Cyanosilylation asymmetric

Mori et al.149 also reported the asymmetric cyanosilylation of aldehyde with TMSCN using 132 (X = CN) as the precatalyst. The chiral dicyano complex was generated in situ, and the asymmetric cyanosilylation gave ee values of up to 75%. Scheme 2-58 depicts the proposed reaction process. 

Another example is the asymmetric cyanosilylation of aldehydes catalyzed by bifunctional catalyst 131.100 Compound 131 contains aluminum, the central metal, acting as a Lewis acid, and group X, acting as a Lewis base. The asymmetric cyanosilylation, as shown in Scheme 8-50, proceeds under the outlined... 

Figure 8-6. Transition state for 131 catalyzed asymmetric cyanosilylation. 

For other catalytic asymmetric cyanosilylation of aldehydes, see C.-D. Hwang, D.-R, Hwang, B.-J. Uang, Enantioselective Addition of Trimethylsilyl Cyanide to Aldehydes Induced by a New Chiral TiflV) Complex, J. Org Chem 1998,63,6762-6763, and references tited therein. 

Y. Hamashima, D. Sawada, M. Kanai, M Shibasaki A New Bifunctional Asymmetric Catalysis An Effident Catalytic Asymmetric Cyanosilylation of Aldehydes, J. Am Chem Soc 1999,121, 2641-2642. 

The cross-linked dendritic BINOLate p-71 (20mol%) was also used as a supported catalyst in the asymmetric cyanosilylation of pivalaldehyde in CH2CI2. The catalyst was reused several times after separation from the reaction mixture by filtration. In 20 consecutive reactions, the cyanohydrine product was formed in >90% yield. Initially, an increase in enantioselectivity was observed from 72%... 

Scheme 6.85 Product range of the 73- and 74-catalyzed asymmetric cyanosilylation of ketones.

An asymmetric cyanosilylation followed by hydrolysis and cyclization has been used by Curran and co-workers as the key step in the asymmetric synthesis of camptothecin <2001JA9908, 2003F1(59)369>. 

We began our synthesis by finding the optimum reaction conditions for the catalytic asymmetric cyanosilylation of ketone 28 (Table 1). Based on previous studies,30 the titanium complex of a D-glucose derived ligand (catalyst 32 or 33) generally gives (/ )-ketone cyanohydrins, which is required for a synthesis of natural fostriecin. 

Activation of Me3SiCN by coordination of the Si to lithium BINOL-ate as catalyst has been shown to result in the enantioselective formation of cyanohydrins 73 from aromatic and heteroaromatic aldehydes with 82-98% ee (Scheme 7.15) [71]. (For experimental details see Chapter 14.5.4). Several other groups have used dual activation with a chiral Lewis acid and a non-chiral Lewis base [72]. Asymmetric cyanosilylation of PhCOMe and its congeners has also been reported to occur in the presence of sodium phenyl glycinate as catalyst, with up to 94% ee [73],... 

Asymmetric cyanosilylation of ketones and aldehydes is important because the cyanohydrin product can be easily converted into optically active aminoalcohols by reduction. Moberg, Haswell and coworkers reported on a microflow version of the catalytic cyanosilylation of aldehydes using Pybox [5]/lanthanoid triflates as the catalyst for chiral induction. A T-shaped borosilicate microreactor with channel dimensions of 100 pm X 50 pm was used in this study [6]. Electroosmotic flow (EOF) was employed to pump an acetonitrile solution of phenyl-Pybox, LnCl3 and benzal-dehyde (reservoir A) and an acetonitrile solution of TMSCN (reservoir B). LuC13-catalyzed microflow reactions gave similar enantioselectivity to that observed in analogous batch reactions. However, lower enantioselectivity was observed for the YbCl3-catalyzed microflow reactions than that observed for the batch reaction (Scheme 4.5). It is possible that the oxophilic Yb binds to the silicon oxide surface of the channels. 

The extension of this route to the case of ( )-camptothecin [61] was followed by a series of improvements [62,63], where the key intermediate 21 was obtained via the Sharpless dihydroxylation previously proposed by Fang [64] or via an asymmetric cyanosilylation reaction [65] (Scheme 16.16). 

Finally, carbohydrate ligands of enantioselective catalysts have been described for a limited number of reactions. Bis-phosphites of carbohydrates have been reported as ligands of efficient catalysts in enantioselective hydrogenations [182] and hydrocyanations [183], and a bifunctional dihydroglucal-based catalyst was recently found to effect asymmetric cyanosilylations of ketones [184]. Carbohydrate-derived titanocenes have been used in the enantioselective catalysis of reactions of diethyl zinc with carbonyl compounds [113]. Oxazolinones of amino sugars have been shown to be efficient catalysts in enantioselective palladium(0)-catalyzed allylation reactions of C-nucleophiles [185]. 

Trost and coworkers developed a chiral zinc phenoxide for the asymmetric aldol reaction of acetophenone or hydroxyacetophenone with aldehydes (equations 62 and 63) . This method does not involve the prior activation of the carbonyls to silyl enol ethers as in the Mukaiyama aldol reactions. Shibasaki and coworkers employed titanium phenoxide derived from a phenoxy sugar for the asymmetric cyanosilylation of ketones (equation 64). 2-Hydroxy-2 -amino-l,l -binaphthyl was employed in the asymmetric carbonyl addition of diethylzinc , and a 2 -mercapto derivative in the asymmetric reduction of ketones and carbonyl allylation using allyltin ° . ... 

Although HCN also adds to these unsaturated bonds to afford cyanohydrins and a-amino nitriles, use of TMSCN instead of HCN provides an efficient and safer route to these compounds. Cyanosilylation with TMSCN is accelerated by acid and base catalysts. In recent years a variety of organic and inorganic compounds have been found to work as effective catalysts, and much attention has been devoted for the development of chiral catalysts for asymmetric cyanosilylation of aldehydes, ketones, and imines. 

Inoue et al. reported that a complex prepared from AlMes and peptide Schiff base 166 is available for asymmetric cyanosilylation of aldehydes (Scheme 10.239) [630]. The enantioselectivity observed is not as high, even with a stoichiometric amount of the complex (up to 71% ee). A more recent study by Snapper and Hoveyda has, however, revealed that a similar catalyst system using Al(()t-Pr) ), and peptide Schiff base 167 is quite effective in catalytic asymmetric cyanosilylation of both aromatic and aliphatic ketones (66->98%, 80-95% ee wifh 10-20 mol% of fhe catalyst) [631]. 

Al-BINOL complex 168a, developed by Shibasaki et al., is one of the most efficient catalysts for asymmetric cyanosilylation of aldehydes (Scheme 10.239) [632]. 

In the presence of 168 a (9mol%) and a phosphine oxide (Bu),P(O) and Ph2P(O)Me for aromatic and ahphatic aldehydes, respectively, 36 mol%), slow addition of TMSCN achieves excellent enantioselectivity with a wide range of aldehydes (86-100%, 83-98% ee). The Al complex has been proposed to work as a bifunctional catalyst for dual activation of the two reactants - the Lewis acidic Al center enhances the electrophilicity of aldehydes and the Lewis basic phosphine oxide induces cyanide addition by nucleophihc activation (Scheme 10.240). This catalytic asymmetric cyanosilylation has been used for the total synthesis of epothilones [652]. 

Table 7.9 Asymmetric cyanosilylation of benzaldehyde in ionic liquids using supported VO(salen) complexes.

Mori and Inoue reported that the peptide complex of lanthanum isopropox-ide also exhibied high catalytic activity towards asymmetric cyanosilylation [58]. Although the reaction proceeded in the presence of only 1 mol % of the catalyst, the enantiolelectivity was moderate to good (up to 71% ee). Abiko recently re-... 

A catalytic asymmetric cyanosilylation of carbonyl compounds with Me SiCN using either a carbohydrate-ba.sed phosphine oxide (54) " or the monolithium salt of a chiral salen ligand " has been studied. Comparing to the BINOL analogues, the reaction involving 54 does not require phosphine oxide additives to attain high levels of asymmetric induction, the catalytic activity is higher, and Me SiCN can be introduced rapidly. 

A sugar-based catalyst for catalytic asymmetric cyanosilylation has been developed. This catalyst, 248, is derived from tri-O-acetyl-D-glucal via the intermediates shown in Scheme 39. It incorporates a Lewis acidic and a Lewis basic site within the molecule, and it was found that the conformational constraint induced by the phenyl group was necessary for good enantioselectivity. Treatment of benzaldehyde and TmsCN with catalytic quantities of 248 gave after acid hydrolysis the cyanohydrin 249 in 80% ee, and several other aldehydes behaved similarly. 

Scheme 7.14 Asymmetric cyanosilylation of benzaldadehyde using complex 18.

In 2010, Bernal, Fernandez, and Lassaletta [198] disclosed an unprecedented asymmetric cyanosilylation of nitroalkenes that was catalyzed enantioselectively by a quinine derivative with tetraalkylammonium cyanide and thiourea moieties. The activation of the nitroalkene takes place by hydrogen bonding to the thiourea, while the tetraalkylammonium cation moiety binds the cyanide anion, which is dehvered stereoselectively to the double bond. 

Scheme 124 Asymmetric cyanosilylation of ketones early in the syntheses of different members of the bisorbicillinoid family...

Tian SK, Hong R, Deng L (2003) Catalytic Asymmetric Cyanosilylation of Ketones with Chiral Lewis Base. J Am Chem Soc 125 9900... 

Scheme 19.2 Asymmetric cyanosilylation of aldehydes catalysed by Al(salen) complexes.

Scheme 19.3 Possible mechanism for asymmetric cyanosilylation of aldehydes catalysed by a bimetallic Al(salen) complex.

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