3724 J. Org. zyxwvutsr Chem. 1987,52, 3724-3738 sulfur and iodine is very stable but not between sulfur and fluorine, and such a bond is of marginal stability between sulfur and ch10rine.l~On this basis oxygen is not a prime candidate for 2c,3e interaction with an oxidized sulfur atom unless a suitable steric arrangement facilitates p-orbital overlap. This is in accord with our results which have identified rigid five- and six-membered cyclic structures zyxwvu as a necessary prerequisite for an observable sulfur-oxygen stabilization. Structure b takes into account that the unpaired electron could be subject to easy delocalization depending on suitably located energy levels in the MO diagram and may resemble radicals with u as well as with zyxwvu x character. An example which is probably best charac- terized by a three-center or perhaps better multicenter arrangement is found in the work of Perkins et al. on the photolysis of tert-buty12-(methylthio)peroxybenzoate.'g Steric demands are, however, probably high for such an aligned system. Localization of the unpaired electron at sulfur, finally, is another realistic alternative. This may occur in the form of a typical sulfuranyl radical as depicted in c or in a system with more Coulombic interaction d which may specifically be envisaged for the oxidized thioether acids. The latter appears reasonable in view of the electron delocalization in the carboxylate group. A crude ESR experiment on a y-irradiated sample of the endo-acid 5b in a Freon matrix at 77 K indicated g zyxwvuts - 2.03. This high value certainly points toward strong localization of the unpaired electron at sulfur. Generally, it is probably realistic to view a 4 as different geometric structures which may even exist in equilibrium. Which of these electronic situations prevails or describes best certain chemical properties will depend on structural parameters and substitution patterns. The nonspecific zyxwvu So-0 notation represents this. Conclusion From the results presented in this paper and some re- lated earlier investigations a number of general conclusions can be drawn, but also some questions are raised. Our data provide further supporting evidence for the concept of neighboring group p a r t i c i p a t i ~ n ~ ~ * ~ ~ , ~ ~ and, in fact, clearly establish it now for radical species. The oxidation of the sulfur function in our compounds as well as the properties of the resulting radical species have been demonstrated to depend significantly on the influence of functional groups. However, the latter have to be located in a position suitable for interaction with the sulfur. Acknowledgment. We are very thankful to Dr. M. J. Davies, for the ESR measurement, and to Professors T. F. Slater and R. L. Willson (all from Brunel University West-London) for providing the facilities for these ex- periments. K.-D.A. and S.M. gratefully acknowledge the support given by the Deutsche Forschungsgemeinschaft (DFG). R.S.G., M.H., and G.S.W. gratefully acknowledge support given by the US. Public Health Service, National Institutes of Health, Grant HL 15104. We also gratefully acknowledge support from NATO, Travel Grant RG85/ 0644. Registry No. 1, 13532-18-8; 2, 646-01-5; 3, 32391-97-2; 4, 111-17-1; 5a, 64887-94-1; 5b, 64887-93-0; 5c, 109216-48-0. (44) (a) Capon, B. zyxwvu Neighboring Group Participation; Plenum: New York, 1976; Vol 1. (b) Kirby, A. J. Adu. Phys. Org. Chem. 1980,17,183. (45) Jaffe, H.; Orchin, M. In Theory and Applications of Ultraviolet Spectroscopy; Wiley: New York, 1962; p 475. (46) Sweigart, D. A.; Turner, D. W. J. Am. Chem. SOC. 1972,94,5599. (47) Bock, H.; Wagner, G. Angew. Chem. 1972,84, 119. (48) Setzer, W. N.; Coleman, B. R.; Wilson, G. S.; Glass, R. S. Tetra- (49) Angyin, J. G.; Poirier, R. A.; Kucsman, A.; Csizmadia, I. G. zyx J. Am. (50) Alder, R. W.; Sessions, R. B.; Mellor, R. B.; Rawlins, J. M. J. (51) Alder, R. W.; Sessions, R. B. J. Am. Chem. SOC. 1978,101, 3651. (52) Nelsen, S. F.; Alder, R. W.; Sessions, R. B.; Asmus, K.-D.; Hiller, (53) Mohan, H.; Asmus, K.-D. J. Chem. Soc., Perkin Trans 2, in press. (54) Chaudhri, S. A.; Asmus, K.-D. Angew. Chem. 1981,93,690; An- (55) Clark, T. J. Comput. Chem. 1981,2, 261. hedron 1981,37, 2743. Chem. SOC. 1987,109, 2237. Chem. Soc., Chem. Commun. 1977,747. K.-0.; Gobl, M. J. Am. Chem. SOC. 1980,102, 1429. Mohan, H.; Asmus, K.-D. J. Am. Chem. SOC., in press. gew. Chem., Int. Ed. Engl. 1981,20,672. A General Treatment of Nucleophilic Chemistry+ Pascal Metivier, Alan J. Gushurst, and William L. Jorgensen* Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 Received March 4, 1987 A mechanistic model of nucleophilic chemistry has been developed and implemented in the computer program CAMEO. The program can make predictions on the outcome of nucleophilic processes by applying mechanistic reasoning and rules governing competing reactions that are based on literature precedents. The general procedure is divided into four steps: perception of reactive sites, recognition of applicable electron-pushmechanisms, evaluation of the mechanisms for each nucleophilic site, and overall analysis of competing pathways. The model and the chemical rules used in these steps are described in this paper. The approach has general utility for synthetic analyses and allows the program to make sophisticated predictions on the outcome of a great variety of nucleophilic reactions. I. Introduction CAMEO is an interactive computer program designed to predict the products of organic reactions given starting materials and reaction conditions. It arrives at its pre- dictions largely by mimicking the traditional mechanistic reasoning of chemists. The program is divided into modules which process different classes of reactions. These classes are distinguished primarily by the nature of the intermediates generated during the course of the reactions. They currently cover nu~leophilic,l-~ electrophilic?' rad- ' Computer-Assisted Mechanistic Evaluation of Organic Reactions. 13. 0022-326318711952-3724$01.50/0 0 1987 American Chemical Society