Enantiocomplementary Access to Silicon-Stereogenic Silacyclohexenones via Ene-Reductase-Catalyzed Desymmetrization of Silacyclohexadienones

Silicon-stereogenic organosilicon compounds have garnered
ever-increasing
attention and found widespread applications in various areas as functional
molecules. The biocatalytic synthesis of these entities has been scarcely
reported and is limited to the use of hydrolases, which suffer from
low yields and insufficient stereoselectivities. Herein, we report
an unprecedented non-hydrolase-type enzyme-catalyzed synthesis of
silicon-stereogenic organosilicon compounds. Enantiocomplementary
reduction of a diverse array of silacyclohexadienones through the
ene-reductase-catalyzed desymmetrization process was accomplished,
providing silicon-stereogenic silacyclohexenones with γ,γ-disubstitution
in high conversions (up to 99%) and isolated yields (up to 88%), along
with superb enantioselectivities (mostly ≥97% ee). The observed
carbon–silicon switch effects, specifically the reversed enantioselectivity
and enhanced reactivity, could likely be attributed to the unique
stereoelectronic features of silicon. Molecular dynamics (MD) simulations
were conducted to shed light on the origins of the complementary enantioselectivities
displayed by different ene-reductases. This study not only offers
expedited and enantiocomplementary access to chiral γ,γ-disubstituted
silacyclohexenones but also showcases the utility and immense potential
of enzyme catalysis in the construction of valuable silicon-stereogenic
organosilanes.