posted on 2023-12-01, 15:40authored bySong Li, Xigong Liu, Chen-Ho Tung, Lei Liu
Catalytic asymmetric preparation of chiral 3-monosubstituted
oxindoles
represents a significant challenge in synthetic chemistry due to the
ease of racemization of the tertiary stereocenter through enolization.
Here, we describe a general titanium-catalyzed chemo- and enantioselective
indole oxidation to produce a diverse set of chiral 3-monosubstituted
oxindoles with up to 96% yield, 99% ee, and with a substrate/catalyst
ratio of 10,000 by using the combination of a simple titanium(salan)
catalyst with green and atom-economic terminal oxidant H2O2. The mild approach tolerates a broad range of functional
groups, enabling late-stage asymmetric diversification of a series
of commercial drugs and natural products together with late-stage
asymmetric construction of a wide set of enzyme antagonists, all of
which are difficult to achieve through existing methods.