Isotope effects and the nature of enantioselectivity in the shi epoxidation. The importance of asynchronicity.

The epoxidation of beta-methylstyrene catalyzed by the Shi fructose-derived ketone is studied using experimental kinetic isotope effects and DFT calculations. The observation of a large beta olefinic (13)C isotope effect and small alpha carbon isotope effect is indicative of an asynchronous transition state with more advanced formation of the C-O bond to the beta olefinic carbon. By varying the catalyst conformation and alkene orientation, diverse transition structure geometries were located calculationally, and the lowest-energy structure leads to an accurate prediction of the isotope effects. Given this support for the accuracy of the calculations employed, the nature of enantioselectivity in this and related epoxidations is considered. The lowest-energy transition structures are generally those in which the differential formation of the incipient C-O bonds, the "asynchronicity," resembles that of an unhindered model, and the imposition of greater or less asynchronicity leads to higher barriers. In reactions of cis-disubstituted and terminal alkenes using Shi's oxazolidinone catalyst, the asynchronicity of the epoxidation transition state leads to increased steric interaction with the oxazolidinone when a pi-conjugating substituent is distal to the oxazolidinone but decreased steric interaction when the pi-conjugating substituent is proximal to the oxazolidinone. Overall, the asynchronicity of the transition state must be considered carefully to understand the enantioselectivity.