Origins of stereoselectivity in the chelation-controlled addition of alkyl radicals to α-methylene-γ-oxycarboxylic acid esters

Abstract

The diastereoselectivity in the chelation-controlled alkyl radical (R3˙) additions to α-methylene-γ-oxycarboxylic acid esters 1–12 was rationalised by analysing the low-energy conformers of radical intermediate models 46–59 and 66–69, which resemble the structures of early transition states of the exothermic transfer of a H-atom or allyl group. The sense of diastereoselectivity depends principally on the conformations of the sharply folded seven-membered chelate ring and the dihedral angle OC–O–C of the ester moiety. The transfer reaction to the radical intermediate bearing an ethoxy group with Z-geometry (dihedral angle ca. 0°) occurs predominantly on the exposed outside face of the radical centre, whereas the ethoxy group with E-geometry (dihedral angle ca. 180°) shields the outside face of the radical centre and lowers the diastereoselectivity. The diastereoselectivity depends also on the conformation of the CH2R3 group attached to the radical centre. When the CH2–R3 bond is perpendicular to the radical face, R3 shields the outside face of the radical centre. The intermediate bearing the ethoxy group with Z-geometry and the CH2–R3 bond parallel to the radical face affords the highest syn-selectivity in the reactions of γ-methoxymethoxy and γ-benzyloxy esters.