Amines from imines hydrosilylation

Induction of chirality can be observed when a chiral catalyst is used for the hydrosilylation of a ketone [84]. Similarly, optically active amines (50% e.e.) can be obtained from imines [85]. 

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... 

Preparation of enantiomerically pare secondary amines by catalytic asymmetric hydrogenation or hydrosilylation of imines is as important as the preparation of alcohols from ketones. However, asymmetric hydrogenation of prochiral ON double bonds has received relatively less attention despite the obvious preparative potential of this process.98... 

While hydrosilylation of imines is known to be effected by rhodium catalysts3, nickel catalysts prepared in situ from Ni(0Ac)2 4H20 and thiosemicarbazones are also found to promote the reactions of iV-substituted imines with HSiEt3 in dry DMSO at 35 °C, giving the corresponding secondary amines in excellent yields after basic work-up (equation 77)185. 

Asymmetric hydrosilylation of imines affords synthetically useful optically active sec-amines, but study on this subject is still quite limited [8 c]. Uemura and co-workers applied their Rh(I)-2 catalytic system to two imines [6]. A good result was obtained from N-phenyl-l-phenylpropanimine (up to 53% ee), but the reaction with the M-benzyl analogue gave low selectivity (up to 11 % ee). 

Hydrosilylation of unsaturated organic molecules is an attractive organic reaction. Asymmetric hydrosilylation of prochiral ketones or imines provides effective routes to optically active secondary alcohols or chiral amines (Scheme 756). These asymmetric processes can be catalyzed by titanium derivatives. The ( A ebthi difluoro titanium complex has been synthesized from the corresponding chloro compound.1659 This compound results in a very active system for the highly enantioselective hydrosilylation of acyclic and cyclic imines and asymmetric hydrosilylation reactions of ketones including aromatic ketones.1661,1666,1926-1929 An analogous l,l -binaphth-2,2 -diolato complex catalyzes the enantioselective hydrosilylation of ketones.1... 

The sequential hydroamination/hydrosilylation reaction (Scheme 54) catalyzed by 143 and 144 was also investigated. In the first step, aminoalkynes were converted to cyclic imines by hydroamination reaction and the subsequent hydrosilylation led to the corresponding silicon species. Hydrolysis of the products gave cyclic amines similar to the ones obtained from the hydroamination of aminoalkenes. However, the starting materials in the sequential hydroamination/hydrosilylation reaction were aminoalkynes. Therefore, the reactions are faster and easier to perform. 

Since CIgSiH is known to be activated by DMF and other Lewis bases to effect hydrosilylation of imines (Scheme 4.2) [8], it is hardly surprising that chiral formamides, derived from natural amino adds, emerged as prime candidates for the development of an asymmetric variant of this reaction [8]. It was assumed that, if successful, this approach could become an attractive altemative to the existing enzymatic methods for amine production [9] and to complement another organo catalytic protocol, based on the biomimetic reduction with Hantzsch ester, which is being developed in parallel [5]. 

In the case of the hydrosilylation of C=N bonds, extremely high levels of enantioselectivity were dramatically realized by use of the (tetrahydroinde-nyl)titanium(IV) fluoride T4 (Fig. 12) by Buchwald in 1996 [55]. The in situ catalyst uniquely derived by mixing the titanocene fluoride T4 (1.0-0.02 mol %) with phenylsilane PhSiHj (1.5 eq referred to ketone) as hydrogen atom donor reduces the imines 13-17 (Fig. 13) to the amines A3-A7 in 80-96% yields (Table 3). An alternative activation method for the titanocene by addition of methanol and pyrrolidine was also described. In this case, the imine from acetophenone and methylamine, 13, was converted at room temperature to 35 °C to give the corresponding secondary amine in 94-95% yield with 97-99% ees (S). Moreover, alkylimines were also reduced in 92-99% ees. 

Much work has also been conducted on the hydrosilylation of ketones and imines (Equation 16.16). The products from these reactions are silyl ethers and sdylamines. These additions of silanes across C-X ir-bonds have been conducted predominantly for the purpose of generating optically active alcohols and amines after hydrolysis. Because the mechanism of these reactions is less defined than the mechanism of alkene hydrosilylation, and this chemistry lies outside the theme of this chapter, the hydrosilylation of ketones and imines is presented only briefly. Instead, this chapter provides an overview of the scope and motivation for the hydrosilylation of alkenes and alkynes and provides details on the mechanisms of these reactions catalyzed by complexes of various metals. Several comprehensive reviews of the scope of these reactions have been published. ... 

Part two (section 3) deals with the hydrosilylation of unsaturated carbon-heteroatom bond, mostly 0=0 and 0=N (but also C N, and C=S), as a catalytic method for the reduction of C=0 and C=N bonds—one of the most fundamental transformations in organic chemistry. Catalytic hydrosilylation of prochiral ketones and imines with substituted silanes and siloxanes that can provide (if followed by hydrolysis) convenient access to chiral alcohols and amines, respectively, discussed from the catalytic and synthetic point of view completes this part. 

Buchwald reported an important advance in enantioselective C=N reductions with the chiral titanocene catalyst 186 (X,X = l,l -binaphth-2,2 -diolate) [137]. The reduction of cyclic imines with 186 and silanes afforded products with high selectivity however, reductions of acyclic imines were considerably less selective. It was suggested that this arose from the fact that, unlike cyclic imines, acyclic imines are found as mixtures of equilibrating cis and trans isomers. An important breakthrough was achieved with the observation that in situ activation of the difluoride catalyst 187 (X = F) gave a catalytically active titanium hydride species that promotes the hydrosilylation of both cyclic and acyclic amines with excellent enantiomeric excess [138]. Subsequent investigations revealed that the addition of a primary amine had a beneficial effect on the scope of the reaction [138, 139]. A demonstration of the utility of this method was reported by Buchwald in the enantioselective synthesis of the alkaloid frans-solenopsin A (190), a constituent of fire-ant venom (Scheme 11.29) [140]. 

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