Reduction of imines to amines

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... 

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... 

Saaby, S. and Knudsen, K.R. and Ladlow, M. and Ley, S.V. (2005). The use of a continuous flow-reactor employing a mixed hydrogen-liquid stream for the efficient reduction of imines to amines. Chem. Commun., 23, 2909-2911. 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

The reduction of imines to amines (equation 21) by dissolving metals is usually carried out using active metals in a protic solvent, typically Na-alcohol, Zn-NaOH and A1 or Mg in alcohols. - ""- Although the mechanism of these reductions has not been investigated in detail it is almost certainly analogous to that of the reduction of ketones (Section 1.4.2). It has been established that radical anions are intermediates in these reductions and in the absence of a proton donor reductive dimerization is the principal reaction path. ... 

In organic acid media, NaCNBHj is converted to acyloxycyanoborohydrides whose reactivity is comparable to that of NaBH4 in CF3COOH, especially concerning the reduction of imines to amines, tosylhydrazones to saturated hydrocarbons, oximes to hydroxylamines, or reductive amination. Depending on the substrate, NaBH4 or NaCNBHj is recommended (Sections 3.3.1, 3.3.4) [GNl]. 

Silanes are widely recognized as efficient reagents for reduction of carbonyl and heterocarbonyl functionality. In the case of alkyl and arylsilanes, the reaction requires catalysis by Lewis acids or transition metal complexes 1, 3] however, with more Lewis acidic trichloro or trialkoxysilanes, an altemative metal free activation can be accomplished. Thus, it has been demonstrated that extracoordinate silicon hydrides, formed by the coordination of silanes to Lewis bases, such as tertiary amines 7a], DMF [7b] or MeCN, and so on [7], can serve as mild reagents for the reduction of imines to amines [8]. In the case of trichlorosilane, an inexpensive and relatively easy to handle reducing reagent, and DMF as a Lewis basic promoter, the intermediacy of hexacoordinate species has been confirmed by Si NMR spectro scopy [7b]. 

The lock-in of the self-assembled stmctures may be achieved by performing a chemical reaction that irreversibly links together the components of the entity represented by the optimal combination. This is the case, for instance, in the reduction of imines to amines. On the other hand, a simple change in conditions, such as temperature or pH, may slow down the con-... 

NADP+ (Figure 1.40). The mechanism of reduction of imines to amines as well as of carboxylate to aldehyde is similar to that of the reduction of ketones. 

Chemical methods for the TH of C=N bonds, and notably the reduction of imines to amines, have been known for many decades, early examples being the use of ruthenium complex Ru3(CO)i2 [20] and [RuCl2(PPh3)] [21]. In both cases, IPA was used as the reducing agent and a base was used to activate the catalyst. Relevant to the latter example, it was later demonstrated that [RuH2(PPh3)] was an active TH catalyst which did not require added base [22, 23]. 

Figure 1.6 Selected biocatalytic asymmetric reductions of imines to amines.

---