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. 2006 Mar 8;128(9):2778-9.
doi: 10.1021/ja057498v.

A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones

Barry M Trost  1 , Jaray Jaratjaroonphong, Vichai Reutrakul
Affiliations

A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones

Barry M Trost et al. J Am Chem Soc. .

Abstract

The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.

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Figures

Scheme 1
Scheme 1
Anti- and Syn-β-Amino Alcohol Synthesis
Scheme 2
Scheme 2
Generation of Dinuclear Zinc Catalyst
See this image and copyright information in PMC

References

    1. Reviews:Denmark SE, Nicaise OJ-C. In: Comprehensive Asymmetric Catalysis. Jacobsen EN, Pfaltz A, Yamamoto H, editors. Springer; Heidelberg: 1999. pp. 923–961.Kleinmann EF. In: Comprehensive Organic Synthesis. Trost BM, editor. Vol. 2. Pergamon Press; New York: 1991. Chapter 4.1.Arend M, Westermann B, Risch N. Angew. Chem. Int. Ed. 1998;37:1044.Kobayashi S, Ishitani H. Chem. Rev. 1999;99:1069.

    1. A review of the direct Mannich reaction:Córdova A. Acc. Chem. Res. 2004;37:102.

    1. Selected examples for metal catalysts, see:Juhl K, Gathergood N, Jørgensen KA. Angew. Chem. Int. Ed. 2001;40:2995.Trost BM, Terrell LR. J. Am. Chem. Soc. 2003;125:338.Matsunaga S, Kumagai N, Harada S, Shibasaki M. J. Am. Chem. Soc. 2003;125:4712.Matsunaga S, Yoshida T, Morimoto H, Kumagai N, Shibasaki M. J. Am. Chem. Soc. 2004;126:8777.Harada S, Handa S, Matsunaga S, Shibasaki M. Angew. Chem. Int. Ed. 2005;44:4365.For organocatalysts, see:List B. J. Am. Chem. Soc. 2000;122:9336.List B, Pojarliev P, Biller WT, Martin HJ. J. Am. Chem. Soc. 2002;124:827.Córdova A, Notz W, Zhong G, Betancort JM, Barbas CF., III J. Am. Chem. Soc. 2002;124:1842.

    1. Dpp-imine was prepared by treatment of N-(diphenylphosphinoyl)-α-(p-toluenesulfonyl) alkylamine 9 with sat. aq. NaHCO3 in CH2Cl2: see Supporting Information for details. For preparation of 9, see:Côté A, Boezio AA, Charette AB. Proc. Natl. Acad. Sci. U.S.A. 2004;101:5405.

    1. Boc-imine was prepared by treatment of N-(N-tert-butyloxy-carbonyl)-α-(phenylsulfonyl) alkylamine 10 with 1.5 M aq. K2CO3 in CH2Cl2: see Supporting Information for details. For preparation of 10, see:Pearson WH, Lindbeck AC, Kampf JW. J. Am. Chem. Soc. 1993;115:2622.

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