Visible-Light Induced “Photo-Click” Reactions of Acylsilanes with Pyruvate Electrophiles

Siloxycarbenes induced via the visible light irradiation of acylsilanes undergo highly efficient “photo-click” chemistry reactions with electron deficient ketones. This process requires no reagents other than visible light, proceeds with high efficiency and is tolerant of a wide range of functional groups. Pyruvate esters, thioesters, amides, nitriles and phosphonates were all suitable electrophiles including those tethered to complex drug or biomolecule scaffolds. The “photo-click” chemistry process was achieved on larger scale using both batch and flow methodologies, accompanied by diversification studies on the corresponding addition products. Mechanistic insights into siloxycarbene reactivity were also obtained by DFT analysis.