Choice of Phenyls

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Science  06 Jun 2008:
Vol. 320, Issue 5881, pp. 1262
DOI: 10.1126/science.320.5881.1262c

The formation of carbon-carbon bonds in the synthesis of organic compounds has become relatively straightforward when the sites being coupled are respectively substituted with an electronegative halide and an electropositive boron or tin moiety. The drawback of this approach is the necessity of appending these reactive groups to a precursor skeleton that consists predominantly of C-H bonds. The past decade has seen substantial progress in direct catalytic activation of C-H bonds, in certain cases eliminating the need for either the halide, the boronate, or both. One remaining hurdle is the achievement of enantioselectivity across a wide range of substrates. Shi et al. present progress in this vein with a chiral palladium catalyst that selectively couples a boron-substituted alkyl group to one of two phenyl rings bound to a central carbon, thereby desymmetrizing the compound. The carbon center also bears a pyridine group to direct the catalyst orientation by coordination to the Pd center. Successive trial experiments revealed that the amino acid leucine N-substituted with a menthyl ester proved the most effective ligand, resulting in high yields and enantiomeric excesses as high as 95%. Preliminary studies with a different ligand—an amino acid substituted with a bulky cyclopropyl group— also induced asymmetric coupling to one of the methyl groups in isopropyl pyridine, supporting the potential of this approach for sp3 as well as sp2 C-H site activation. — JSY

Angew. Chem. Int. Ed. 47, 10.1002/anie.200801030 (2008).

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