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. 2012 Apr 4;134(13):5794-7.
doi: 10.1021/ja301612y. Epub 2012 Mar 26.

New directing groups for metal-catalyzed asymmetric carbon-carbon bond-forming processes: stereoconvergent alkyl-alkyl Suzuki cross-couplings of unactivated electrophiles

Ashraf Wilsily  1 , Francesco Tramutola, Nathan A Owston, Gregory C Fu
Affiliations

New directing groups for metal-catalyzed asymmetric carbon-carbon bond-forming processes: stereoconvergent alkyl-alkyl Suzuki cross-couplings of unactivated electrophiles

Ashraf Wilsily et al. J Am Chem Soc. .

Abstract

The ability of two common protected forms of amines (carbamates and sulfonamides) to serve as directing groups in Ni-catalyzed Suzuki reactions has been exploited in the development of catalytic asymmetric methods for cross-coupling unactivated alkyl electrophiles. Racemic secondary bromides and chlorides undergo C-C bond formation in a stereoconvergent process in good ee at room temperature in the presence of a commercially available Ni complex and chiral ligand. Structure-enantioselectivity studies designed to elucidate the site of binding to Ni (the oxygen of the carbamate and of the sulfonamide) led to the discovery that sulfones also serve as useful directing groups for asymmetric Suzuki cross-couplings of racemic alkyl halides. To our knowledge, this investigation provides the first examples of the use of sulfonamides or sulfones as effective directing groups in metal-catalyzed asymmetric C-C bond-forming reactions. A mechanistic study established that transmetalation occurs with retention of stereochemistry and that the resulting Ni-C bond does not undergo homolysis in subsequent stages of the catalytic cycle.

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Figures

Figure 1
Figure 1
Outline of a mechanism for nickel-catalyzed enantioselective Suzuki cross-couplings of unactivated secondary alkyl halides.
See this image and copyright information in PMC

References

    1. For reviews and leading references on directed reactions, see: Hoveyda AH, Evans DA, Fu GC. Chem. Rev. 1993;93:1307–1370. Rousseau G, Breit B. Angew. Chem. Int. Ed. 2011;50:2450–2494.

    1. (a) Aromatic ring: Saito B, Fu GC. J. Am. Chem. Soc. 2008;130:6694–6695. (b) Oxygen of a carbonyl group: Owston NA, Fu GC. J. Am. Chem. Soc. 2010;132:11908–11909. (c) Nitrogen of an arylamine: Lu Z, Wilsily A, Fu GC. J. Am. Chem. Soc. 2011;133:8154–8157. (d) Amide: Zultanski SL, Fu GC. J. Am. Chem. Soc. 2011;133:15362–15364.

    1. For reviews and leading references on cross-couplings of alkyl electrophiles, including enantioselective processes, see: Rudolph A, Lautens M. Angew. Chem. Int. Ed. 2009;48:2656–2670. Glorius F. Angew. Chem. Int. Ed. 2008;47:8347–8349. (c) Reference .

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