Enantioconvergent Nucleophilic Substitution Reaction of Racemic Alkyne–Dicobalt Complex (Nicholas Reaction) Catalyzed by Chiral Brønsted Acid

Catalytic enantioselective syntheses
enable a practical approach
to enantioenriched molecules. While most of these syntheses have been
accomplished by reaction at the prochiral sp2-hybridized
carbon atom, little attention has been paid to enantioselective nucleophilic
substitution at the sp3-hybridized carbon atom. In particular,
substitution at the chiral sp3-hybridized carbon atom of
racemic electrophiles has been rarely exploited. To establish an unprecedented
enantioselective substitution reaction of racemic electrophiles, enantioconvergent
Nicholas reaction of an alkyne–dicobalt complex derived from
racemic propargylic alcohol was developed using a chiral phosphoric
acid catalyst. In the present enantioconvergent process, both enantiomers
of the racemic alcohol were transformed efficiently to a variety of
thioethers with high enantioselectivity. The key to achieving success
is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric
cationic intermediates generated via dehydroxylation of the starting
racemic alcohol under the influence of the chiral phosphoric acid
catalyst. The present fascinating DYKAT involves the efficient racemization
of these enantiomeric intermediates and effective resolution of these
enantiomers through utilization of the chiral conjugate base of the
phosphoric acid.