Complex borohydrides reductive amination

Ketimines are reduced to amines very easily by catalytic hydrogenation, by complex hydrides and by formic acid. They are intermediates in reductive amination of ketones (p. 134). An example of the reduction of a ketimine is conversion of 3-aminocarbonyl-2,3-diphenylazirine to the corresponding aziridine by sodium borohydride (yield 73%), by potassium borohydride (yield 71%) and by sodium bis (2-methoxyethoxy) aluminum hydride (yield 71%) [939]. 

Treatment of aldehydes or ketones with ammonia, primary or secondary amines in reducing media is called reductive alkylation (of ammonia or amines) or reductive amination (of aldehydes or ketones). Reducing agents are most frequently hydrogen in the presence of catalysts such as platinum, nickel or Raney nickel [955], complex borohydrides [705, 954, 955], formaldehyde or formic acid [522]. 

Mechanistic details involved in imine and carbonyP - reductions are undoubtedly similar, although thorough investigations of the former are lacking. Certainly, hydride transfer to the electrophilic carbon, with or without prior activation by protonation or complexation is essential for both types of ir-systems (Scheme 1). Whether or not alcohol solvents participate in imine reductions by borohydride (in the absence of added acid) to furnish the amine proton (as is the case with carbonyls) is not known and must await detailed kinetic study and analysis of the initial intermediates formed before hydrolysis. Direct, in situ, reductive amination with NaBHsCN has been attributed to initial, reversible formation (via an intermediate hydroxyamine, (1) of an iminium ion (2) from carbonyls and amines followed by rapid attack by hydride (Scheme 2). However, the inermess of an imine (partial structure 3) to the usual reductive... 

Cyclopropenylium ions 1 were converted into the corresponding cyclopropenes 2 by the addition of hydride ion derived from various hydride sources, such as lithium aluminum hydride,sodium borohydride, borane-amine complex, triethylsilane, and tributyl-tin hydride. Particularly in the case of borohydride reduction of the diphenylcyclo-propenylium ion, the order of reagent addition was quite important. The slow addition of an acetonitrile solution of the cyclopropenylium salt into a solution of the borohydride gave the cyclopropene derivative,whereas the inverse order of addition resulted in quantitative formation of 1,2,4,5-tetraphenylbenzene (see Section 2.1.2.3.), No such precaution of the inverse addition was required in the case of borane-amine reduction of the l-chloro-2,3-diphenyl-cyclopropenylium ion. ... 

The heptanuclear iron carbonyl cluster [Fe3(CO)u(/u-H)]2-Fe(DMF)4 (178) acted as an efficient catalyst in the reduction of carboxamides by l,2-bis(dimethylsilyl)benzene in toluene to the corresponding amines in high yields. Several tertiary and secondary amides including a sterically crowded amide were also reduced smoothly A review of the development of optically active cobalt complex catalysts for enan-tioselective synthetic reactions has addressed the applications of ketoiminatocobalt(II) complexes such as (5)-MPAC (179) and (5)-AMAC (180), transition-state models for borohydride reduction, halogen-free reduction by cobalt-carbene complexes. 

Optically active (+)-methyl-2-thienylmethanol has been obtained through reduction of 2-acetylthiophen with a lithium aluminium hydride-quinine complex. The 2-thienyl analogues of ephedrine and 0-ephedrine have been synthesized from 2-propionylthiophen via the a-bromo-derivative and the methylamino-ketone, followed by borohydride reduction. The amines were resolved into optical antipodes. Through the Claisen condensation between 2-acetylthiophen and ethyl formate, followed by the reaction with secondary amines, compounds of type (164) were obtained. 

Imines can be reduced to amines by catalytic hydrogenation, or by reduction with lithium aluminium hydride, sodium borohydride or amine-borane complexes . For many purposes, it is not necessary to prepare the imine as the desired amine can, at least in principle, be obtained by catalytic reduction of a mixture of the corresponding carbonyl compound and precursoral amine (reaction 95) The... 

High yields of amines have also been obtained by reduction of amides with an excess of magnesium aluminum hydride (yield 100%) [577], with lithium trimethoxyaluminohydride at 25° (yield 83%) [94] with sodium bis(2-methoxy-ethoxy)aluminum hydride at 80° (yield 84.5%) [544], with alane in tetra-hydrofuran at 0-25° (isolated yields 46-93%) [994, 1117], with sodium boro-hydride and triethoxyoxonium fluoroborates at room temperature (yields 81-94%) [1121], with sodium borohydride in the presence of acetic or trifluoroacetic acid on refluxing (yields 20-92.5%) [1118], with borane in tetrahydrofuran on refluxing (isolated yields 79-84%) [1119], with borane-dimethyl sulflde complex (5 mol) in tetrahydrofuran on refluxing (isolated yields 37-89%) [1064], and by electrolysis in dilute sulfuric acid at 5° using a lead cathode (yields 63-76%) [1120]. 

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