β-Boron or β-silicon effect enables a regioselective Ni-catalyzed hydrocyanation of internal alkynes

Abstract

Transition-metal-catalyzed hydrocyanation of alkynes offers a straightforward and atom-economic method to access alkenyl nitriles. However, achieving regio-control remains challenging, especially for unsymmetric di-alkyl substituted internal alkynes. In this study, we investigate the use of propargylic B(MIDA)s or silanes as substrates in a nickel-catalyzed hydrocyanation reaction. The reaction employs AIBN (2,2′-azobis(2-methylpropionitrile)) as a low-toxicity H–CN source and 1,4-dioxane or ethyl acetate as a green reaction solvent. The presence of β-boron or β-silicon groups induces a strong directing effect, favoring cyano group installation at the carbon adjacent to the boryl or silyl substituent. Mechanistic investigations reveal that this regioselectivity arises from the increased nucleophilicity of the γ-carbon and the protic nature of the hydrogen in the Ni–H complex. Additionally, a notable hyperconjugative σ(C–B) → σ*(C–Ni) interaction provides a thermodynamic driving force that further enhances regioselectivity. The resulting regio- and stereodefined products serve as versatile intermediates for the synthesis of a wide range of valuable molecules.