Controlling divergent hydrogen atom transfer in Vitamin B_12-photocatalyzed oxetane ring opening

Vitamin B₁₂ (VB₁₂), one of nature's most versatile cofactors, performs a multitude of radical and polar steps carefully choreographed by its surrounding enzyme microenvironment. It is highly desirable to capture this variegated reactivity in synthetic applications as well; however, few design principles for controlling VB₁₂ reactivity have been enumerated. Here we show proton availability to be a key factor in modulating VB₁₂ reactivity between hydrogen atom transfer (HAT) donation and hydrogen atom abstraction (HAA), with acidic, protic media favoring donation and aprotic media favoring abstraction. We demonstrate this principle in the modular transformation of oxetanes to saturated or allylic alcohols, depending on reaction media, via VB₁₂ photocatalysis. These reactions proceed with wide scope and high yield, and mechanistic experiments are consistent with our postulated mechanisms. Together, these results demonstrate rational tuning of VB₁₂ reactivity by controlling proticity of the reaction medium, and highlight the synthetic opportunities offered by divergent reactivity.