Origin of stereofacial selectivity in electrophilic additions to methylenecyclohexanes and methylenedioxanes. A theoretical and experimental study

Abstract

Addition reaction studies and ab initio calculations on methylenecyclohexane and 5-methylene-1,3dioxane systems suggest that two electronic factors contribute to the stereoselectivity of epoxidation and diimide reduction. These are respectively the spatial anisotropy of the HOMO with respect to the two faces of the double bond, common to both molecules, which is likely to be responsible for the overall axial stereofacial selectivity exhibited, and a similar anisotropy in the electrostatic potential field of the methylenedioxane caused by the oxygens; which also favours attack from an axial direction by polarisable electrophilic species. The anisotropy of the HOMO arises from the important topological difference between the contributions made to the HOMO by the periplanar C᎐H bonds and opposing C᎐O or C᎐C bonds. Catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and the dioxane systems and appears to be governed largely by steric effects. † There is some confusion here between the calculations of the Paquette group and those of Houk. Paquette speaks of a positively charged region, but talks of a charged electrophile being 'guided in' by the electron density, whereas Houk indicates that the predominant factor is a high electron density region, i.e. a negatively charged space on this side of the molecule. 11-13Paper 8/00999F

Photodriven Transfer Hydrogenation of Olefins

“…For dioxane 6g , diimide reduction occurred with excellent trans selectivity, in accord with the literature 18. The selectivity was attributed to the anisotropy effect induced by the oxygen atoms, as previously proposed.…”

Addition of electrophiles to unsymmetric alkenes. Effects of β oxygen substituents on the stereo- and regio-chemistry of positive halogen addition

“…For single step electrophilic additions to C᎐C double-bonds, we have already shown that the stereochemistry is profoundly influenced by the hyperconjugative interactions between the π system and a C᎐X bond situated β with respect to it. 1 We have here demonstrated that, for two step additions of positive halogen electrophiles, these same hyperconjugative effects, acting between an intermediate epihalonium ion and a β C᎐X bond, have a very significant influence on the regiochemistry of the process. Where X is more electronegative than hydrogen then, provided that the β C᎐X bond bears a fixed periplanar relation to the epihalonium ion, anti-Markownikoff addition is strongly promoted to the extent that it becomes exclusive when two such β C᎐X bonds are present.…”

“…In comparing this aspect of the positive halogen additions to 1 and 2, we note that the behaviour is similar to that observed with diimide, which reacts stereospecifically exo with 5methylenedioxanes, but almost unselectively towards methylenecyclohexane. 1 For the reaction of diimide, this was most satisfactorily accounted for by invoking the pronounced difference in electrostatic potential field between the two faces of the double bond which calculations had shown for 1. This difference gives a substantial bias for exo (axial) attack by an electrophile with an appreciable dipole, which, with the exception of bromine, is the case for the electrophiles that we have examined here.…”

“…Our recent investigation into the stereochemistry of the addition of electrophiles to 1,1-disubstituted alkenes such as the 5-methylenedioxane 1 and the methylenecyclohexane 2 has revealed that the hyperconjugative interaction of the correctly aligned β C᎐O, C᎐C and C᎐H bonds with the π system has a strong influence on the stereoreactivity of the system towards those electrophiles which add in a one step process. 1 We now report on the stereo-and, in particular, the regio-chemistry of additions to 1 and 2 of electrophiles which add in a two step manner.…”

“…Our previous results had suggested that such an influence might be strong. 1 In addition theoretical calculations carried out some time ago by Radom et al had predicted that a β C᎐O bond aligned with the p orbital of an adjacent carbocation would be poorer at stabilizing the cation hyperconjugatively than a β C᎐H or β C᎐C bond. 2 However, few experimental studies have unequivocally demonstrated this to be the case in practice.…”