A Double Deprotonation Strategy for Cascade Annulations of Palladium-Trimethylenemethanes and Morita-Baylis-Hillman Carbonates to Construct Bicyclo[3.1.0]hexane Frameworks

Angew Chem Int Ed Engl. 2021 Jun 14;60(25):13913-13917. doi: 10.1002/anie.202102842. Epub 2021 May 11.

Abstract

Here we report that the chemoselective activation of Tsuji's 2-(cyanomethyl)allyl carbonates to generate the palladium-trimethylenemethane 1,3-dipoles via a deprotonation strategy can be realized in the presence of Morita-Baylis-Hillman carbonates from substantial activated ketones. The following SN 2'-addition enables the formation of new 1,3-dipole species having an activated alkene moiety through a second deprotonation process, which then undergo cascade [1+2]/[3+2] annulations to furnish complex bicyclic [3.1.0]hexane frameworks having three contiguous quaternary stereogenic centers with good to excellent enantioselectivity. Moreover, by using benzoyl aldehyde-derived substrates, a [1+4]/[3+2] annulation sequence is similarly developed to produce fused cyclopenta[b]furan architectures.

Keywords: bicyclo[3.1.0]hexane; cascade annualtions; chemoselectivity; double deprotonation strategy; palladium-trimethylenemethane.

Publication types

  • Research Support, Non-U.S. Gov't