Chemistry

Calcium Catalysis

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Science  04 Mar 2011:
Vol. 331, Issue 6021, pp. 1114
DOI: 10.1126/science.331.6021.1114-a

Synthetic asymmetric catalysts have traditionally comprised transition metals bearing chiral ligands, though over the past decade, free amines, phosphate diesters, and urea derivatives have emerged as increasingly effective alternatives. The phosphate class of organocatalysts tends to rely on ion pair formation between a protonated substrate and a residual phosphate anion bearing a chiral, often polycyclic aromatic carbon framework. Zheng et al. were exploring the application of this type of catalyst toward asymmetric chlorination of phenyloxindoles, and they found that a particular phosphate diester afforded high enantioselectivity just after purification by silica gel chromatography, yet minimal selectivity after an acid wash. This result led them to screen phosphate salts with a variety of cations, culminating in the discovery that calcium—a biochemically critical ion that has found comparatively few applications in synthetic catalysis—proved the optimal counterion for conferring selectivity. Though the mechanism remains unclear, the authors posit possible activation of the chlorine source (N-chlorosuccinimide) by calcium coordination, concomitant with oxindole activation by the phosphate. Phenyloxindoles with a range of substitution patterns were chlorinated in nearly quantitative yields within half an hour at room temperature, with enantioselectivities generally exceeding 90%.

J. Am. Chem. Soc. 133, 10.1021/ja109824x (2011).

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