Hydrosilylation of ketimines

The nucleophilic activation of hydrosilanes as HSi(OR)3 offers an opportunity to transfer one hydride on the carbon of ketones or imines [22]. The enantioselective organocatalytic hydrosilylation of ketones was first reported in 1999 by Matsu-mura et al. [23], the catalyst employed being a proline derivative 19 (Scheme 11.7). Amide 20 was also able to catalyze the hydrosilylation of ketimines, as indicated in Scheme 11.7 [24]. Improved results were recently reported by Kocovsky and Maikov [25], who prepared from valine some acyclic analogues of prolina-... 

Asymmetric hydrosilylation of ketimines in the presence of a chiral titanocene difluoride is improved by a nucleophilic additive (e.g., isobutylamine) which serves to release the chiral amine products and thereby generates less hindered amido complexes which are susceptible to reaction with the hydrosilane. ... 

With the increasing interest in developing catalysts able to be easily separated from the final product, many efforts have been devoted to the preparation of immobilized structures (for reviews on polymer-supported organocatalysts, see [201—204], for a more recent example, see also [205]). In this field, Kocovsky s group has also reported interesting Lewis base supported catalysts for the efficient asymmetric hydrosilylation of ketimines with silane 2. The first reported example was an N-methylvaline-derived Lewis basic formamide anchored to a polymeric support with... 

Wang Z, Wei S, Wang, C, Sun, J. Enantioselective hydrosilylation of ketimines catalyzed by Lewis basic C2-symmetric chiral tetraamide. Tetrahedron Asymm. 2007 18 705-709. 

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. 

Asymmetric hydrosilylation of several AT-alkyl ketimines with PMHS was effectively promoted by the chiral titanocene catalyst (S)-ll (Scheme 8) [24,25], The... 

Alkyl aryl ketimines were reduced with up to 99% ee (Scheme 8) [24]. The high enantioselectivity was not affected by the E Z ratio of the imines. For example, a 1.8 1 E Z mixture of the N-propylimine of 4 -methoxy-3-methyIbuty-rophenone was converted to the desired product in 97% optical yield. Hydrosilylation of the N-propylimine of cyclohexyl methyl ketone with a substrate to Ti molar ratio of 2,000 1 was completed to give the product in 98% ee [24]. N-Benzylimine of 2-octanone, a simple aliphatic ketimine, was reduced with 69% optical yield. The reduction of W-benzyl-l-indanimine gave the corresponding amine in 92% ee (Scheme 9) [24]. 

Enantioselective Hydrosilylation of C=N Double Bonds in Ketoximes and Ketimines. Homogeneous enantioselective hydrosilylation of prochiral alkyl aryl ketoximes has been carried out by using a Rh-(R,R)-NORPHOS catalyst. Thus, hydrosilylation of r-butyl phenyl ketoxime in the presence of [Rh(COD)Cl]2-(R,R)-NORPHOS followed by aqueous acidic work-up afforded the corresponding amine (eq 3) [16.5% ee, (5)], which became inverted to 15.0% ee (R) when this reaction was performed in the presence of added ammonium hexafluo-rophosphate (RhiNHaPF = 1.1, CH2CI2 solvent). ... 

Similar enantioselective hydrosilylation of isopropyl m-tolyl ketimine afforded the corresponding (7 ) amine in 50% chemical yield but with only 1.5% ee (eq 4). By way of contrast, the corresponding hydrosilylation reaction, when performed in the presence of [Rh(COD)Cl]2-l, produced the same (R)- amine in 60% chemical yield and with 13.8 1.1% ee. ... 

Lanthanide(ll)-imine complexes, obtained by reduction of aromatic ketimines with samarium and ytterbium metal, effectively catalyze the hydrosilylation of imines. The proposed catalytic cycle for the imine hydrosilylation is outlined in Scheme 279.961 1033... 

Some recent work has been directed towards the use of organocatalysts, in particular Lewis basic pipecolinic formamides, in the asymmetric hydrosilylation of N-arylimines. These catalysts function by activating the silane and exhibit broad substrate scope. For example formamide (3.186) effects enantioselective hydrosilylation of aryl-derived ketimines along with isopropyl-substituted imine (3.187) and a,P-unsaturated imine (3.188). 

To improve upon the selectivity of the ketimine reduction process further, the hydrosilylation of a range of substrates derived from (/ )- -phenylethylamine were examined [37]. Optimization of the reaction conditions allowed obtaining complete diastereoselective reduction of a wide range of acetophenone-derived ketimines as well as a-imino esters, demonstrating the cooperative effect of catalyst and the (/ )-methyl benzyl residue at the imine nitrogen. In this context, we reported also a low cost protocol for a highly stereoselective reduction of ketimines bearing a very cheap and removable chiral auxiliary, promoted by an achiral inexpensive Lewis base, such as DMF [38]. 

PMHS). One example of these reactions is shown in Equation 16.38d. These reactions have also been extended to highly enantioselective hydrosilylations of N-phosphoryl aryl ketimines (Equation 16.38e). ... 

Maikov AV, Stewart Liddon AJP, Ramirez-Lopez P, Bendova L, Haigh D, KoCovsky P. Remote chiral induction in the orga-nocatal)4ic hydrosilylation of aromatic ketones and ketimines. Angew. Chem. Int. Ed. 2006 45 1432-1435. 

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)... 

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. 

A wide range of imines undergoes hydrosilylation with PMHS in the presence of catalytic amounts of butyltris(2-ethylhexanoate)tin (245). JY-Tosyl aldimines and ketimines were efficiently reduced to tosylamides in the presence of catalytic amount of lithium methoxide. Benzaldimines and ketimines undergo efficient hydrosilylation with HSiMe2Ph in the presence of BlCeFsla (246). 

In their efforts to develop new organocatalysts, Burke and coworkers have also studied the CuAAC reaction for the synthesis of new 1,2,3-triazole-cinchona catalysts (Scheme 9.22) (P.C. Barrulas, L. Alves, A.J. Burke, unpublished results) [60]. They were screened in a variety of benchmark catalytic reactions such as the ketimine hydrosilylation with HSiClg, Michael addition reactions, and the... 

Following the pioneering discovery by Oi and Inoue on the diarylation of imines [43], improved diarylation of imines was reached in NMP using a Ru(II)/KOAc/ PPhs catalytic system for aldimines and Ru(ll)/2 KOAc without PPhs but for longer time for ketimines. The diarylated imines could be reduced into bulky amines by catalytic hydrosilylation with the same Ru(ll) catalyst. Thus the overall reaction could be performed in two steps via sequential Ru(ll) catalysed C-H bond functionalization/hydrosilylation [(Eq. 19)] [84]. 

An A-pivaloyl-L-prolineanilide promotes high-yield imine hydrosilylation by HSiCl3 with up to 93% ee. a-Deuterated amines have been formed with up to 99% ee by chi- Q ral phosphoric-acid-catalysed enantioselective transfer of deutaium from 2-deuterated benzothiazoline to ketimines the isotope effect suggests that C—D bond cleavage is rate determining. 0... 

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