posted on 2022-01-28, 16:08authored bySubramanian Thiyagarajan, Raman Vijaya Sankar, Puthannur K. Anjalikrishna, Cherumuttathu H. Suresh, Chidambaram Gunanathan
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.