ChiralN-heterocycles are a common motif
in many
active pharmaceutical ingredients; however, their synthesis often
relies on the use of heavy metals. In recent years, several biocatalytic
approaches have emerged to reach enantiopurity. Here, we describe
the asymmetric synthesis of 2-substituted pyrrolidines and piperidines,
starting from commercially available ω-chloroketones by using
transaminases, which has not yet been comprehensively studied. Analytical
yields of up to 90% and enantiomeric excesses of up to >99.5% for
each enantiomer were achieved, which has not previously been shown
for bulky substituents. This biocatalytic approach was applied to
synthesize (R)-2-(p-chlorophenyl)pyrrolidine
on a 300 mg scale, affording 84% isolated yield, with >99.5%ee.