The carbon-nitrogen double bonds in imines are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles towards carbon nucleophiles in reactions that form carbon-carbon bonds, thereby serving as one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings. If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via carbon-carbon bond-forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric umpolung reactions of imines (in which the imines act as nucleophiles) remains uncharted territory, in spite of the far-reaching impact such reactions would have in organic synthesis. Here we report the discovery and development of new chiral phase-transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines with the carbon electrophile enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed to react with enals in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mole per cent catalyst with a moisture- and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach to chiral amino compounds.

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Catalytic asymmetric umpolung reactions of imines.

An enantioselective protonation strategy has been successfully applied to the synthesis of chiral α-tertiary azaarenes. With a dual catalytic system involving a chiral phosphoric acid and a dicyanopyrazine-derived chromophore (DPZ) photosensitizer that is mediated by visible light, a variety of α-branched 2-vinylpyridines and 2-vinylquinolines with N-aryl glycines underwent a redox-neutral, radical conjugate addition–protonation process and provided valuable chiral 3-(2-pyridine/quinoline)-3-substituted amines in high yields with good to excellent enantioselectivities (up to >99% ee). An application of this methodology to a two-step synthesis of the enantiomerically pure medicinal compound pheniramine (Avil) is also presented.

Conjugate Addition-Enantioselective Protonation of N-Aryl Glycines to α-Branched 2-Vinylazaarenes via Cooperative Photoredox and Asymmetric Catalysis.

This review covers the use of 2-azaallyl anions, 2-azaallyl cations, and 2-azaallyl radicals in organic synthesis up through June 2018. Particular attention is paid to both foundational studies and recent advances over the past decade involving semistabilized and nonstabilized 2-azaallyl anions as key intermediates in various carbon–carbon and carbon–heteroatom bond-forming processes. Both transition-metal-catalyzed and transition-metal-free transformations are covered. Azomethine ylides, which have received significant attention elsewhere, are discussed briefly with the primary focus on critical comparisons with 2-azaallyl anions in regard to generation and use.

2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides

For the planning of an organic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, back to ready available starting materials, is well established In contrast, such concepts just get developed for biocatalytic routes In this Review we highlight functional group interconversions catalyzed by enzymes The article is organized rather by chemical bonds formed-exemplified for C-N, C-O- and C-C-bonds-and not by enzyme classes, covering a broad range of reactions to incorporate the desired functionality in the target molecule Furthermore, the successful use of biocatalysts, also in combination with chemical steps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptin and Atorvastatin This Review also provides some basic guidelines to choose the most appropriate enzyme for a targeted reaction keeping in mind aspects like commercial availability, cofactor-requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymes for synthetic applications

https://onlinelibrary.wiley.com/doi/pdf/10.1002/chem.201702235

A Retrosynthesis Approach for Biocatalysis in Organic Synthesis.

Organocatalytic asymmetric multicomponent cascade reaction via 1,3-proton shift and [3+2] cycloaddition: an efficient strategy for the synthesis of oxindole derivatives

This paper describes an effective chiral base-catalyzed biomimetic transamination of α-keto esters using simple benzyl amines. A wide variety of α-amino esters containing various functional groups can be synthesized in high enantioselectivity and reasonable yield.

Organocatalytic asymmetric biomimetic transamination: from α-keto esters to optically active α-amino acid derivatives.

An efficient synthesis of optically active trifluoromethyl aldimines via asymmetric biomimetic transamination

Transamination of α-keto acids with transaminases and pyridoxamine phosphate is an important process to form optically active α-amino acids in biological systems. Various biomimetic transamination systems have been developed for carbonyl compounds including α-keto acid derivatives, fluoroalkyl ketones, and unactivated ketones with chiral vitamin B6 analogues, artificial transaminase mimics, chiral nitrogen sources, and chiral catalysts. This review provides a brief summary of this area.

Progress in asymmetric biomimetic transamination of carbonyl compounds

An Efficient Asymmetric Biomimetic Transamination of α-Keto Esters to Chiral α-Amino Esters

An asymmetric biomimetic transamination of aromatic ketones to optically active amines with o-HOPhCH2NH2 as amine source catalyzed by hydroquinine-derived chiral base is described. Up to 85% ee was obtained.

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Ying Xie

Papers

Organocatalytic asymmetric biomimetic transamination: from α-keto esters to optically active α-amino acid derivatives.

An efficient synthesis of optically active trifluoromethyl aldimines via asymmetric biomimetic transamination

Progress in asymmetric biomimetic transamination of carbonyl compounds

An Efficient Asymmetric Biomimetic Transamination of α-Keto Esters to Chiral α-Amino Esters

Organocatalytic asymmetric biomimetic transamination of aromatic ketone to optically active amine