Steric and Stereoelectronic Control of the Mode Selectivity as a Function of Alkene Structure in the Reaction with Dimethyl α-Peroxy Lactone: Cycloadducts and Ene Products versus Epoxides

Abstract

The oxidation of di-, tri-, and tetrasubstituted alkenes 2 by dimethyl α-peroxy lactone (1) affords the cycloaddition, ene, and epoxidation products 3−6. In the presence of methanol, additionally the trapping products 7 are obtained. The observed dichotomy in the product distribution requires two different paths for this reaction, namely a path via an open, stretched 1,6 dipole and another path for epoxidation. Both paths arise from an SN2 attack of the double bond of the alkene 2 on the peroxide bond of the α-peroxy lactone 1, the first unsymmetrical (end-on attack), leading to the 1,6 dipole A, and the second symmetrical (central attack) with respect to the approach of the double bond, leading to epoxidation. The 1,6 dipole is postulated to afford the cycloadducts, of which the thermodynamically favored diastereomers are obtained, and the ene products. In the epoxidation, the α-lactone released after oxygen transfer oligomerizes to the polyester 8 or in the presence of methanol is trapped as α-methoxy acid 9. The reaction is regioselective both with respect to the attacked oxygen atom of the α-peroxy lactone 1, as revealed by the trapping products 7, as well as with respect to the attacking carbon atom for unsymmetrical alkenes 2c,d, as displayed by the ene products 5 and 6. The former regioselectivity is dictated by the inherent polarization of the peroxide bond through the carbonyl group which makes the alkoxy oxygen the more electrophilic one toward nucleophilic attack, while for the latter the incipient positive charge of the open 1,6 dipole is better stabilized by the more substituted carbon atom of the end-on attacking unsymmetrical alkene. The preferred reaction mode has been found to be sensitive to the structure of the alkene and the difference in reactivity has been explained in terms of steric and stereoelectronic factors. Thus, for the sterically less hindered cis-di- and trisubstitued alkenes the path along the open 1,6 dipole is favored (stereoelectronic control), while the more sterically demanding trans-di- and tetrasubstituted alkenes react by the epoxidation mode (steric control).