Catalytic
stereoselective desymmetrization of prochiral compounds
to valuable chiral molecules is of interest in asymmetric synthesis.
Here, we report the development of an efficient biocatalytic desymmetrization
strategy for the stereodivergent synthesis of various chiral epoxides
and oxazolidinones by the identification and engineering of halohydrin
dehalogenases. The use of stereocomplementary halohydrin dehalogenases
for the desymmetrization of 2-substituted-1,3-dichloro-2-propanols
generates chiral epoxides in up to 95% yield and 99% ee by a single-step dehalogenation reaction, as well as chiral oxazolidinones
in up to 88% yield and >99% ee via a dehalogenation
and cyanate-mediated epoxide ring-opening cascade reaction. We also
propose a probable mechanism for stereoselectivity control in the
halohydrin dehalogenase-catalyzed desymmetrization reaction.
A new
method for the ex situ generation of difluorodiazoethane
(CF2HCHN2) and a procedure for its efficient
use in [3 + 2] cycloaddition with nitroolefins by the AcOH/O2 catalyst system were developed by using a simple two-chamber system.
The method provides a facile and straightforward access to a series
of 4-substituted 5-difluoromethyl-3-nitro-1H-pyrazoles
that are of interest in medicinal chemistry. Interestingly, the key
factor for the success of this method is the efficient preparation
of CF2HCHN2 by an ex situ process.
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