Catalytic 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. 

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. 

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]. 

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]. 

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. 

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

Our proposed transition state model for this catalytic enantioselective cyanosilylation of ketone is shown as 35.30a The titanium acts as a Lewis acid to activate the substrate ketone, while the phosphine oxide acts as a Lewis base to activate TMSCN. The intramolecular transfer of the activated cyanide to the activated ketone should give the ( )-cyanohydrin in high selectivity. The successful results described above clearly demonstrate the practicality of our asymmetric catalyst for cyanosilylation of ketones. 

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 basic character of lanthanide alkoxides such as Lu3(Of-Bu)9 seem to effect aldol, cyanosilylation, aldol, and Michael reactions [111]. Complexes 2 and 22, abbreviated as LnMB (Ln = lanthanide, M = alkali metal, B = BR IOL) [112] were thoroughly studied in the catalytic, asymmetric nitroaldol reaction (Henry reaction eq. (10)) [113]. 

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-... 

To avoid the intrinsic instability of cyanohydrins and their silyl ether, Saa and coworkers reported catalytic asymmetric cyanophosphonylation reaction of aldehydes with commercially available diethyl cyanophosphonate [58]. In these works, Lewis acid-Lewis base bifunctional catalyst (65) prepared by mixing BI-NOLAM ligand with amino arms as Lewis base and Et2AlCl was found to work nicely (Scheme 6.46). Since a strong positive nonlinear effect was observed in this reaction, actual catalyst is in equilibrium with some oligomeric species of the aluminum complexes. Bifunctional catalyst (65) could also catalyze cyanosilylation of... 

Systematic investigations of the catalyst structure-enantioselectivity profile in the Mannich reaction [72] led to significantly simplified thiourea catalyst 76 lacking both the Schiff base unit and the chiral diaminocyclohexane backbone (figure 6.14 Scheme 6.88). Yet, catalyst 76 displayed comparable catalytic activity (99% conv.) and enantioselectivity (94% ee) to the Schiff base catalyst 48 in the asymmetric Mannich reaction of N-Boc-protected aldimines (Schemes 6.49 and 6.88) [245]. This confirmed the enantioinductive function of the amino acid-thiourea side chain unit, which also appeared responsible for high enantioselectivities obtained with catalysts 72, 73, and 74, respectively, in the cyanosilylation of ketones (Schemes 6.84 and 6.85) [240, 242]. 

The asymmetric catalytic cyanosilylation of aldehydes229 and the alkylation of aldehydes with ZnEt2230 using the chiral cyano binaphthol complex Ti(CN)2(i )-BINOL have been developed. 

Styryl-functionalized vanadyl(lV) salen covalently anchored onto mercapto-modifled ACs and SWCNTs showed high catalytic activity in the cyanosilylation of benzaldehyde with substrate conversion of 83 and 93%, respectively [91]. The SWCNTs were shown to be more suitable support for the VO complex relative to the high-surface-area AC, because the latter support exhibited some adventitious activity. The asymmetric version of the reaction was also performed using the chiral vanadyl complex the SWCNTs also behaved as a better support, as the %ee was 66%, whereas for AC the %ee was 48% [91]. The VO(IV) complex immobilized onto SWCNTs was also tested in the catalytic cyanosilylation of hexanal and 4-fluorobenzaldehyde with high substrate conversions 97 and 96%, respectively. 

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