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

Abstract

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.

Keywords: alkenes; bioinspired reactions; catalysis; isomerization; stereochemistry.

Figure 1

Top: The Z→E isomerization of maleate to fumarate enabled by maleate isomerase. Centre: The n_O→π_C=O* interaction in 1,4‐dicarbonyl derivatives. Bottom: An energy transfer platform for the E→Z isomerization where directionality is enabled by the n_O→π_C=O* interaction.

Figure 2

Exploring the substrate scope. Reactions were performed on a 0.3 mmol scale with 5 mol % of thioxanthone in 9 mL of acetonitrile and irradiated for 1 h with a 402 nm LED. The ratio of isomers in the photostationary state was determined by ¹H NMR spectroscopy. Yields are for the isolated Z isomer unless otherwise stated. The E‐designation of E ‐10 and E ‐22 reflects the higher priority of F than C.

Figure 3

Exploring the scope of ester–amide derivatives. Reactions were performed on a 0.3 mmol scale with 5 mol % of thioxanthone in 9 mL of acetonitrile and irradiated for 1 h with a 402 nm LED. The ratio of isomers in the photostationary state was determined by ¹H NMR spectroscopy. Yields are for the isolated product.

Figure 4

A) Comparison of triplet energy with the isomeric ratio in the photostationary state for dimethyl fumarate and fumaronitrile isomerization. B) Calculated triplet energies for substrates investigated in this study showing the same trend. C) Crystal structures of Z ‐14 and Z ‐32 showing key parameters together with depiction of their molecular orbitals obtained by NBO analysis (isovalue=0.035).

Figure 5

Crystal structures of Z ‐23 and Z ‐28 showing key angles.

Figure 6

Expanding the arsenal of stabilizing noncovalent interactions to facilitate contra‐thermodynamic alkene isomerization through selective energy transfer catalysis.