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. 2020 Nov 27;12(4):1445-1450.
doi: 10.1039/d0sc05269h.

Construction of chiral α- tert-amine scaffolds via amine-catalyzed asymmetric Mannich reactions of alkyl-substituted ketimines

Chihiro Homma  1 , Aika Takeshima  1 , Taichi Kano  1 , Keiji Maruoka  2   3
Affiliations

Construction of chiral α- tert-amine scaffolds via amine-catalyzed asymmetric Mannich reactions of alkyl-substituted ketimines

Chihiro Homma et al. Chem Sci. .

Abstract

Stereoselective Mannich reactions of aldehydes with ketimines provide chiral β-amino aldehydes that bear an α-tert-amine moiety. However, the structural variation of the ketimines is limited due to the formation of inseparable E/Z isomers, low reactivity, and other synthetic difficulties. In this study, a highly diastereodivergent synthesis of hitherto difficult-to-access β-amino aldehydes that bear a chiral α-tert-amine moiety was achieved using the amine-catalyzed Mannich reactions of aldehydes with less-activated Z-ketimines that bear both alkyl and alkynyl groups.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Alkynyl-substituted ketimines for asymmetric reactions.
Scheme 2
Scheme 2. Amine-catalyzed asymmetric Mannich reaction of Z-ketimines.
Scheme 3
Scheme 3. Synthesis of N-Boc-protected Z-ketimines.
Fig. 1
Fig. 1. X-ray crystal structure of syn-2k.
Fig. 2
Fig. 2. Transition state models for asymmetric Mannich reactions catalyzed by l-proline (TS2) or (S,R)-7 (TS3).
Scheme 4
Scheme 4. Transformations of the Mannich product anti-2a.
See this image and copyright information in PMC

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