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. 2010 Aug 18;132(32):11027-9.
doi: 10.1021/ja105148g.

Asymmetric Suzuki cross-couplings of activated secondary alkyl electrophiles: arylations of racemic alpha-chloroamides

Pamela M Lundin  1 , Gregory C Fu
Affiliations

Asymmetric Suzuki cross-couplings of activated secondary alkyl electrophiles: arylations of racemic alpha-chloroamides

Pamela M Lundin et al. J Am Chem Soc. .

Abstract

A nickel-catalyzed stereoconvergent method for the enantioselective Suzuki arylation of racemic alpha-chloroamides has been developed. This process provides a unique example of an asymmetric arylation of an alpha-haloamide, an enantioselective arylation of an alpha-chlorocarbonyl compound, and an asymmetric Suzuki reaction with an activated alkyl electrophile or an arylboron reagent. The method is also applicable to the corresponding enantioselective cross-coupling of alpha-bromoamides. The coupling products can be transformed without racemization into enantioenriched alpha-arylcarboxylic acids and primary alcohols. A modest kinetic resolution of the alpha-chloroamide was observed; a mechanistic study indicated that the selectivity may reflect discrimination by the chiral catalyst of the two enantiomeric alpha-chloroamides in an irreversible oxidative-addition process.

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References

    1. For leading references to the pharmacology of this family of compounds, see: Landoni MF, Soraci A. Current Drug Metabolism. 2001;2:37–51.

    1. For a review of metal-catalyzed α-arylations of carbonyl compounds, including a discussion of the significance of the target compounds, see: Johansson CCC, Colacot TJ. Angew Chem, Int Ed. 2010;49:676–707.See also: Bellina F, Rossi R. Chem Rev. 2010;110:1082–1146.

    1. α-Arylcarbonyl compounds that bear tertiary α stereocenters are prone to racemization under the Brønsted-basic reaction conditions. (a) For a pioneering report on the catalytic asymmetric synthesis of α-arylcarbonyl compounds that bear quaternary α stereocenters, see: Åhman J, Wolfe JP, Troutman MV, Palucki M, Buchwald SL. J Am Chem Soc. 1998;120:1918–1919.For a review of catalytic enantioselective α-arylations of carbonyl compounds, see: Burtoloso ACB. Synlett. 2009:320–327.

    1. Negishi reactions of α-bromoketones: Lundin PM, Esquivias J, Fu GC. Angew Chem, Int Ed. 2009;48:154–156.

    1. Hiyama reactions of α-bromoesters: Dai X, Strotman NA, Fu GC. J Am Chem Soc. 2008;130:3302–3303.

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