Forming Stereogenic Centers in Acyclic Systems from Alkynes

Abstract

The combined carbometalation/zinc homologation followed by reactions with α-heterosubstituted aldehydes and imines proceed through a chair-like transition structure with the substituent of the incoming aldehyde residue preferentially occupying a pseudo-axial position to avoid the two gauche interactions. The heteroatom in the axial position produces a chelated intermediate (and not a Cornforth-Evans transition structure for α-chloro aldehydes and imines) leading to a face differentiation in the allylation reaction. This method provides access to functionalized products in which three new carbon-carbon bonds and two to three stereogenic centers, including a quaternary one, were created in acyclic systems in a single-pot operation from simple alkynes. All-carbon quaternary stereocenter: The combined carbometalation/zinc homologation of alkynes followed by reactions with α-heterosubstituted aldehydes and imines provides access to functionalized acyclic adducts. These adducts obtained in a single-pot reaction have three new carbon-carbon bonds and two to three stereogenic centers, including a quaternary carbon stereocenter.