Construction of Helical and Inherent Chirality by Brønsted Acid-Catalyzed Enantioselective Povarov Reaction of Alkynes

Povarov
reaction is an efficient methodology toward N-heterocycles.
Compared with the frequently investigated Povarov
reaction of alkenes, the catalytic enantioselective Povarov reaction
of alkynes remains challenging and has not been developed to date.
Herein, we report a chiral Brønsted acid-catalyzed enantioselective
Povarov reaction/oxidative aromatization of alkynes, providing a modular
platform for the preparation of quindoline- and indenopyridine-type
chiral helicenes with the simultaneous control of regioselectivity
and enantioselectivity. Both electron-rich ynamides and unpolarized
alkynes can undergo the transformation smoothly. Importantly, this
strategy could be further extended to the synthesis of inherently
chiral calix[4]arenes with effective enantiocontrol. Computational
studies reveal the reaction mechanism and origin of regio- and enantioselectivity.
Further derivatizations of chiral azahelicenes and investigations
into the photophysical and chiroptical properties demonstrate the
potential utility of this method. This protocol represents an important
advancement in the enantioselective Povarov reaction of alkynes, as
well as a rare example for the organocatalytic enantioselective transformation
of unpolarized alkynes.