Pyridine,
one of the most important azaarenes, is ubiquitous in
functional molecules. The electronic properties of pyridine have been
exploited to trigger asymmetric transformations of prochiral species
as a direct approach for accessing chiral pyridine derivatives. However,
the full potential of this synthetic strategy for the construction
of enantioenriched γ-functionalized pyridines remains untapped.
Here, we describe the first enantioselective addition of prochiral
radicals to vinylpyridines under cooperative photoredox and asymmetric
catalysis mediated by visible light. The enantioselective reductive
couplings of vinylpyridines with aldehydes, ketones, and imines were
achieved by employing a chiral Brønsted acid to activate the
reaction partners and provide stereocontrol via H-bonding interactions.
Valuable chiral γ-secondary/tertiary hydroxyl- and amino-substituted
pyridines were obtained in high yields with good to excellent enantioselectivities.
Transition-metal-catalyzed activations
of carbon–carbons
bonds of small strained rings have widespread applications in synthetic
and medicinal chemistry. However, coupling reactions of cyclobutanols
involving β-carbon elimination to construct C(sp3)–C(sp3) bonds have scarcely been developed. Here,
we demonstrate a highly enantioselective Pd-catalyzed intermolecular
C(sp3)–C(sp3) coupling reaction of a
broad range of cyclobutanol derivatives and unactivated alkenes, allowing
convenient access to a series of chiral benzene-fused cyclic compounds
in a highly regio-, chemo-, and enantioselective manner.
We report an enantioselective reductive cross coupling of electron-deficient olefins. Using a visible-light-driven cooperative photoredox and chiral Brønsted acid-catalyzed reaction with a Hantzsch ester as the terminal reductant, various cyclic and acyclic enones with 2-vinylpyridines were converted in high yields (up to 93%) to a wide range of enantioenriched pyridine derivatives featuring diverse γ-tertiary carbon stereocenters with good to excellent enantioselectivities (up to >99% ee).
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