Catalytic Asymmetric Construction of Si-Chiral Silabicyclo[3.3.1]Nonanes Using Functionalized Prochiral Silacyclohexanones

The development of chiral three-dimensional, sp³-rich architectures to facilitate the discovery of potent functional molecules is at the forefront of synthetic chemistry. However, facile synthesis of saturated and bridged Si-chiral silacycles remains elusive due to a lack of pluripotent Si-prochiral platforms capable of diversity-oriented asymmetric synthesis. Herein, we report the invention of functionalized prochiral 4,4-disubstituted silacyclohexanones (FPDSs) as platforms for the modular synthesis of multifunctional sp³-rich Si-chiral sila-bicyclo[3.3.1]nonanes. The FPDS platforms are readily accessible via a newly established tandem S_N2‑substitution/Krapcho‑decarboxylation sequence as a key step to silacyclohexanone core. The utility of FPDS is demonstrated in catalytic asymmetric synthesis of diverse Si-chiral sila-bicyclo[3.3.1]nonanes via desymmetric intramolecular aldol reaction, tandem imine formation/Mannich, or Wittig/Michael sequence by chiral enamine catalysis, as well as α-arylation by cooperative chiral enamine/palladium catalysis. Notably, this represents the first stereoselective method to produce functionalized sp³-rich Si-chiral bridged silacycles and the first asymmetric organo/metal cooperative catalysis for forging Si-chirality.