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. 2018 Feb 19;57(8):2233-2237.
doi: 10.1002/anie.201710915. Epub 2018 Jan 18.

Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives

Bin Hu  1 , Li Deng  1
Affiliations

Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives

Bin Hu et al. Angew Chem Int Ed Engl. .

Abstract

Novel cinchona alkaloid derived chiral phase-transfer catalysts enabled the highly chemo-, regio-, diastereo-, and enantioselective umpolung addition of trifluoromethyl imines to α,β-unsaturated N-acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0 mol %, this new catalytic asymmetric transformation provides facile and high-yielding access to highly enantiomerically enriched chiral trifluoromethylated γ-amino acids and γ-lactams.

Keywords: C−C bond formation; amino acids; asymmetric catalysis; phase-transfer catalysis; umpolung.

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Figures

Figure 1.
Figure 1.
Biologically active and medicinally important trifluoromethylated γ-amino acids.
Figure 2.
Figure 2.
Single crystal X-ray structure of ion-pair complex I. The phenyl ring of 4-nitrophenoxide is highlighted. The protons and solvent molecules have been hided for clarity (C: grey, O: red, N: blue, Cl: green).
Scheme 1.
Scheme 1.
Catalytic asymmetric approaches to γ-substituted γ-amino acid derivatives
Scheme 2.
Scheme 2.
Gram-scale reactions and synthetic applications
See this image and copyright information in PMC

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