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Stereodivergent synthesis of 1,4-dicarbonyls by traceless charge–accelerated sulfonium rearrangement

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Science  17 Aug 2018:
Vol. 361, Issue 6403, pp. 664-667
DOI: 10.1126/science.aat5883

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Four varieties of carbonyl sandwich

Compounds with adjacent carbons sandwiched between two carbonyl (C=O) centers turn up frequently in organic chemistry. When these central carbons each have a substituent, there are four possible mutual geometries, all with potentially distinct biochemical properties. Kaldre et al. present a single method to access each stereoisomer individually. The outcome depends on the straightforwardly tunable configuration of a sulfoxide group in a precursor, which guides a rearrangement. The versatility of the method should facilitate selective access to 1,4-dicarbonyl motifs in pharmaceutical research.

Science, this issue p. 664

Abstract

The chemistry of the carbonyl group is essential to modern organic synthesis. The preparation of substituted, enantioenriched 1,3- or 1,5-dicarbonyls is well developed, as their disconnection naturally follows from the intrinsic polarity of the carbonyl group. By contrast, a general enantioselective access to quaternary stereocenters in acyclic 1,4-dicarbonyl systems remains an unresolved problem, despite the tremendous importance of 2,3-substituted 1,4-dicarbonyl motifs in natural products and drug scaffolds. Here we present a broad enantioselective and stereodivergent strategy to access acyclic, polysubstituted 1,4-dicarbonyls via acid-catalyzed [3,3]-sulfonium rearrangement starting from vinyl sulfoxides and ynamides. The stereochemistry at sulfur governs the absolute sense of chiral induction, whereas the double bond geometry dictates the relative configuration of the final products.

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