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.