Chemie der Universitat Stuttgart 1989. 12 (a) R. P. Messmer J. Am. Chem. SOC.,1991 113 433; (b) P. A. Schultz and R. P. Messmer J. Am. Chem. SOC.,1988 110 8258; (c) C. H. Patterson and R. P. Messmer J. Am. Chem. SOC.,1989 111,8059; (d) C. H. Patterson and R.P. Messmer J. Am. Chem. SOC.,1990 112 4138. l3 M. McAllister T. T. Tidwell M. R. Peterson and I. G. Csizmadia J. Org. Chern. 1991 56 575. l4 G. Frenking J. Am. Chem. SOC.,1991 113 2476. t 1 cal = 4.1845 J. J. W McDouall A twisted double bond in methylenephosphonium ions (R,N),P+=C(SiR;) has also been rep~rted.'~ The twisting of the P+=C double bond is caused by steric hindrance of bulky R and R' groups and facilitated by the electronic structure of the parent compound (R,N),P+=C(SiR;) ,which differs from the genuine double bond structure of H2P+=CH2.For R = R = H there is a rotational barrier of 20 kcal mol-'. A detailed conformational analysis of cyanoguanidine including its tautomer and their respective radical anions,16 shows that when the anion is formed a sizeable fraction of the resonance stabilization of the guanidine moiety is lost and as a consequence there is a greater tendency for the amino groups to rotate out of plane and pyramidalize. Two structures have been located for the 4-protioadamantyl cation (ClOH~,)," one of C symmetry (l) and the other of C1 symmetry (2).Structure (1) lies 8 kJ mol-' higher in energy than (2). It is suggested that (1) is the primary intermedi- ate in the solvolysis of 4-endo-protioadamantyl derivatives while (2) is the primary intermediate in the solvolysis of 4-exo-protioadamantyl derivatives. The benzene dication exists in both a singlet and triplet state. The singlet structure is found to possess a chair-like CZh symmetry while the triplet structure is planar with D6hsymmetry." The strength of T bonds in acetylene and ethylene and their effect on the relative energies of 7r bond addition reactions have been analyzed using CISD/6-3 1G** cal~ulations.'~ Isodesmic reaction schemes were used to obtain bond strengths ionization potentials and electron affinities. Very good agreement with experiment is obtained from the isodesmic approach.The T bond in acetylene is found to require 12 kcal mol-' more energy for dissociation than the T bond in ethylene. The bonding of transition metal ions to acetylene has been investigated at a correlated level of theory." The ions on the left hand side of the first and second transition rows (Sc+-V+ and Y+-Mo+ respectively) insert into the 7r bond to form a three-membered ring but on the right hand side of the rows the bonding is mainly electrostatic. The increased stretching frequency (=C= N-) observed on protonation of Schiffs bases in retinoids and other related systems may be attributed to an increased bond energy for both the single and double bond.21 The lowest unoccupied molecular M. Ehrig H.Horn C. Kolmel and R. Ahlrichs J. Am. Chem. Soc. 1991 113 3701. 16 R. D. Bach J. J. W. McDouall A. L. Owensby H. B. Schlegel J. W. Holubka and J. C. Ball J. Phys. Org. Chem. 1991 4 125. R. Dutter A. Rauk S. M. Whitworth and T. S. Sorensen J. Am. Chem. Soc. 1991 113 411. l8 K. Krogh-Jespersen J. Am. Chem. Soc. 1991 ll? 417. 19 A. Nicolaides and W. T. Borden J. Am. Chem. Soc. 1991 113 6750. 20 M. Sodupe and C. W. Bauschlicher Jr. J. Phys. Chem. 1991 95 8640. 21 D. Bond J. Am. Chem. Soc. 1991 113 385. Theoretical Organic Chemistry orbitals (LUMOs) corresponding to both bonds have negative energies giving enhanced reactivity toward nucleophilic addition of Schiffs bases. Two symmetric (3 (c2h) 4 (c2h)) and two asymmetric (5 (anti),6 (syn))formic acid -formate anion dimers exhibiting strong hydrogen bonds have been deter- mined.22 The existence of all these experimentally and the small calculated differen- ces in energy point to the sensitivity of conformation to molecular environment.Hydrogen bonded complexes between hydrogen fluoride and hydroxylamine have been ~alculated~~" confirming the novel ring structures suggested in reference 23(b). 0 H 0 H H-C / \c-0 H-C / \c-0 \o...H. / \O-H*.. 0/ 0 (5) (6) The 1 :1 complex (7) is predicted to be a loosely bound ring with a strong N-HF bond and a weak HF-NO bond with an association enthalpy of between -6 and -9 kcal mol-'. For the 2 1 complex (8) the second H-F is inserted between the first H-F moiety and OH group and possesses three strong hydrogen bonds with an association enthalpy between -17 and -19 kcal mol-'.Finally two interesting conformational studies should be mentioned. The first concerns the conformational potential energy surface of glycine obtained with a variety of computational which is then used to generate Boltzmann equilibrium distributions and the kinetics of conformational interconversion at various temperatures. The second is concerned with the conformational properties of N-formylglycine dithio acid.25 Three conformations were found and a description emerges of the N-.S nonbonded interaction which has implications for the structure and reactivity of enzyme-substrate complexes which incorporate a similar contact. 22 H. Basch and W. J.Stevens J. Am. Chem. SOC.,1991 113 95. 23 (a) R. E. Brown Q. Zhang and R. J. Bartlett J. Am. Chem. SOC.,1991 113 5248; (6) R. Lascola and L. Andrews J. Am. Chem. SOC.,1987 109 4765. 24 J. H. Jensen and M. S. Gordon J. Am. Chem. SOC.,1991 113 7917. 25 R. Fausto J. J. C. Teixeira-Dias and P. R. Carey J. Am. Chem. SOC.,1991 113 2471 J. J. W McDouall 4 Beyond the Gas Phase Recently there has been much effort directed at the development of models which allow the inclusion of solvent effects into quantum mechanical descriptions of solute molecules. Activity in this important field is growing and it seems appropriate to give a guide to the current literature. What follows is a mixture of methodology and applications including the use of molecular dynamics (MD) simulations and free energy perturbation (FEP) methods as well as continuum models of the solvent.The most simple models (from a computational point of view) appear to be those based on a continuum representation of the solvent. In these models the solute is represented by a quantum mechanical wavefunction and ensconced in a cavity which is surrounded by a medium of continuous dielectric constant representing the solvent. The effect of the solvent medium on the solute is usually incorporated by adding appropriate terms to the one-electron Fock operator and recalculating the molecular orbitals self consistently. This process gives what is termed the self consistent reaction field (SCRF). Tomasi and coworkers26 have provided a concise overview of the theoretical methods based on a continuous distribution of solvent molecules (the continuum dielectric model being the most important).The optimiz- ation of solutes in the presence of a SCRF is important in assessing the effect of solvent on the geometric structure of the solute.27 The use of correlated wavefunctions in reaction field (RF) methods has been developed to include the MP2 and quadratic configuration interaction (QCI) methods with geometry optimization.28 For semi- empirical wavefunctions similar methods have been developed but a study shows that significant errors in the calculated energies of some polar molecules can result if geometry optimization is carried out using approximate gradients which assume a first-order invariance of the density matrix with respect to geometry.29 The AM1 method has been used to investigate RF effects on the tautomeric equilibria of nucleic acid pyrimidine and purine bases and their 1-methyl analogues in water solvent.30 In most cases the same tautomer is predicted to be most stable in the gas phase and solution but the relative stabilities show significant differences which have a substantial effect on nucleic acid base pairing/mis-pairing probability esti- mates.Another application of the AM1-SCRF method to the calculation of radical formation energies for the process R”R’RCH $ R”R’RC’ + H’ in the gas phase and solution,31 indicates that the homolytic dissociation energies of C-H bonds in polar solvents are satisfactorily reproduced but the dissociation paths are not.The comparison of reactions in solution using discrete and continuum representa- tions of the solvent can shed light on the performance of continuum models. A study of neutral and zwitterionic forms of the amino acids glycine alanine and pr01ine~~ suggests that a combined approach in which some solvent molecules are included in the solute cavity and the bulk treated by SCRF methods may be the 26 J. J. Tomasi R. Bonaccorsi R. Cammi and F. J. Olivares de Valle J. Mol. Struct. (THEOCHEM) 1991 234 401. 27 R. Bonaccorsi R. Cammi and J. Tomasi J. Comput. Chem. 1991 12 301. 28 M. W. Wong M. J. Frisch and K. B. Wiberg J. Am. Chem. SOC.,1991 113 4776. 29 H. S. Rzepa M. Yi M. M. Karelson and M. C. Zerner J. Chem. SOC.,Perkin Trans.2 1991 635. 30 A. R. Katritzky and M. Karelson J. Am. Chem. SOC.,1991 113 1561. 31 M. Karelson A. R. Katritzky and M. C. Zerner J. Org. Chem. 1991 56 134. 32 H. S. Rzepa and M. Yi J. Chem. SOC.,Perkin Trans. 2 1991 531. Theoretical Organic Chemistry 45 most reliable approach. A detailed analysis using discrete and continuum representa- tions of the effect of solvent on the Menshutkin reaction as modelled by the process NH3 + CH3Br -+ N+H3CH3+ shows the effects to be similar to other SN2 reactions but includes the following differences a decrease in the energy of activation is observed with an increase in solvent polarity and the transition state is found earlier along the reaction path showing the participation of solvent parameters in the reaction coordinate.The polarization of the solute by the RF created by solvent polarity increases the weight of charge transfer configurations with respect to the gas phase. Truhlar has developed a general parameterized SCF model for calculating free energies of solvation in aqueous sol~tion.~~,~~ Solvation terms are added to the AM1 Fock operator including reaction field polarization cavitation dispersion and hydrophobic effects through an empirical function of solvent accessible surface area. This has been termed the Solvation Model 1 and incorporated into the AMPAC package to produce AMSOL which is distributed through the quantum chemistry program exchange.36 Work on the theory of solvent effects on electronic spectra has been re~iewed.~’ An application to the spectra of conjugated molecules of an all atom solvent representation and a dipole shows the latter to be fast and reliable.The remaining examples in this section involve the use of MD Monte-Carlo (MC) and Brownian dynamics methods.39 A wide diversity of systems have been studied and the following list is by no means exhaustive free energy simulation analysis of the solvent effect on the anomeric equilibrium in D-glUCOSe;40 MD and FEP study of the protomeric equilibrium of 6-chloro-2-hydroxypyridine in the gas phase and solution;41 MC simulations of complex formation in imides and lac tarn^;^^ FEP study of the binding of pepstatin and its derivatives to rhizopus pepsin;43 Brownian dynamics simulation of base pair opening in DNA;44 role of solvent reorganization energies in the catalytic activity of enzymes;45 effects of salt on the structure and dynamics of the bis(penicil1amine) enkephalin ~witterion;~~ proton transfer in the formamidine and water system;47 FEP study of solvation in hydrazine and carbon tetra~hloride;~~ solvation of N-methylacetamide c~nformers.~~ 33 M.SolP A. Lledbs M. Duran J. Bertran and J. L. Abboud J. Am. Chem. SOC.,1991 113 2873. 34 C. J. Cramer and D. G. Truhlar J. Am. Chem. Soc. 1991 113 8305. 35 (a) C. J. Cramer and D. G. Truhlar J. Am. Chem. SOC.,1991 113 8552; (b) C. J. Cramer and D. G. Truhlar J. Am. Chem. Soc. 1991 113 9901. 36 AMSOL version 1 program 606 QCPE Indiana University Bloomington IN. 37 H. Ajgren and K.V. Mikkelsen J. MoL Struct. (THEOCHEM) 1991 234 425. 38 V. Luzhkow and A. Warshel J. Am. Chem. SOC.,1991 113 4491. 39 M. P. Allen and D. J. Tildesley Computer Simulation of Liquids Clarendon Oxford 1987. 40 S. Ha J. Gao B. Tidor J. W. Brady and M. Karplus J. Am. Chem. SOC.,1991 113 1553. 41 0. G. Parchment I. H. Hillier and D. V. S. Green J. Chem. SOC.,Perkin Trans. 2 1991 799. W. L. Jorgensen and D. L. Severance J. Am. Chem. Soc. 1991 113 209. B. G. Rao and U. C. Singh J. Am. Chem. SOC.,1991 113 6735. 42 43 44 F. Briki J. Ramstein R. Lavery and D. Genest J. Am. Chem. Soc. 1991 113 2490. 45 A. Yadov R. M. Jackson J. J. Holbrook and A. Warshel J. Am. Chem. SOC.,1991 113 4800. 46 P. E. Smith and B. M. Pettitt J.Am. Chem. SOC.,1991 113 6029. 47 M. Nagaoka Y. Okuno and T. Yamabe J. Am. Chem. SOC.,1991 113 769. 48 B. G. Rao and U. C. Singh J. Am. Chem. Soc. 1991 113 4381. 49 H.-A. Yu B. M. Pettitt and M. Karplus J. Am. Chem. SOC.,1991 113 2425. J. J. W. McDouall 5 Reactivity Pericyclic Reactions.-A study of a series of dissymmetric cyclohex-1,3-dienes react- ing with maleic anhydride and benzoquinone show a strong preference for addition to the carbonyl face of the dien~phile.~' In dimethyl acetylenedicarboxylate (DMAD) attack from this face decreases with successive methylidine substitution the opposite is true for N-phenyl-l,2,4-triazolinedione. In accounting for this in DMAD the unfavourable orbital interaction of closed shells of carbonyls and methylidines syn to the incoming T orbital of DMAD is thought to be important.Tetrafluoroethylene (TFE) does not undergo a Diels- Alder reaction. An explana- tion for this comes from calculations showing that the presence of fluorines does not have a strong influence on the Diels-Alder transition structure but does show a strong stabilization on diradical f~rrnation.~~ The 1,6diradical formed from TFE is 25 kcal mol-' more stable than that formed from ethylene. Hence TFE reacts with 1,3-butadiene to give 1,1,2,2,-tetrafluoro-3-vinyl-cyclobutane (9) via a diradical path. H FF-F Other interesting studies on Diels- Alder processes include a study of electron rich and electron deficient dienes in Diels- Alder cycloadditions with cyclic dienophile~,~~ and an investigation of the mechanism and site selectivity in the reaction between protoanemonin (5-methyl-2( 5H)-furanone) and b~tadiene.~~ The site specificity is rationalized through a highly asynchronous or two-step mechanism.The Cope rearrangement54 has been investigated using high level ab initio methods.55 Both a symmetrical aromatic transition state and a non-concerted path through an unsymmetrical transition state leading to a diradical intermediate have been located. From the energetics the authors conclude that reaction via both paths appears possible. Another high level treatment studies the formation of 1,3-cyclo- butanedione versus the 2s + 2A dimerization of ketene to diketene. Both products form through unsymmetrical transition states suggesting the reaction is non-synchronous but ~oncerted.~~ The barriers for the two processes differ by only 2 kcalmol-' with the formation of diketene being less favoured.Robb and co- worker~~~ have produced a CASSCF + MP2 study of the chemiluminescent decomposition of 1,2-dioxetanes including a valence bond analysis of the components of the wavefunction. so J. M. Coxon R. G. A. R. Maclagan D. Q. McDonald and P. J. Steel J. Org. Chem. 1991 56 2542. 51 S. J. Getty and W. T. Borden J. Am. Chem. SOC.,1991 113 4334. '* V. Branchadell M. Sodupe R. M. Ortufio A. Oliva D. Gomez-Pardo A. Guingant and J. d'Angelo J. Org. Chern. 1991 56 4135. 53 J. Orti R. M. Ortufio A. Oliva J. Font J. Bertran and J. J. Dannenberg J. Org. Chem.1991 56 2190. 54 W. T. Borden R. J. Loncharich and K. N. Houk Ann. Rev. Phys. Chem. 1988 39 213. 55 M. Dupuis C. Murray and E. R. Davidson J. Am. Chem. SOC.,1991 113 9756. 56 E. T. Seidl and H. F. Schaefer 111 J. Am. Chem. SOC.,1991 113 5195. 57 M. Ruguero F. Bernardi A. Bottoni M. Olivucci and M. A. Robb J. Am. Chem. Soc. 1991 113 1566. Theoretical Organic Chemistry Unsaturated Systems.-A detailed study at the AM1 level of theory of the reactions of ozone with ethylene and cis- and tr~ns-butadiene~~ finds support for the Criegee mechanism. This involves three distinct steps in which ozone and the olefin combine to give a cyclic adduct which then dissociates to a mixture of a carbonyl and a carbonyl oxide which recombine to form the ozonide.It is suggested that this process prevails in solution as well as in vacuo. The transition state geometries for radical additions to alkenesS9 show elec- trophilic nucleophilic and ambiphilic radicals to have a near constancy of the angle of attack (104°-1080) regardless of the nature of the radical. The relative stabiliz- ation of a carbon-carbon double bond by C1 and Br atoms is found to be greater for C1 by 1.3 kcal mol-1.60 This has consequences for the use of kBr/kcl ratios as mechanistic probes in vinylic substitution reactions. Comparison of biradical formation between enediyne (10) -P (1 1) and enyne- allene (12) + (13)61shows the latter to have a smaller activation barrier and a higher exothermicity. H H Singlet O2and triazolinedione (TAD) react with unsymmetrical cis-alkenes with regioselective double bond formation at the larger group.62 Results show that the rotational barriers do not control the selectivity of the ene reaction of singlet 0 and TAD with alkenes but that the regioselective ene product distribution depends on the free energies of activation of the isomeric transition states.SN2Reactions.-A systematic analysis of charge distribution at the transition state for the SN2 reactions63 (Scheme 1) for X = H NH, OH F CCH CN NC SH Nucl-+ CH,X + NuclCH + X-Scheme 1 58 M. J. S. Dewar J. C. Hwang and D. R. Kuhn J. Am. Chem. SOC.,1991 113 735. 59 H. Zipse J. He K. N. Houk and B. Giese J. Am. Chem. SOC.,1991 113 4324. 60 S. Hoz H. Basch J. L. Wolk Z. Rappaport and M.Goldberg J. Org. Chem. 1991 56 5424. 61 N. Koga and K. Morokuma J. Am. Chem. SOC.,1991 113 1907. 62 M. Stratakis Y. Elemes and F. Jensen J. Am. Chem. SOC.,1991 113 3180. 63 Z. Shi and R. J. Boyd J. Am. Chem. Soc. 1991 113 1072. 48 J. J. U? McDouall C1; Nucl = H and X = H NH2 OH F CN SH C1; Nucl = F shows that for some but not all reactions the charges on the nucleophile and the leaving group are the same. In such cases the assumption that the transition state occurs in the vicinity of the crossing of product-like and reactant-like diabatic surfaces holds. However in general the contributions of reactant and product wavefunctions are not equal in the transition state. With an electronegative nucleophile or leaving group charge development at the transition state is small.Intrinsic barriers have also been obtained64 and are found to be classifiable according to the hybridization of the leaving group and the electronic structure of the transition state. A detailed study of the classical SN2 reaction between chloride ion and methyl chloride including the effects of solvent,65 shows that the change in the internal energy of the reactants during the barrier climbing process involves three distinct regimes (i) vibrational activation of methyl chloride in the initial ion-dipole complex (ii) gradual increase in the kinetic and potential energies of the reactants (iii) fast dumping of reactant kinetic energy into the reactant potential energy resulting in reactants reaching the top of the potential energy barrier.The energy gained by the reactants comes primarily from solvent water. Many water molecules are involved in the process and almost as much energy is removed from the reactants as is deposited over the course of the barrier climb. The critical change in charge distribution occurs over a very short time and the total energy of the solvent molecules is almost constant. Oxygen Transfer.-In a study of the relative oxygen donor potential of dioxirane and its isomeric form carbonyl oxide it has been shown66 that reliable transition structures may only be located by geometry optimization at a correlated level of theory (MP2 being the lowest reliable method). To obtain accurate energies for these species higher order correlation effects must be considered including the contribution of triple substitutions.In the gas phase carbonyl oxide shows greater reactivity than dioxirane. Experimental work on substituted dioxiranes in solution shows the opposite trend. An investigation of the nature of the transition state for oxygen atom transfer from a hydroperoxide suggests that the accepted mechanism involving a direct displacement in concert with a 1,2 hydrogen shift must be modified to include the energetics of the 1,2-~hift.~~ The high barrier for the 1,2-shift can be dramatically lowered by the explicit inclusion of 1-2 molecules of solvent water. This yields a decrease of 20 kcal mol-' (relative to isolated reactants) or 10 kcal mol-' (relative to solvated reactants) per solvent molecule.This comes about by forming a cyclic transition structure allowing a 1,4-shift via a proton relay which bypasses the energetically demanding 1,2-shift. A high level ab initio study of the transition structure for the epoxidation of alkenes with peroxyacids6*" has provided a theoretical corroboration of the generally 64 Z. Shi and R. J. Boyd J. Am. Chem. SOC.,1991 113 2434. 65 B. J. Gertner R. M. Whitnell K. R. Wilson and J. T. Hynes J. Am. Chem. SOC.,1991 113 74. 66 R. D. Bach A. L. Owensby J. L. Andrks and H. B. Schlegel J. Am. Chem. SOC.,1991 113 7031. 67 R. D. Bach A. L. Owensby C. Gonzalez H. B. Schlegel and J. J. W. McDouall J. Am. Chem. SOC. 1991 113 6001. (a) R. D. Bach A. L. Owensby C. Gonzalez H. B. Schlegel and J.J. W. McDouall J. Am. Chem. SOC. 1991 113 2338; (b) P. D. Bartlett Rec. Chem. Bog. 1950 11 47. Theoretica1 Organic Chemistry accepted 'butterfly' mechanism proposed in 1950.6gb The electrophilicity of the peracid is attributed to the relatively weak 0-0 bond that is able to provide an empty (electrophilic) cr* orbital early along the reaction coordinate enabling mixing with the nucleophilic T bond of the alkene. General.-AMl MNDO and PM3 calculations of SN1dissociation pathways for N-benzylpyridinium cations69 (Scheme 2) predict that the unimolecular dissociation leads initially to ion-molecule complexes which in some cases are significantly lower in energy than the fully dissociated products. The calculations support an earlier suggestion of the existence of such intermediates made on the basis of experimentally determined activation volumes and of the behaviour of some of the cations toward nucleophilic reagents.R' ,>ffl' Tran Scheme 2 A study of the intrinsic reaction coordinate for the Grignard reaction Mg + C2H3X+ C,H3MgX (X = F C1) finds the activation barriers for C1 and F to be 29.7 kcal mol-' and 22.8 kcal mol-' respectively.'' Both reactions are exothermic by 54 kcal mol-'. The products have a linear C-Mg-X arrangement of Cs symmetry but arrive there via an unsymmetric path (Scheme 3). A similar study has been carried out for Mg insertion into the C-X bond of CH3Cl and CH3F.71 Scheme 3 In the activation of the C-H and C-C bonds by the transition metals iron cobalt nickel rhodium and palladium72 it is found that the barrier for C-C insertion is 14-20kcalmol-' higher than for C-H insertion.The size of the activation barrier is similar among metals in the same transition row but considerably lower for the second row. Other interesting studies include the protonation of 3-acetyltriazine and its rele- vance to the acid catalyzed decomposition of a~yltriazines;~~ the concerted or 69 A. R. Katritzky N. Malhorta G. P. Ford E. Anders and J. G. Tropsch J. Org. Chem. 1991 56 5039. 70 L. Liu and S. R. Davis J. Phys. Chem. 1991 95 8619. S. R. Davis J. Am. Chem. SOC., 71 1991 113 4145. 72 M. R. A. Blomberg P. E. M. Siegbahn U. Nagashima and J. Wennerberg J. Am. Chem. SOC.,1991 113 424. 73 J. L. Ozment A. M.Schiedekamp L. A. Schultz-Merkel R. H. Smith Jr. and C. J. Micheda J. Am. Chem. SOC.,1991 113 397. J. J. W. McDouall stepwise nature of nucleophilic addition to nitrile oxide^;'^ estimation of activation enthalpies for intramo!ecular hydrogen transfer as a function of the size of the cyclic transition state and CHC angle in reactions of a primary radical site with primary secondary and tertiary C-H bonds;75 the effect of hydration and dimerization of the formamidine rearrangement and modelling of proton transfer in nucleic acid bases;76 modes of ring opening in bicycle[ l.l.Olbut-2-yl radical and the relevance of orbital symmetry consideration^.^^ 74 M. T. Nguyen S. Malone A. F. Hegarty and I. H. Williams J. Org. Chem. 1991 56 3683. 75 X.L. Huang and J. J. Dannenberg J. Org. Chem. 1991,56 5421. 76 K. A. Nguyen M. S. Gordon and D. G. Truhlar J. Am. Chem. Soc. 1991 113 1596. 77 S. Olivella and A. SolC J. Am. Chem. SOC.,1991 113 83.