Stereospecific alkenylidene homologation of organoboronates by S_NV reaction.

Abstract

Concerted nucleophilic substitution, known as S_N2 reaction, is a fundamental organic transformation used in synthesis to introduce new functional groups and construct carbon-carbon and carbon-heteroatom bonds¹. S_N2 reactions typically involve backside attack of a nucleophile to the σ* orbital of a C(sp³)-X bond (X = halogen or other leaving group), resulting in complete inversion of a stereocentre². By contrast, the corresponding stereoinvertive nucleophilic substitution on electronically unbiased sp² vinyl electrophiles, namely concerted S_NV(σ) reaction, is much rarer, and so far limited to carefully designed substrates mostly in ring-forming processes^3,4. Here we show that concerted S_NV reactions can be accelerated by a proposed strain-release mechanism in metallated complexes, leading to the development of a general and stereospecific alkenylidene homologation of diverse organoboronates. This method enables the iterative incorporation of multiple alkenylidene units, giving cross-conjugated polyenes that are challenging to prepare otherwise. Further application to the synthesis of bioactive compounds containing multi-substituted alkenes is also demonstrated. Computational studies suggest an unusual S_N2-like concerted pathway promoted by diminishing steric strain in the square planar transition state, which explains the high efficiency and stereoinversive feature of this metallate S_NV reaction.