Leveraging the n→π* Interaction in Alkene Isomerization by Selective Energy Transfer Catalysis

Examples of geometric alkene isomerization in nature are often limited to the net exergonic direction (ΔG°<0), with the antipodal net endergonic processes (ΔG°>0) comparatively under‐represented. Inspired by the expansiveness of the maleate to fumarate (Z→E) isomerization in biochemistry, we investigated the inverse E→Z variant to validate n(O)→π(C=O)* interactions as a driving force for contra‐thermodynamic isomerization. A general protocol involving selective energy transfer catalysis with inexpensive thioxanthone as a sensitizer (λ (max)=402 nm) is disclosed. Whilst in the enzymatic process n(O)→π(C=O)* interactions commonly manifest themselves in the substrate, these same interactions are shown to underpin directionality in the antipodal reaction by shortening the product alkene chromophore. The process was validated with diverse fumarate derivatives (>30 examples, up to Z:E>99:1), including the first examples of tetrasubstituted alkenes, and the involvement of n(O)→π(C=O)* interactions was confirmed by X‐ray crystallography.