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 (DG8 < 0), with the antipodal net endergonic processes (DG8 > 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 !p 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 (l max = 402 nm) is disclosed. Whilst in the enzymatic process n O !p 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 !p C=O * interactions was confirmed by X-ray crystallography.

Phosphine-Catalyzed Z-Selective Carbofluorination of Alkynoates Bearing an N-Heteroarene Unit

“…4, 148.7, 144.9, 144.8, 137.5, 82.2, 81.0, 53.2. 132 (16), 131 (100), 104 (17), 78 (16), 77 (24), 53 (12), 52 ( 14), 44 (11). 1439 m, 1422 m, 1377 m, 1333 w, 1308 m, 1287 s, 1249 m, 1205 m, 1182 m, 1119 w, 1018 w, 1001 m, 949 w, 907 w, 834 s, 791 m, 769 s, 745 m, 712 w, 625 m, 575 m, 533 w, 477 w cm -1 .…”

“…10 We envisioned that the Z -selective synthesis of monofluoroalkenes would be feasible by selective E / Z isomerization driven by n→π* interactions. 11 This prompted us to examine whether this strategy could be applied to other pyridine derivatives and heterocyclic systems.…”

Intermolecular n→π* Interactions Based on a Tailored Multicarbonyl‐Containing Macrocycle

“…[2][3][4] Since the Raines group suggested the contribution of n!π* interaction associated with Bürgi-Dunitz trajectory to the conformational stability of collagen protein, [10,11] many efforts have dedicated to unveil the importance of n!π* interactions in proteins, [12][13][14][15][16][17][18] peptides and peptoids, [19][20][21][22] polymers, [23,24] small molecules, [25][26][27][28][29][30] and even reaction transition states. [31][32][33] On the other hand, manipulations of the intra-molecular n!π* interactions through molecular design to achieve conformational control, [34][35][36][37] engender photophysical properties, [38][39][40][41] tune supramolecular assembly, [42,43] modulate the reaction activity and selectivity [44][45][46] and influence dynamic covalent equilibria, [47,48] have also been investigated, though still relatively rare. So far, n!π* interactions as non-covalent driving force are currently limited to intramolecular systems.…”

Iron‐Catalyzed Positional and Geometrical Isomerization of Alkenes

“…Geometric isomerization allows to set the desired configuration of the carbon‐carbon double bond. The exergonic isomerization of ( Z )‐alkene to the thermodynamically more stable ( E )‐alkene is commonly encountered whereas the reversed endergonic pathway is far less studied and mainly reserved for photocatalysis [22–28] . Although 1,2‐disubstituted alkenes has been well‐exploited in stereoselective isomerization, tri‐ or tetra‐substituted alkenes have received considerably less emphasis.…”