Reductant-Free Cross-Electrophile Synthesis of Di(hetero)arylmethanes by Palladium-Catalyzed Desulfinative C-C Coupling.

An efficient Pd-catalyzed one-pot desulfinative cross-coupling to access medicinally relevant di(hetero)arylmethanes is reported. The method is reductant-free, and involves a sulfinate transfer reagent and a Pd-catalyst mediating the union of two electrophilic coupling partners; a (hetero)aryl halide and a benzyl halide. We establish for the first time that benzyl sulfinates, generated in situ, undergo efficient Pd-catalyzed desulfinative cross-coupling with (hetero)aryl halides to generate di(hetero)arylmethanes. The reaction can be extended to benzylic pseudohalides derived from benzyl alcohols. The reactions are straightforward to perform and scalable, and all reaction components are commercially available.

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

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: ß-nitrile and ß-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.

Copper-Catalyzed Synthesis of Masked (Hetero)Aryl Sulfinates.

Catalysis using substoichiometric copper facilitates the synthesis of masked (hetero)aryl sulfinates under mild, base-free conditions from aryl iodides and the commercial sulfonylation reagent sodium 1-methyl 3-sulfinopropanoate (SMOPS). The development of a tert-butyl ester variant of the SMOPS reagent allowed the use of aryl bromide substrates. The sulfones thus generated can be unmasked and functionalized in situ to form a variety of sulfonyl-containing functional groups.