Mechanism of the Stereoselective α-Alkylation of Aldehydes Driven by the Photochemical Activity of Enamines

Herein we describe our efforts to elucidate the key mechanistic aspects of the previously reported enantioselective photochemical alpha-alkylation of aldehydes with electron-poor organic halides. The chemistry exploits the potential of chiral enamines, key organocatalytic intermediates in thermal asymmetric processes, to directly participate in the photo excitation of substrates either by forming a photoactive electron donor acceptor complex or by directly reaching an electronically excited state upon light absorption. These photochemical mechanisms generate radicals from closed shell precursors under mild conditions. At the same time, the ground-state chiral enamines provide effective stereochemical control over the enantioselective radical-trapping process. We use a combination of conventional photophysical investigations, nuclear magnetic resonance spectroscopy, and kinetic studies to gain a better understanding of the factors governing these enantioselective photochemical catalytic processes. Measurements of the quantum yield reveal that a radical chain mechanism is operative, while reaction-profile analysis and rate-order assessment indicate the trapping of the carbon-centered radical by the enamine, to form the carbon carbon bond, as rate-determining. Our kinetic studies unveil the existence of a delicate interplay between the light-triggered initiation step and the radical chain propagation manifold, both mediated by the chiral enamines.