Heteroatom-directed lithiations of chiral aklyl carbamates: A powerful tool for enantioselective synthesis

Abstract

Chiral alkyl carbamates, bearing hetero-substituents in the β- or γ-position, are deprotonated by sec-butyllithium/TMEDA with efficient selection between the diastereotopic α-methylene protons. Depending on the substitution pattern and the reaction conditions, either steric or chelate effects act as stereodirecting devices. In several cases, this substrate-induced stereoselectivity is enhanced or is overridden by means of sec-butyllithium/(-)-sparteine, which exhibits a strong preference for the abstraction of the pro-S proton. Altogether, an efficient and simple protocol for the stereoselective generation of synthetic equivalents for hetero-substituted α-oxyalkanide synthons is presented.