转自：康龙化成
Stereospecific Alkenylidene Homologation of Organoboronatesby SNV Reaction
Miao Chen†, Christian D. Knox‡, Mithun C. Madhusudhanan‡,Thomas H. Tugwell‡,Coco Liu†, Peng Liu‡* and Guangbin Dong†*
† Department of Chemistry, University ofChicago, Chicago, Illinois 60637, United States;
‡ Department of Chemistry, University ofPittsburgh, Pittsburgh, Pennsylvania, 15260, United States
—Nature, 2024, DOI:10.1038/s41586-024-07579-7.
Recommended by Xiuning Hu_MC4
ABSTRACT:Concertednucleophilic substitution, known as SN2reaction, is a fundamental organic transformation used in synthesis tointroduce new functional groups and construct carbon−carbon andcarbon−heteroatom bonds1. SN2 reactions typically involve backsideattack of a nucleophile to the σ* orbital of a C(sp3)−Xbond (X= halogen or other leaving group), resulting in complete inversion of a stereocenter. Incontrast, the corresponding stereoinvertive nucleophilic substitution on electronically unbiased sp2 vinyl electrophiles, namely concerted SNV(σ)reaction, ismuch rarer and so far, limited to carefully designed substrates mostly inring-forming processes. Here we show that concerted SNV reactions can be accelerated by aproposed strain-release mechanism in metallated complexes, leading to the development ofa general and stereospecific alkenylidenehomologation of diverse organoboronates.This method enables the iterative incorporation of multiple alkenylideneunits, giving cross-conjugated polyenes that are challenging to prepareotherwise. Further application to the synthesis of bioactive compoundscontaining multi-substituted alkenes is also demonstrated. Computationalstudies suggest an unusual SN2-like concerted pathway promoted bydiminishing steric strain in the square planar transition state, which explainsthe high efficiency and stereoinversivefeature of this metallate SNV reaction.
Backgroundand This Work
Substrate Scope
Synthetic Applications
Prof. Guangbin Dong and his co-workers have developed ageneral, efficient, and stereospecific alkenylidene homologation method, enabled by a distinct strain-release-enhanced metallate SNV mechanism. Thereaction tolerates various functional groups, as well as steric and electronicvariations in substrates. The excellent stereospecificity ofthis reaction makes it suitable for modular construction of tetrasubstituted alkenes, commonly found in complex bioactive compounds yet nontrivial toprepare efficiently. Iterative alkenylidenehomologation offers a route to the fully-substituted cross-conjugated polyenes,which are intriguing but hard-to-access structural motifs. The mechanisticinsights gained from the computational studies are expected to provide betterunderstandings of SNV reactions and further implications ondeveloping synthetically useful homologation methods.
