Bio-Inspired Deconjugative Isomerization of Borylated Dienoates

The evolutionary success of (poly)ene isomerization paradigms in generating molecular diversity is manifest throughout biosynthesis. Algorithms to relocate short π-systems, often against a thermochemical bias, with simultaneous regio- and stereo-control are a feat of precision that remain challenging to translate to a laboratory setting. The divergent biosynthesis of vitamin D and tachysterol from pre-vitamin D, leveraging positional or geometric isomerization, is a powerful exemplar. Inspired by this venerable blueprint, a deconjugative isomerization of borylated dienoates has been developed under the auspices of photochemical activation. Alleviating ground-state thermochemical restrictions through light-induced reactivity enables facile bifurcation of the diene and carbonyl chromophores: this occurs by a sequential geometric isomerization / [1,5]-hydrogen shift sequence that emulates pre-vitamin D photobiology. Broad functional group tolerance is observed, allowing the process to be leveraged in complex settings that would otherwise require multi-step approaches. It is envisaged that the operationally simple, enabling nature of this strategy, coupled with the traceless nature of the boron handle, will stimulate interest in poly(ene) relocation strategies and begin to reconcile the paucity of synthetic methods with their ubiquity in biosynthesis.