Light-driven reductive cyclization catalyzed by vitamin B₁₂-based artificial photoenzymes

In Nature, metabolically active vitamin B₁₂ possesses an unusual metal-carbon bond that can be readily cleaved under visible light. This photolytic mechanism is crucial for B₁₂-dependent photoreceptors in regulating the gene expression in microbes, but no enzymes have been identified so far that exploit the unique photoreactivity of cobalamin. Here, we present the assembly of cobalamin-serum albumin conjugates and demonstrate their use as artificial photoenzymes to catalyze the intramolecular cyclization of unactivated alkyl halides with tethered alkenes. The encapsulation of cobalamin within a protein environment enables the reaction to occur with 4.5 × enhanced reactivity for the model substrate. A range of alkyl halides were successfully cyclized under the developed conditions to produce various molecular scaffolds and a tandem Giese reaction with methyl acrylate was also demonstrated.