Ni-Catalyzed Regio- and Enantioselective Domino Reductive Cyclization: One-Pot Synthesis of 2,3-Fused Cyclopentannulated Indolines

Transition-metal-catalytic domino
reactions represent important
advances in synthetic organic chemistry. Their development benefits
synthesis by providing highly efficient and step-economical methods
to complex molecules with impressive selectivity. Herein, a Ni-catalyzed
domino reductive cyclization of acrylamides with alkynyl bromides
is reported, enabling rapid assembly of a range of substituted 2,3-fused
cyclopentannulated indolines. Preliminary mechanistic studies revealed
that tricyclic indolines are afforded through a highly regioselective
migratory insertion of 1,3-diynes, which are formed from the homocoupling
of alkynyl bromides, into the in situ generated σ-alkyl-Ni­(II)
species, followed by nucleophilic addition of the resulting alkenyl
nickel to unactivated amides. Most importantly, a highly regio- and
enantioselective reductive cyclization of acrylamides and internal
alkynes has also been developed. This transformation takes place under
mild conditions with high efficiency, providing a rapid access to
structurally diverse cyclopentannulated indolines in synthetically
useful yields with high regioselectivity (>20/1) and enantioselectivity
(27 examples, 82–96% ee).