A convenient synthesis of enantioenriched α-haloaldehydes

Abstract

α-Haloaldehydes represent an important family of chiral building blocks that are particularly well suited for the synthesis of sp³-rich heterocycles and polyketide-derived natural products. While the organocatalytic and enantioselective preparation of α-haloaldehydes has been well-developed, challenges with their purification and stability often complicate their use. Here, we describe a convenient procedure for the enantioselective preparation of R- or S-configured α-haloaldehydes involving the oxidative cleavage of readily prepared, stable and storable halohydrin aldol products. This operationally simple, two-step process affords α-haloaldehydes in high chemical and enantiomeric purity with minimal manipulation required. This method for preparing α-haloaldehydes should improve their accessibility and inspire new uses in complex molecule synthesis.