Hydrosilylation imine substrates

A catalytically active chiral hydridotitanium complex obtained from (5,5j-ethylene(T -tetrahydroindenyl)titanium difluoride and PhSiHj hydrosilylates imines under mild conditions with significantly higher substrate catalyst ratios than known methods yield. ... 

The discussion of the activation of bonds containing a group 15 element is continued in chapter five. D.K. Wicht and D.S. Glueck discuss the addition of phosphines, R2P-H, phosphites, (R0)2P(=0)H, and phosphine oxides R2P(=0)H to unsaturated substrates. Although the addition of P-H bonds can be sometimes achieved directly, the transition metal-catalyzed reaction is usually faster and may proceed with a different stereochemistry. As in hydrosilylations, palladium and platinum complexes are frequently employed as catalyst precursors for P-H additions to unsaturated hydrocarbons, but (chiral) lanthanide complexes were used with great success for the (enantioselective) addition to heteropolar double bond systems, such as aldehydes and imines whereby pharmaceutically valuable a-hydroxy or a-amino phosphonates were obtained efficiently. 

Asymmetric hydrosilylation of the cyclic imine 17 (Approach A) was precedented on simpler substrates by Buchwald but the method requires an expensive and highly air-sensitive chiral htanocene catalyst (Scheme 8.5) [6]. 

As outlined in Section II,E, ketone and imine groups are readily hydrogenated via a hydrosilylation-hydrolysis procedure. Use of chiral catalysts with prochiral substrates, for example, R,R2C=0 or R,R2C=N— leads to asymmetric hydrosilylation (284, 285 Chapter 9 in this volume) and hence optically active alcohols [cf. Eq. (41)]. 

Transition metal-catalyzed hydrosilylation, an established route for transformations of unsaturated carbon substrates, is also well known for reactions of nitriles,183 imines,184 and oximes.185 Work in this area includes the Co2(CO)8-catalyzed addition of trialkylsilanes to aromatic, aliphatic, and a,/3-unsaturated nitriles, giving /V,/V-bis(silyl)amines and/or -enamines in fair to good yields [Eqs. (73) and (74)].186... 

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]. 

Several cyclic imines were reduced with phenylsilane as a reducing agent in the presence of the chiral titanocene catalyst 11 followed by a workup process to give the corresponding cyclic amines in excellent ee [26]. The hydrosilylation of 2-propyl-3,4,5,6-tetrahydropyridine with (R)-ll (substrate Ti=100 l) in THF at room temperature was completed in about 6 h (Scheme 14) [29]. The reaction mixture was treated with an acid and then with an aqueous base to afford (S)-coniine, the poisonous hemlock alkaloid, in 99% ee. 

Racemic 2,5-disubstituted 1-pyrrolines were successfully resolved by hydrosilylation with PMHS in the presence of 11. For instance, reduction of 5-methyl-2-phenyl-l-pyrroline with a five equivalents of PMHS using (R)-ll (substrate Ti=40 l) in the presence of a three equivalents of i-C4H9NH2 in THF at 70 °C followed by purification by chromatography resulted in the S unreacted imine in 98.7% ee (42% yield) and the 2R,5R amine in 98.5% ee (43% yield) accompanied by a small amount of (R)-2-methyl-5-phenyl-l-pyrroline in 98% ee (Scheme 15)... 

A neutral Ir complex consisting of [IrCl(COD)]2 and (S)-6 catalyzed the hydrosilylation of the N-methylimine of acetophenone (substrate Ir=100 l) with two equivalents of diphenylsilane in ether at 0 °C to give the S product in 89% optical yield (Scheme 17) [34]. The corresponding N-phenylimine was reduced with 23% optical yield. 2-Phenyl-1-pyrroline was reduced with the same catalyst to afford the S cyclic amine in 88% ee. The enantiomeric excess was decreased to 7% in the hydrosilylation of the corresponding 6-membered cyclic imine. 

Asymmetric hydrosilylation of prochiral carbonyl compounds, alkenes, 1,3-dienes, and imines has been extensively studied and remains one of the most important subjects in the field. This reaction is strongly affected by the nature of the catalyst (metal, type of chiral ligand) and the substrate as well as the reaction conditions (solvent, temperature, etc.). In recent years, many papers have been published on asymmetric hydrosilylation, describing new catalytic systems (mainly new optically active ligands) and new synthetic applications of the reaction [4, 24]. 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

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). 

Hydrosilylations by complexed CuH have been applied to several substrate types (Scheme 1-17). As illustrated by the following examples, the stereochemical outcomes from both 1,2-additions (to aryl ketones and aryl imines ) and 1,4-conjugate additions (cyclic ketones, P-aryl and/or P-silyl enoates, and unsaturated lactones) can be controlled by these ligand-accelerated reactions. One of the key tricks to this chemistry is to take advantage of the tolerance of CuH complexes to alcohols and water.In fact, several methods rely on the presence of a bulky alcohol (e.g., t-BuOH) to significantly enhance reaction rates. It takes relatively little added alcohol (volume-wise) to accelerate the hydrosilylation, usually on the order of 1-3 equivalents. The role of this additive is usually ascribed to the more rapid quenching of an intermediate copper alkoxide or enolate, which necessarily generates a copper alkoxide, an ideal precursor to rapid reformation of CuH in the presence of excess silane. Thus, the rate increase is presumably due to... 

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]. 

Their substrates are 2-phenylpyridines, imines, benzo[/i]quinones, phosphines, oxygen compounds, sulfur compounds, etc., as described in the previous sections or in Fig. 5.11, Tables 5.5 and 5.6. These reactions are arylations, alkenylations, alkylations, acylations, cyclizations, hydrogenations, oxidations, hydrosilylations, dehydrogenations, etc. 

Literature on the hydrosilylation of ketones and imines is extensive. This chemistry provides a method for the reduction of these unsaturated substrates with reagents that are inexpensive and either liquids or solids, rather than gases (H ). As noted in the introduction, much of this literature focuses on the enantioselective hydrosilylation of ketones and imines to form non-racemic chiral alcohols and amines. In addition to the conveniaice of using a liquid reagent, the ability to vary the substituents on a silane allows for tuning of the stereoselectivity of the reductions. 

Wang Z, Cheng M, Wu P, Wei S, Sun J. l-Piperazine-2-car-boxyUc acid derived iV-formamide as a highly enantioselective Lewis basic catalyst for hydrosilylation of iV-aryl imines with an unprecedented substrate profile. Org. Lett. 2006 8 3045 3048. 

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