DNA Compatible Intermolecular Wittig Olefination for the Construction of α, β-Unsaturated Carbonyl Compounds

Abstract

A robust DNA-compatible Wittig reaction mediated by PPh₂CH₃ has been validated for DNA-conjugated α-chloroacetamides with aldehydes and, alternatively, DNA-conjugated aldehydes with α-halo acetamides or ketones. Further, 2-aminopyridines were acylated with α-chloroacetyl chloride and then reacted with DNA-conjugated aldehydes. Lastly, a pilot library employing our optimized Wittig reaction protocol was synthesized. The ability to generate <i>α,β</i>-unsaturated carbonyl compounds may be particularly useful for the design of DNA-encoded libraries capable of covalently interacting with protein targets.