The extension of racemization strategies
of dynamic kinetic resolution
in organic synthesis is a longstanding challenge, especially racemizing
two or more stereogenic centers simultaneously. Through the combination
of a palladium-catalyzed asymmetric allylic alkylation and a base-promoted
retro-oxa-Michael addition, a dynamic kinetic resolution of 2,3-disubstituted
flavonoids was achieved with up to 99% enantioselectivities, and two
contiguous stereocenters (including a quaternary stereogenic center)
were constructed simultaneously on the nucleophile flavonoids. The
key feature of the reaction was a base-promoted retro-oxa-Michael
addition for fast racemization of two stereogenic centers on the nucleophiles,
which can pave the way to developing asymmetric reactions of flavonoids
through dynamic kinetic resolution.
A ruthenium-catalyzed asymmetric
transfer hydrogenation of 2,3-disubstituted
flavanones was developed for the construction of three contiguous
stereocenters under basic conditions through a combination of dynamic
kinetic resolution and retro-oxa-Michael addition, giving chiral flavanols
with excellent enantioselectivities and diastereoselectivities. The
reaction proceeded via a base-catalyzed retro-oxa-Michael addition
to racemize two stereogenic centers simultaneously in concert with
a highly enantioselective ketone transfer hydrogenation step. The
asymmetric transfer hydrogenation could be achieved at gram scale
without loss of the activity and enantioselectivity.
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