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. 2022 Mar 7;13(13):3796-3802.
doi: 10.1039/d2sc00386d. eCollection 2022 Mar 30.

Enantioselective synthesis of α-amino ketones through palladium-catalyzed asymmetric arylation of α-keto imines

Wei Wen  1 , Zhao-Pin Ai  1 , Chang-Lin Yang  1 , Chao-Xing Li  1 , Zhu-Lian Wu  1 , Tian Cai  1 , Qi-Xiang Guo  1
Affiliations

Enantioselective synthesis of α-amino ketones through palladium-catalyzed asymmetric arylation of α-keto imines

Wei Wen et al. Chem Sci. .

Abstract

Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Catalytic asymmetric reactions of C-carbonyl imines/iminium ions.
Scheme 2
Scheme 2. Effect of nitrogen protecting groups.
Scheme 3
Scheme 3. The reaction of 1a with arylboronic acids bearing biologically active moieties.
Scheme 4
Scheme 4. Gram-scale synthesis of (1R, 2S)-2-amino-1,2-diphenylethanol 9.
Fig. 1
Fig. 1. (a) 1H-NMR spectrum of 1a (0.02 mmol) and Pd(TFA)2 (0.02 mmol) in CDCl3 (0.5 mL) after stirring for 12 hours at 40 °C. (b) 1H-NMR spectrum of 1a (0.02 mmol) in CDCl3 (0.5 mL) after stirring for 12 hours at 40 °C. (c) 1H-NMR spectrum of phenylglyoxal.
Fig. 2
Fig. 2. (a) HRMS spectrum of 1a (0.1 mmol) in CF3CH2OH (0.5 mL) after stirring for 4 hours at 40 °C. (b) HRMS spectrum of 1a (0.1 mmol), Pd(TFA)2 (10 mol%) and L10 (12 mol%) in CF3CH2OH (0.5 mL) after stirring for 4 hours at 40 °C.
Fig. 3
Fig. 3. (a) Recovered yields and ee values of 1a at different reaction times. (b) Yields and ee values of 3a at different reaction times.
Scheme 5
Scheme 5. Proposed catalytic cycle.
See this image and copyright information in PMC

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