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

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 S(N)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.

Automated summary

The chemoselective activation of Tsuji's 2-(cyanomethyl)allyl carbonates to generate palladium-trimethylenemethane 1,3-dipoles can be realized in the presence of Morita-Baylis-Hillman carbonates from activated ketones. The subsequent cascade annulations lead to the formation of complex frameworks with good to excellent enantioselectivity, while a similar annulation sequence using benzoyl aldehyde-derived substrates produces fused cyclopenta[b]furan architectures.