1,3-Difunctionalization of Aminocyclopropanes via Dielectrophilic Intermediates

Abstract

We report an oxidative ring-opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3-dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O-acetal. Replacing the alkoxy group of the N,O-acetal can be achieved under acidic conditions through an elimination-addition pathway, while substitution of the halides by nucleophiles can be done under basic conditions through a S_N 2 pathway, generating a wide range of 1,3-difunctionalized propylamines. A proof of concept for asymmetric induction was realized using a chiral phosphoric acid (CPA) as catalyst, highlighting the potential of the method in enantioselective synthesis of important building blocks.

Keywords: 1,3-dielectrophile intermediate; amines; aminocyclopropanes; ring-opening; synthetic methodology.