Imines with trichlorosilane reductant

Reduction of Imines with Trichlorosilane Catalyzed by Chiral Lewis Bases... 

More recently, in organocatalysis, Kocovsky [69] has reported asymmetric reduction of imine with trichlorosilane catalyzed by an (A-methylvaline)-derived formamide anchored to a polymer. Under the best conditions, with 15 mol% of the catalyst enantiomeric excesses were about 85% and the catalyst could be reuse. 

After the methodology for asymmetric reduction of imines with trichlorosilane employing model substrates had been firmly estabhshed, the focus of research in the field gradually shifted towards the synthesis of functionahzed chiral amines, which represent important building blocks for pharmaceutical, agricultural, and fine chemical industries. 

P. and Stoncius, S. (2010) Reduction of imines with trichlorosilane catalyzed by chiral Lewis bases, in Chiral Amine Synthesis (Methods, Developments and Applications) (ed. T. Nugent), John Wiley Sons, Ltd, Chichester, p. 131 ... 

Scheme 42.38 Asymmetric sequential reduction of imines with trichlorosilanes catalyzed by ephedrine-based picolinamides.

Onomura O, Kouchi Y, Iwasaki F, Matsumura Y. New organic activators for the enantioselective reduction of aromatic imines with trichlorosilane. Tetrahedron Lett. 2006 47 3751-3754. 

Maikov AV, Vrankova K, StonCius S, KoCovsky P. Asymmetric reduction of imines with trichlorosilane, catalyzed by siga-mide, an amino acid-derived formamide scope and limitations. J. Org. Chem. 2009 74 5839-5849. 

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... 

Next, a few examples of asymmetric reductions with trichlorosilane are presented. An asymmetric reduction of ketones and imines was reported by Matsumura and coworkers by using trichlorosilane as reductant and A-formyl pyrrolidine derivative 36 as ligand (Scheme 28) [101, 102]. 

Formamides derived from L-pipecolinic acid act as Lewis base organocatalysts for reduction of A-arylimines with trichlorosilane, giving yields and ees in the high 90s for a wide range of imine substrates.54... 

Table 7.7 Asymmetric reduction of imines 80 with trichlorosilanes catalyzed by chiral amides (10 mol%) derived from cyclic amino acids in CH2CI2 (Scheme 7.18 and Fig. 7.4) [3c, 79, 81, 82],...

Table 4.7 Synthesis of esters of a substituted 3 amino acids 40 by reduction of enamines/imines 38/39 with trichlorosilane, catalyzed by Sigamide 35 (Scheme 4.4). ...

The experiments reported by Malkov and Kocovsky [12h] and by Sun [lla,b,e,f], indicate that the Lewis base catalyzed imine reduction with trichlorosilane is not affected by isomeric nonhomogeneity of the starting imines. Thus, for example, imines 9h-9j, which exist as 5 2 to 5 3 E/Z mixtures, were reduced to the corresponding amines with 94 97% ee (Table 4.5, entries 8 10). Appar ently, traces of HCl, naturally present in the moisture sensitive Cl3SiH, trigger an E/Z equilibration of imines 6-10, which is faster than the reduction (Scheme 4.5). 

Table 15.8 Asymmetric reduction of imines 106 derived from aromatic amines with trichlorosilanes catalyzed by chiral Lewis bases 110,112-115,118, and 120-124 (Scheme 15.25 and Figures 15.5 and 15.6).

Next to be investigated were the members of the homologous series, namely, P-imino nitriles 133 and P-imino esters 134, existing predominantly in the conjugated enamine forms 131 and 132, which cannot be reduced with trichlorosilane (Scheme 15.27) [97d]. However, Maikov and Kocovsky found that Bronsted acids can facilitate the enamine-imine equiUbrium and provide sufficient concentration of the desired imine form, whose reduction can now be accomphshed. In the case of Sigamide 114b, acetic acid (1 equiv) was identified as an optimal additive the reduction, carried out in its presence, afforded the expected P-amino nitriles 135 and P-amino esters 136 in high yields and enantioselectivities (Table 15.12, entries 1 and 2). 

In 2009, the imidazole-derived Lewis base catalyst 92, which was prepared by Jones et al., was employed for the reduction of ketimines with trichlorosilane as the reducing agent Interestingly, low catalyst loading (as low as 1% mol) works well for this reduction (entry 13, Table 32.1) [57]. During their studies, the authors found that 92 is able to selectively reduce the imine while it is inactive for ketones. Therefore, in 2011, the same group developed an asymmetric reductive amination of ketones 16 catalyzed by 92 with trichlorosilane as the hydride donor (Scheme 32.19). However, the yields for the threealkyl ketimines, a two-step, one-pot procedure plus microwave irradiation is needed to secure a useful synthetic yield [60]. 

Iwasaki F, Onomura O, Mishima K, Kanematsu T, Maki T, Matsumura Y. First chemo- and stereoselective reduction of imines using trichlorosilane activated with /V-formylpyrroli-dine derivatives. Tetrahedron Lett. 2001 42 2525-2527. 

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