Palladium-Catalyzed Alkyne Hydrocyanation toward Ligand-Controlled Stereodivergent Synthesis of (E)- and (Z)-Trisubstituted Acrylonitriles

We herein describe a palladium-catalyzed hydrocyanation of propiolamides for the stereodivergent synthesis of trisubstituted acrylonitriles. This synthetic method tolerated various primary, secondary and tertiary propiolamides. The cautious selection of a suitable ligand is essential to the success of this stereodivergent process. Control experiments indicate the intermediacy of E-acrylonitriles, which lead to Z-acrylonitriles via isomerization. The density functional theory calculations suggests that the bidentate ligand L2 enables a feasible cyclometallation/isomerization pathway for the E to Z isomerization, while the monodentate ligand L1 inhibits the isomerization, leading to divergent stereoselectivity. The usefulness of this method can be demonstrated by the readily derivatization of products to give various E- and Z-trisubstituted alkenes. In addition, the E- and Z-acrylonitrile products have also been successfully employed in cycloaddition reactions.

Automated summary

A palladium-catalyzed hydrocyanation of propiolamides for the stereodivergent synthesis of trisubstituted acrylonitriles is described. The method can tolerate various primary, secondary, and tertiary propiolamides. The selection of a suitable ligand is crucial for the success of this stereodivergent process. Control experiments indicate the intermediacy of E-acrylonitriles, which undergo isomerization to form Z-acrylonitriles. Density functional theory calculations suggest that the bidentate ligand L2 enables a feasible cyclometallation/isomerization pathway for the E to Z isomerization, while the monodentate ligand L1 inhibits the isomerization, leading to divergent stereoselectivity. The usefulness of this method is demonstrated by the facile derivatization of products to give various E- and Z-trisubstituted alkenes. Additionally, the E- and Z-acrylonitrile products have been successfully employed in cycloaddition reactions.