Base-Activated Latent Heteroaromatic Sulfinates as Nucleophilic Coupling Partners in Palladium-Catalyzed Cross-Coupling Reactions

Abstract

Heteroaromatic sulfinates are effective nucleophilic reagents in Pd⁰ -catalyzed cross-coupling reactions with aryl halides. However, metal sulfinate salts can be challenging to purify, solubilize in reaction media, and are not tolerant to multi-step transformations. Here we introduce base-activated, latent sulfinate reagents: β-nitrile and β-ester sulfones. We show that under the cross-coupling conditions, these species generate the sulfinate salt in situ, which then undergo efficient palladium-catalyzed desulfinative cross-coupling with (hetero)aryl bromides to deliver a broad range of biaryls. These latent sulfinate reagents have proven to be stable through multi-step substrate elaboration, and amenable to scale-up.

Keywords: cross-coupling; desulfination; palladium; pyridine; sulfone.