Metal hydrides imines

The other way of reducing nitriles to aldehydes involves using a metal hydride reducing agent to add 1 mol of hydrogen and hydrolysis, in situ, of the resulting imine (which is undoubtedly coordinated to the metal). This has been carried out with LiAlH4, LiAlH(OEt)3, LiAlH(NR2)3, and DIBAL-H. The metal hydride method is useful for aliphatic and aromatic nitriles. 

Hydrogen will not reduce ketones or imines using CATHy or related catalysts. Inorganic hydrogen donors that have been used include dithionite and di-hydrogenphosphite salts, metal hydrides such as sodium borohydride, and sodium cyanoborohydride. Recently, amines have been shown to function as hydrogen donors with some catalysts. The enzymic cofactor NADH can be used stoichiometrically, and the potential exists to use this catalytically [56]. 

C. Reduction of Imines with Chiral Metal Hydride Reagents. 112... 

Imine formation is an important reaction. It generates a C-N bond, and it is probably the most common way of forming heterocyclic rings containing nitrogen (see Section 11.10). Thns, cycliza-tion of 5-aminopentanal to A -piperideine is merely intramolecular imine formation. A further property of imines that is shared with carbonyl groups is their susceptibility to reduction via complex metal hydrides (see Section 7.5). This allows imines to be... 

The combined reaction thus involves initial formation of the iminium ion from the carbonyl compound and amine at pH 6, and this intermediate is then reduced by the complex metal hydride to give the amine. This can also he a way of making methyl-suhstituted amines via intermediate imines with formaldehyde. 

The reduction of imines can be performed with zinc powder in 5% aq. NaOH solution without any organic solvents under mild conditions (Tsukinoki et al., 1998). In comparison with other conventional methods, some advantages of this method are the fact that, since the reaction can be done in water at room temperature under atmospheric pressure, it is safe, and that hydrogen gas is not necessary because the proton source is water. Furthermore, Zn powder is cheap compared with metal hydrides, hydrogenation catalyst, and lanthanides, and is not sensitive to oxygen and water. 

Asymmetric hydrometallation of ketones and imines with H-M (M = Si, B, Al) catalyzed by chiral transition-metal complexes followed by hydrolysis provides an effective route to optically active alcohols and amines, respectively. Asymmetric addition of metal hydrides to olefins provides an alternative and attractive route to optically active alcohols or halides via subsequent oxidation of the resulting metal-carbon bonds (Scheme 2.1). 

Most often, asymmetry is created on conversion of a prochiral trigonal carbon of carbonyl, enol, imine, enamine, and olefin groups to a tetrahedral center. One of the easiest methods for the preparation of optically active alcohols is the reduction of prochiral ketones. This transformation is achieved using chiral reductants in which chiral organic moieties are ligated to boron or to a metal hydride (Table 4.9). 

A photochemical ring construction similar to that described in Scheme 5 was used in the synthesis of the aromatic lycorine alkaloid ungeremine (51) (Scheme 6). Photocyclization of the somewhat inaccessible imine (48) gave the phenanthridine derivative (49) in 21 % yield which upon metal hydride reduction and cyclization with phosphorus tribromide afforded the quaternary salt (50) which was shown to be identical with the methyl ether of ungeremine (51) obtained as shown. 

Reduction using complex metal hydrides. A (salen)Co complex promotes asymmetric reduction of conjugated carboxamides. Similarly, A-diphenylphosphinyl imines are converted to the substituted amines in chiral forms. 

A popular and effective method for converting aldehydes to amines is through a reductive amination protocol. Typically, the aldehyde and amine react to fonn an intermediate imine or iminiiim ion and tlien a reducing agent (i.e., sodium triacetoxyborohydride) is added to carry out the reduction of the intermediate species to afford the amine. The reaction is accelerated in the presence of acetic acid (0.1 -3 equivalents). Reviews (a) Baxter, E. W. Reitz, A. B. Org. React. 2002, 59, 1-714. (b) Hutchins, R. O. In Comprehensive Organic Synthesis Trost, B. M. Fleming, L, Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 1.2 Reduction of C=N to CHNH by Metal Hydrides, pp. 25-54. 

Basic system both imines and amines are basic compounds this can lead to deprotonation of the metal hydrides formed as intermediates in the catalytic cycle and finally cause a decomposition of the active catalyst. 

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