Reduction, of imines

Catalytic asymmetric hydrogenation of prochiral Schiff bases has been reviewed.57 (g) 

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. 

1-Substituted-l-(pyridine-2-yl)methylamines (13, X = CHNH2) have been prepared diastereoselectively by the reduction of enantiopure iV-p-toluenesulfinyl (g) ketimines [X = C=N- S(=0)-p-tolyl].61 

An achiral iridium catalyst gives high yields in hydrogenation of imines derived from acetophenone, and also imines of aliphatic ketones. An enantioselective version has been developed, using a chiral phosphoric acid as Brpnsted acid. This gives ees up to 98%, but at the expense of the reaction rate, slowed by the bulk of the BINOL-type phosphoric acid. 

Enantioselective hydrogenation of imines has been achieved via a cooperative catalysis involving an iridium(I) organometallic and an organocatalyst, with low-temperature nOe- and DoSy-NMR techniques being used to characterize a key ternary complex. (S) 

A cyclometallated iridium(ni) catalyst (44) bearing an imine ligand catalyses hydrogenation of imines, typically in an hour at 0.05 mol% loading/20 atm Hj/TS °C. It is selective for imines, is air-stable, and is probably turnover-limited by the hydride formation step. 

A new Ru- 7 -arene complex (45) acts as a C-based Lewis acid catalyst for the hydrogenation of aldimines at ambient temperature via a frustrated Lewis pair mechanism with 102 atm H2 in DCM at 25 °C, 1 mol% catalyst gives up to 99% amine in 8 h. The catalyst and its mechanism have been extensively characterized by X-ray crystallography and NMR, including deuteration experiments with D2 which prove that exchange is occurring ortho- and para- to the boron. 

In another frustrated Lewis pair route, a highly enantioselective metal-free hydrogenation of imines uses a BlNAP-derived diene as a ligand hydroboration of the alkenes in situ with HB(CgF5)2 generates a chiral bis-borane catalyst.  

The metal ion does, however, introduce a new subtlety into these reductions. The reduction of the two imine groups in the nickel(n) complex 4.10 is readily achieved with Na[BH4], The free tetraamine ligand would be expected to exhibit a facile pyramidal inversion at each nitrogen atom, whereas in the nickel(n) complex this inversion is not possible without significant weakening (or breaking) of the Ni-N bonds. In macrocyclic complexes it is very often found that the complex obtained by the reduction of a co-ordinated imine does not possess the same stereochemistry as that obtained by the direct reaction of the free amine with metal ion. 

The microwave synthesis of optically pure imines for subsequent diastereoselective boronate reduction at room temperature has been described50. The reduction of (1-azabuta-l,3-diene)tricarbonyliron(0) complexes and their free ligands using sodium 

A modified protocol of the Eschweiler-Clarke reaction, a reductive transamination, was also used for an efficient N-alkylation of hexahydroazepine and benzylamine in the presence of formic acid and aldehydes or ketones53. 

The Leuckart reductive animation of carbonyl compounds with ammonium formate or formamide was found to benefit strongly, when the reaction was carried out under solvent free conditions with microwave irradiation. Yields of N-alkylated formamides of up to 97% were produced in reaction times of about 30 min, as compared to thermal 

Ruthenium and iridium are commonly used in catalysts for this reaction. A selectively deuterated hydroxycyclopentadienyl ruthenium hydride catalyst has been employed to probe the mechanism 48 The relative rates of different steps determine whether the process is stereospecific (typically trans) or stereorandom. 

A water-soluble, recyclable ruthenium(II) complex including a chiral diamine ligand has been used for asymmetric transfer hydrogenation of cyclic imines and iminiums in water, with yields and ee up to 99%.49 

Homogeneous catalytic hydrogenation of imines has been carried out using cationic iridium hydride catalysts.50 The mechanistic possibilities are compared and contrasted with C=0 hydrogenations. 

A new class of chiral phosphine-oxazolines act as ligands in iridium-catalysed asymmetric hydrogenation of imines, and of alkenes, giving ees up to 99%.51 

Acyclic aromatic A-arylimines, Ar1-C(Me)=N-Ar2, have been reduced to the corresponding amine with up to 99% ee, using 1 atm of hydrogen and an iridium(I) catalyst bearing a chiral diphosphinoethane chelating ligand.52 

Aromatic ketimines are reduced enantioselectively to amines (50 atm H2/toluene/65°C/24h), using a cooperative catalysis involving Knolker s iron complex and a BINOL-derived hydrogen phosphate auxiliary, with P-NMR evidence supporting the bifunctional catalysis. A phosphine-free chiral cationic ruthenium complex catalyses enantioselective hydrogenation of IV-alkyl ketimines, including many heretofore problematic substrates. 0 

Evidence for low-valent and trimeric titanium alkoxide species in the reaction of phenylsilane and titanium(IV) isopropoxide has been obtained from NMR, MS, and DFT studies and has been used to interpret the results in the use of these reagents for diastereoselective coupling of imines. Coupling of, for example, A-benzylideneaniline gives exclusively the ( )-diamine product, with no meso-isomer. A trimeric biradical intermediate is proposed.  

Noyori, R. In Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994. 

Comprehensive Asymmetric Catalysis, Jacobsen, E. N. Pfaltz, A. Yamamoto, H. (Eds.), Springer, BerUn-Heidelberg, 1999, Vol. 1. 

Catalytic Asymmetric Synthesis, 2nd ed., Ojima, I. (Ed.), Wiley-VCH, New York, 2000. 

Blaser, H.-U. Malan, C. Pugin, B. Spindler, F. Steiner, H. Studer, M. Adv. Synth. Catal. 

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In both cases, the hydride ion approaches the double bond from the sterically more accessible side of the molecule. Reduction of imines by metals and acids, electrolytically or by formic acid gives saturated secondary amines (38,255). 

Another example for the use of hydrogen as reductant is observed in the reduction of imine [5b]. New imine reductase activity has been discovered in the anaerobic bacterium Acetobacterium woodii by screening a dynamic combinatorial library of virtual imine substrates, using a biphasic water-tetradecane solvent system. 

Reduction of imines, hydrazones, or other compounds containing the... 

Scheme 9.16 Ru-catalysed reductions of imines with A -sulfonylated 1,2-dipheny-lethylenediamine ligands.

As with hydrogenation, hydrogen transfer of imines is a poorly developed field.126-130 However, recent arene-Ru11 systems bearing chiral 1,2-diamine co-ligands have been found to be excellent catalysts for asymmetric reduction of imines with formic acid as donor.31,131-134... 

Pojer, P.M. (1979) Reduction of imines and cleavage of oximes by sodium dithionite. Aust. J. Chem. 32, 201-204. 

Various chiral ligands with metal catalysts can be employed in the organosilane reduction of imines to amines. Many of these provide modest success. These include (oxazolino)diphenylphosphinoferrocene ligands with ruthenium,605 (—)-DIOP/Rh(I),606,607 3,3 -BINOL (l,l -bi-2-naphthol) and LiHMDS,608 and (S)-phenyl V-formylprolinamidc with trichlorosilane.609... 

As an extension of the asymmetric hydrogenation of prochiral ketones to enantiomerically enriched alcohols, the reduction of imines has been a topic of interest in obtaining chiral amines of high enantiomeric purity. Several entries to enantiomerically enriched amines based on the approaches outlined above are available. These asymmetric hydrogenations have proved to be more difficult than those for prochiral ketones, but nevertheless show good promise. 

TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES (Continued)... 

Supplemental References for Table 23. Organosilane Reduction of Imines... 

The hydrosilylation- hydrolysis route is also effective for reduction of imines ( C=N—) to amines (see also Section III,A,4). The RhCl(PPh3)3... 

The preparation of chiral isoquinoline derivatives continued to be investigated. Sulfanamide 59 was prepared by addition of a lateral lithiated o-toluonitrile with the corresponding sulfinimine. Treatment of 59 with MeLi followed by acidification afforded cyclic imine 60. Reduction of imine 60 with liAlHi/MejAl afforded the trans-1,3 derivative, and... 

Saaby S, Knudsen KR, Ladlow M, Ley SV (2005) The Use of a Continuous Flow-Reactor Employing a Mixed Flydrogen-Liquid Flow Stream for the Efficient Reduction of Imines to Amines. Chem Commun 23 2909-2911 Seebach D, Overhand M, Kilhnle FNM, Martinoni D, Oberer L, Hommel U, Widmer H (1996) Beta-Peptides Synthesis by Arndt-Eistert Homologation with Concomitant Peptide Coupling. Structure Determination by NMR and CD Spectroscopy and by X-ray Crystallography. Helical Secondary Structure of a Beta-Hexapeptide in Solution and its Stability Towards Pepsin. Helv Chim Acta 79 913-941... 

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