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. 2015 Feb 11;137(5):2042-6.
doi: 10.1021/ja512529e. Epub 2015 Jan 27.

Palladium(II)-catalyzed highly enantioselective C-H arylation of cyclopropylmethylamines

Kelvin S L Chan  1 , Hai-Yan Fu, Jin-Quan Yu
Affiliations

Palladium(II)-catalyzed highly enantioselective C-H arylation of cyclopropylmethylamines

Kelvin S L Chan et al. J Am Chem Soc. .

Abstract

C-H arylation via a Pd(II)/Pd(IV) catalytic cycle has been one of the most extensively studied C-H activation reactions since the 1990s. Despite the rapid development of this reaction in the past two decades, an enantioselective version has not been reported to date. Herein, we report a Pd(II)-catalyzed highly enantioselective (up to 99.5% ee) arylation of cyclopropyl C-H bonds with aryl iodides using mono-N-protected amino acid (MPAA) ligands, providing a new route for the preparation of chiral cis-aryl-cyclopropylmethylamines. The enantiocontrol is also shown to override the diastereoselectivity of chiral substrates.

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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Drugs containing cyclopropylmethylamine moieties
Scheme 1
Scheme 1
Scale up and deprotection of triflamide.
See this image and copyright information in PMC

References

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    1. For an intermolecular example of enantioselective Pd(0)-catalyzed C(sp3)–H activation, see: Renaudat A, Jean-Gérard L, Jazzar R, Kefalidis CE, Clot E, Baudoin O. Angew Chem, Int Ed. 2010;49:7261.

    1. For an example of Pd-catalyzed atropselective arylation, see: Yamaguchi K, Yamaguchi J, Studer A, Itami K. Chem Sci. 2012;3:2165.

    1. For intermolecular examples of enantioselective Pd(II)/MPAA-catalyzed C(sp2)–H activation and subsequent coupling with organoboron reagents, see: Shi BF, Maugel N, Zhang YH, Yu JQ. Angew Chem, Int Ed. 2008;47:4882.Gao DW, Shi YC, Gu Q, Zhao ZL, You SL. J Am Chem Soc. 2013;135:86.

    1. For intermolecular examples of enantioselective Pd(II)/MPAA-catalyzed C(sp2)–H activation and subsequent olefination, see: Shi BF, Zhang YH, Lam JK, Wang DH, Yu JQ. J Am Chem Soc. 2009;132:460.Pi C, Li Y, Cui X, Zhang H, Han Y, Wu Y. Chem Sci. 2013;4:2675.

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