Fluxional Cyclic Seleninate Ester: NMR and Computational Studies, Glutathione Peroxidase-like Behavior, and Unexpected Rearrangement

• Published in: Journal of organic chemistry Vol. 78; no. 20; pp. 10369 - 10382
• Main Authors: McNeil, Nicole M. R, Matz, Marie C, Back, Thomas G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-10-2013
• Subjects: Benzyl Compounds - chemistry; Catalysis; Glutathione Peroxidase - chemistry; Glutathione Peroxidase - metabolism; Hydrogen Peroxide - chemistry; Magnetic Resonance Spectroscopy; Molecular Structure; Organoselenium Compounds - chemistry; Oxidation-Reduction; Sulfhydryl Compounds - chemistry; Sulfides - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo401757m

The oxidation of allyl selenide 12 with hydrogen peroxide produced the corresponding allyl selenurane 14, the cyclic seleninate ester 4, or the rearranged O-allyl seleninate ester 18, dependng on the conditions. Crossover experiments with selenide 12 and its deuterated crotyl analogue 27 indicated an intramolecular rearrangement that proceeds by an intramolecular pathway where the allyl or crotyl group is translocated via its distal carbon atom to the hydroxy­methyl functionality. Variable-temperature NMR experiments with cyclic seleninate ester 4 revealed fluxional behavior at room temperature that was catalyzed by trifluoro­acetic acid. Computational studies indicated an activation energy of 12.3 kcal mol–1 for hydroxyl interchange at selenium, comparable to the value of 15.5 kcal mol–1 derived from the NMR experiments. The glutathione peroxidase-like activity of 4 was measured in an assay where the catalysis of the reduction of hydrogen peroxide with benzyl thiol was monitored by the appearance of dibenzyl disulfide. The catalytic activity of 4 was double that observed with the unsubstituted seleninate ester 2 but was limited by the competing accumulation of the relatively inert selenenyl sulfide 32, resulting in a deactivation pathway that competes with the primary catalytic cycle.