Imine catalytic asymmetric reduction

Catalytic asymmetric reduction of unsaturated compounds is one of the most reliable methods used to synthsize the corresponding chiral saturated products. Chiral transition metal complexes repeatedly activate an organic or inorganic hydride source, and transfer the hydride to olefins, ketones, or imines from one... 

Hermitage S, Howard JAK, Jay D, Pritchard RG, Probert MR, Whiting A (2004) Mechanistic studies on the formal aza-Diels-Alder reactions of N-aryl imines evidence for the non-concertedness under Lewis-acid catalysed conditions. Org Biomol Chem 2 2451-2460 Hoffmann S, Nicoletti M, List B (2006) Catalytic asymmetric reductive ami-nation of aldehydes via dynamic kinetic resolution. J Am Chem Soc 128 13074-13075... 

This chapter also includes a discussion of the catalytic asymmetric reduction of the C=N bond of imines. This transformation has been achieved with high ee using both metal-based catalysts and also organic Br0nsted acids. 

Lee, Yun-Choi, et al. described the synthesis of optically active tetrahydroisoquinoline alkaloids, (R)-(+)-higen-amine, (5)-(—)-higenamine, and their optically active 1-naphthylmethyl analogs, via enantioselective hydrogenation of the dihydroisoquinoline intermediates 212 as a key step. Catalytic asymmetric reduction of imine was accomplished with Noyori s catalyst RuCl[(5, 5)-TsDPEN... 

The first catalytic asymmetric reduction of imines, as summarized in Equation 14, was achieved by Kagan in 1973 [135]. Since then a number of catalytic enantioselective imine reductions involving hydrogenations or hydrosilylations have been developed [20, 33, 36, 37]. 

Catalytic Asymmetric Reductions of Imines and /mine Derivatives... 

The paramount significance of chiral amines in pharmaceutical and agrochemical substances drives the development of efficient catalytic asymmetric methods for their formation. In contrast to the high enantioselectivities observed in asymmetric reduction of both alkenes and ketones, only limited success has been achieved in the enantiose-lective hydrogenation of imines [118]. Currently, there are few efficient chiral catalytic systems available for the asymmetric hydrogenation of imines. 

Catalytic asymmetric synthesis of enantiopure diaryl-methanols and -methylamines (important pharmaceutical intermediates) has been reviewed (76 references), focusing on (i) aryl transfers on to aryl-aldehydes and -imines and (ii) asymmetric reductions of diaryl-ketones and -ketoimines.284... 

A catalytic asymmetric in situ reduction of N-H imines has been achieved in a sequence in which trifluoroacetophenones, ArCOCF3, are first converted to silylimines [using LiN(SiMe3)2], and then on to give trifluoromethylated amine salts, Ar-C(CF3)-NH2.HC1, in good to excellent yield and ee.5s The intermediate N-H imines can be isolated via methanolysis of the N-Si bond, while the enantioselective reduction can be carried out using a chiral borane auxiliary. 

The catalytic, asymmetric hydrogenations of alkenes, ketones and imines are important transformations for the synthesis of chiral substrates. Organic dihydropyridine cofactors such as dihydronicotinamide adenine dinucleotide (NADH) are responsible for the enzyme-mediated asymmetric reductions of imines in living systems [86]. A biomimetic alternative to NADH is the Hantzsch dihydropyridine, 97. This simple compound has been an effective hydrogen source for the reductions of ketones and alkenes. A suitable catalyst is required to activate the substrate to hydride addition [87-89]. Recently, two groups have reported, independently, the use of 97 in the presence of a chiral phosphoric acid (68 or 98) catalyst for the asymmetric transfer hydrogenation of imines. 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

Kadyrov R, Riermeier TH (2003) Highly enantioselective hydrogen-transfer reductive amination catalytic asymmetric synthesis of primary amines. Angew Chem Int Ed Engl 42 5472-5474 Kang Q, Zhao ZA, You SL (2007) Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. J Am Chem Soc 129 1484-1485... 

For a general overview of the reduction of imines, see the following (a) Morrison, J.D. (1983) Asymmetric Synthesis, vol. 2, Academic, New York (b) Noyori, R. (1994) Asymmetric Catalysis in Organie Synthesis, John WUey Sons, New York (c) Ojima, I. (2000) Catalytic Asymmetric Synthesis, 2nd edn, John WUey Sons, New York ... 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

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