The first enantioselective organocatalytic reductive amination reaction has been accomplished. The development of a new chiral phosphoric acid catalyst has provided a convenient strategy for the enantioselective construction of protected primary amines and provided a highly stereoselective method for the reductive amination of heterocyclic amines. A diverse spectrum of ketone and amine substrates can be accommodated in high yield and excellent enantioselectivity. This new protocol realizes a key benefit of reductive amination versus imine reduction, in that ketimines derived from alkyl−alkyl ketones are unstable to isolation, a fundamental limitation that is comprehensively bypassed using this direct organocatalytic reductive amination.

Enantioselective Organocatalytic Reductive Amination

Asymmetric synthesis of isoquinoline alkaloids

A Powerful Brønsted Acid Catalyst for the Organocatalytic Asymmetric Transfer Hydrogenation of Imines

Phase-transfer catalysis has been recognized as a powerful method for establishing practical protocols for organic synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large-scale synthesis, and the environmentally benign nature of the reaction system. Since the pioneering studies on highly enantioselective alkylations promoted by chiral phase-transfer catalysts, this research field has served as an attractive area for the pursuit of "green" sustainable chemistry. A wide variety of asymmetric transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable organic compounds in the past several decades, especially in recent years.

Recent Developments in Asymmetric Phase-Transfer Reactions

Catalytic enantioselective allylation of carbonyl compounds and imines.

Reactions of nitric oxide (NO) with amines in organic solvents were studied using Hantzsch dihydropyridines and aromatic primary amines as substrates. Hantzsch dihydropyridines are readily oxidized by nitric oxide to give the corresponding pyridines in quantitative yields. The addition of oxygen accelerates the reaction rate considerably. On the other hand, aromatic primary amines give deaminated products by the reaction with nitric oxide only in the presence of oxygen in ethereal solvents or chloroform.

Reaction of Nitric Oxide with Amines

Formal Total Synthesis of (−)-Emetine Using Catalytic Asymmetric Allylation of Cyclic Imines as a Key Step

A selective reductive amination of aldehydes by the use of Hantzsch dihydropyridines as reductant

A catalytic asymmetric allylation of 3,4-dihydroisoquinoline was carried out with allyltrimethoxylsilane-Cu as the nucleophile in the presence of DTBM-SEGPHOS as the chiral ligand to afford corresponding chiral 1-allyltetrahydroisoquinoline derivatives in good yield and stereoselectivity. The allyl adduct thus obtained was applied to the synthesis of several isoquinoline alkaloids such as crispine A and homolaudanosine. The reaction was further used for the synthesis of the isoquinoline moiety of schulzeine A.

Michiko Miyazaki

Papers

Reaction of Nitric Oxide with Amines

Formal Total Synthesis of (−)-Emetine Using Catalytic Asymmetric Allylation of Cyclic Imines as a Key Step

A selective reductive amination of aldehydes by the use of Hantzsch dihydropyridines as reductant

Catalytic asymmetric allylation of 3,4-dihydroisoquinolines and its application to the synthesis of isoquinoline alkaloids.

Reductive amination of aldehydes and ketones by a Hantzsch dihydropyridine using scandium triflate as a catalyst