Alcohols and nitrile functionalities have widespread applications in biochemical and chemical synthesis. Catalytic transformations involving C–C bond formation relying on unsaturated coupling partners create important pathways for processes in synthetic, material, and medicinal chemistry. The discovery of a simple and selective coupling of nitriles with allylic alcohols catalyzed by a ruthenium pincer complex is described, which tolerates reactive functional groups such as carbamate, sulfonate, olefin, cyano, and trifluoromethyl-substituted benzyl nitriles. Homo allylic alcohols also provided 1,4-addition products following the isomerization of double bonds. Mechanistic studies supported that the allylic alcohols initially undergo selective oxidation by the catalyst to α,β-unsaturated carbonyl compounds followed by 1,4-conjugate addition of benzyl nitriles catalyzed by a base and subsequent catalytic reduction of carbonyl functionality, leading to the formation of δ-hydroxynitrile products. The catalytic cycle of this tandem process is established by density functional theory studies. Remarkably, anipamil drug is successfully synthesized using this catalytic protocol. The utility of the δ-hydroxynitrile products in the synthesis of biologically active molecules and their further functionalization are also demonstrated. 

Catalytic Formal Conjugate Addition: Direct Synthesis of δ-Hydroxynitriles from Nitriles and Allylic Alcohols

Ruthenium Complex-Catalyzed Tandem Reactions of Alcohols with Acetonitriles for Synthesis of α-Substituted Amides

[Cp*IrCl2]2 with a phosphine-free ligand α,α,α-terpyridine shows high catalytic performance in chemodivergent synthesis of α-alkylated arylacetonitriles in the presence of K2CO3 and α-alkylated acetamides in the presence of tBuOK, respectively.

Yuan-Rui Qiu

Papers

Base-controlled chemoselectivity: direct coupling of alcohols and acetonitriles to synthesise α-alkylated arylacetonitriles or acetamides