Report

High-turnover hypoiodite catalysis for asymmetric synthesis of tocopherols

Science  18 Jul 2014:
Vol. 345, Issue 6194, pp. 291-294
DOI: 10.1126/science.1254976

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Iodine blooms as an oxidation catalyst

Most catalysts for organic oxidation chemistry—whether biochemical or artificial—contain a transition metal like iron or palladium. Uyanik et al. now show that iodine can take the place of a metal in catalyzing efficient oxidative ring closures to make chromans—hexagonal rings incorporating oxygen that are perhaps best known as a constituent of the vitamin E structure (see the Perspective by Nachtsheim). The iodine is added as a salt with a chiral cation, which directs the reaction to form just one of two possible mirror-image variants of the product. Key to the success of the system was the addition of a base, which maintained the viability of an unstable, partially oxidized iodine intermediate critical to the reaction cycle. The results bode well for more general use of iodine salts as asymmetric oxidation-reduction catalysts.

Science, this issue p. 291; see also p. 270

Abstract

The diverse biological activities of tocopherols and their analogs have inspired considerable interest in the development of routes for their efficient asymmetric synthesis. Here, we report that chiral ammonium hypoiodite salts catalyze highly chemo- and enantioselective oxidative cyclization of γ-(2-hydroxyphenyl)ketones to 2-acyl chromans bearing a quaternary stereocenter, which serve as productive synthetic intermediates for tocopherols. Raman spectroscopic analysis of a solution of tetrabutylammonium iodide and tert-butyl hydroperoxide revealed the in situ generation of the hypoiodite salt as an unstable catalytic active species and triiodide salt as a stable inert species. A high-performance catalytic oxidation system (turnover number of ~200) has been achieved through reversible equilibration between hypoiodite and triiodide in the presence of potassium carbonate base. We anticipate that these findings will open further prospects for the development of high-turnover redox organocatalysis.

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