Ketimines trichlorosilane

A new, metal-free protocol involving (heteroaryl)oxazoline catalysts for the enantioselective reduction of aromatic ketones (up to 94% ee) and ketimines (up to 87% ee) with trichlorosilane has been developed. The reaction is characterized by an unusual, long-ranging chiral induction.The enantiodifferentiation is presumed to be aided by aromatic interactions between the catalyst and the substrate.360 Asymmetric reduction of A-arylketimines with trichlorosilane is catalysed by A-methyl-L-amino acid-derived Lewis-basic organocatalysts with high enantioselectivity (up to 92% ee) 61... 

Not surprisingly, chiral formamides emerged as prime candidates for the development of an asymmetric variant of this reaction. A selection of the most efficient amide catalysts based on amino acids is shown in Figure 7.4 representative examples of enantioselective hydrosilylation are collected in Tables 7.7 and 7.8. Proline-derived anilide 82a and its naphthyl analogue 82b, introduced by Matsu-mura [3c], produced moderate enantioselectivity in the reduction of aromatic ketimines with trichlorosilane at 10 mol% catalyst loading (Table 7.7, entries 1 and 2). Formamide functionality proved to be crucial for the activation of the silane, as the corresponding acetamides failed to initiate the reaction. 

Lu SM, Han XW, G Zhou Y (2004) Adv Synth Catal 346 909 Maikov AV, Mariani A, MacDougall KN, Koevsky P (2004) Role of nonco-valent interactions in the enantioselective reduction of aromatic ketimines with trichlorosilane. Org Lett 6 2253-2256 Martin NJA, List B (2006) J Am Chem Soc 128 368... 

Table 4.1 Reduction of ketimines 6a and 6b with trichlorosilane (Scheme 4.2), catalyzed by formamides 16 21 (Figure 4.1).

Table4.11 Reduction of ketimines 6 with trichlorosilane, catalyzed by the valine derived N methyl formamides (S) 23, (S) 48 52 ...

Maikov, Kocovsky, and co-workers have developed different L-valine-based Lewis basic catalysts such as 81 [176, 177], for the efficient asymmetric reduction of ketimines 76 with trichlorosilane 2, or catalyst 82 [178] with a fluorous tag, which allows an easy isolation of the product and can be used in the next cycles, while preserving high enantioselectivity in the process. Sigamide catalyst 83 [179, 180] and Lewis base 84 [181] were employed in a low amount (5 mol%) affording final chiral amines 80 with high enantioselectivity (Scheme 30) [182]. Interestingly, 83 was used for the enantioselective preparation of vicinal a-chloroamines and the subsequent synthesis of chiral 1,2-diaryl aziridines. In these developed approaches the same absolute enantiomer was observed in the processes. 

Trichlorosilane as the Reducing Reagent 957 Table 32.1 Reduction of ketimines by trichlorosilane. 

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]. 

The group of Benaglia reported a sequential reduction of ketimines that worked with trichlorosilane (169) as the reducing agent (Scheme 42.38). Furthermore, picolinamides of ephedrine 108a,b turned out to be viable catalysts for the direct enantioselective reductive amination starting from ketone 167 and anihne (168) [87]. 

As mentioned, Matsumura published the first asymmetric reduction of ketimines with a proline formamide activator A 1 and trichlorosilane. The yield and selectivities were only moderate, but it paved the way for further developments. They showed that it was possible to reduce imines selectively in the presence of ketones without affecting the latter. Additionally, a transition state explaining the stereoinduction was hypothesized (Figure 32.6). Transition state TS 1 is preferred over TS 2 because of the steric phenyl-phenyl repulsion of the activator and the substrate. This explains the need of aryl imines for successfid stereoinduction. 

Gautier F-M, Jones S, Martin SJ. Asymmetric reduction of ketimines with trichlorosilane employing an imidazole derived organocatalyst. Org. BiomoL Chem. 2009 7 229-231. 

Maikov AV, Mariani A, MacDougall KN, Kocovsky P. Role of noncovalent interactions in the enantioselective reduction of aromatic ketimines with trichlorosilane. Org. Lett. 2004 2 2253 2256. 

Zheng H, Deng J, Lin W, Zhang, X. Enantioselective hydrosilylation of ketimines with trichlorosilane promoted by chiral iV-picolinoylaminoalcohols. Tetrahedron Lett. 2007 48 7934-7937. 

A well-defined iron hydride complex FeH(CO)(NO)(Ph3P)2 is highly active as a catalyst for selective hydrosilylation of internal alkynes to vinylsilanes. Depending on the silane employed, either E- or Z-selective hydrosilylation products are formed in excellent yields and good to excellent stereoselectivities. The stereochemical course of this transformation is dependent on the steric demand of the substituents on the silane. " A new 0 family of Lewis-basic 2-pyridyloxazolines catalyses the enantioselective reduction of prochiral aromatic ketones and ketimines using trichlorosilane. 1-Isoquinolyloxazoline (20) derivative was identified as the most efficient catalyst of the series capable of delivering high enantioselectivities in the reduction of both ketones (up to 94% ee) and ketimines (up to 89% (p)... 

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