Stereospecific alkenylidene homologation of organoboronates by S N V reaction.

Concerted nucleophilic substitution, known as S N 2 reaction, is a fundamental organic transformation used in synthesis to introduce new functional groups and construct carbon-carbon and carbon-heteroatom bonds 1 . S N 2 reactions typically involve backside attack of a nucleophile to the σ* orbital of a C(sp 3 )-X bond (X= halogen or other leaving group), resulting in complete inversion of a stereocenter 2 . In contrast, the corresponding stereoinvertive nucleophilic substitution on electronically unbiased sp 2 vinyl electrophiles, namely concerted S N V(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 N V 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 N 2-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 N V reaction.