Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

Abstract

Chiral amines are key structural motifs present in a wide variety of natural products, drugs, and other biologically active compounds. During the past decade, significant advances have been made with respect to the enantioselective synthesis of chiral amines, many of them based on catalytic asymmetric hydrogenation (AH). The present review covers the use of AH in the synthesis of chiral amines bearing a stereogenic center either in the α, β, or γ position with respect to the nitrogen atom, reported from 2010 to 2020. Therefore, we provide an overview of the recent advances in the AH of imines, enamides, enamines, allyl amines, and N-heteroaromatic compounds.

Iridium-catalyzed direct asymmetric reductive amination utilizing primary alkyl amines as the N-sources

“…1a ). The increasing demand has driven the development of novel and efficient methods for their synthesis 1 – 3 , including two practical and highly efficient routes, asymmetric hydrogenation 4 – 9 and reductive amination 10 – 15 (Fig. 1b ).…”

Enzymatic approaches to site-selective oxidation of quinoline and derivatives

“…4,5 As a consequence, methods for their synthesis have attracted a significant amount of attention. 2,6–11…”

“…1) are one type of the main building blocks of living systems, being the principle components of naturally occurring alkaloids, such as (−)-quinine (5), galipine (6) and camptothecin (7) for 1 (Fig. 2a), 1 (−)-angustureine (8), (−)-cuspareine (9), (−)-galipeine (10) and (−)-galipinine (11) for 2 (Fig. 2b), 1b,2 berberine (12), palmatine (13), jatrorrhizine (14) and sanguinarine (15) for 3 (Fig.…”

“…4,5 As a consequence, methods for their synthesis have attracted a significant amount of attention. 2, [6][7][8][9][10][11] In the past, most of the focus of synthesis of compounds with these nitrogenous heterocyclic rings as core frameworks has been on the use of chemical methods. For example, procedures of Conrad-Limpachs, 12 Pfitzinger, 13 Friedländer, 14 Skraup 15,16 and Doebner-Miller 17,18 reactions have been developed for synthesis of quinoline-containing compounds, whereas reduction of nitrogenous heterocyclic ring of the respective quinoline derivative, formation of single or multiple carbon-carbon bonds, and nitrogenous heterocyclic ring contraction and expansion have been common strategies for synthesis of tetrahydroquinoline-containing compounds.…”

Highly Enantioselective Synthesis of N‐Unprotected Unnatural α‐Amino Acid Derivatives by Ruthenium‐Catalyzed Direct Asymmetric Reductive Amination

“…However, it requires the manipulation of toxic cyanide reagents and suffers from the harsh conditions for the hydrolysis of the α‐amino nitriles (Scheme 1a) [5] . Effective alternative approaches have also been developed, such as asymmetric hydrogenation of dehydroamino acids and α‐iminoesters, [6, 7] enantioselective nucleophilic addition to α‐iminoesters, [8] alkylation of glycine derivatives via chiral phase‐transfer catalysis (PTC), [9] and enantioselective carbene insertion into N−H bonds of amines or amides (Scheme 1b–e) [10, 11] . However, a fact that cannot be ignored in the aforementioned methods is that they usually yield N‐protected α‐amino acids, thereby requiring additional deprotection steps to release the synthetically more versatile N‐unprotected α‐amino acids.…”