How Dirhodium Catalysts Build Chiral Sulfur Centers: An Unexpected Mechanistic Blueprint from Kinetics, Spectroscopy, and Computation.

Chiral compounds comprising a stereogenic sulfur center are an important class of molecules. Recently, sulfenamides were alkylated using diazo compounds in the presence of chiral dirhodium catalysts. While this approach represents a milestone in generating chiral sulfilimines, the mechanism and stereodetermining step remain unclear. In the current work, we employ DFT to elucidate key mechanistic aspects of the catalytic cycle, which involve previously unknown intermediates and exhibit significant deviations from related carbene insertion reactions. The mechanism is corroborated using variable time normalization analysis (VTNA), ESI-HRMS, and UV-vis spectroscopy. Interestingly, while the sulfenamide attack onto the metallocarbene generates the chiral sulfur center, the reversibility of this step results in a subsequent step to be stereodetermining in nature. These results provide a revised mechanistic paradigm for sulfur stereocontrol in metal-carbene chemistry, offering general insights for the design of asymmetric transformations that form a chiral sulfur center.