Cyanohydrin silyl ethers

Indole-3-carboxaldehydes gave the corresponding cyanohydrin silyl ethers 137 upon heating with trimethylsilyl cyanide in acetonitrile or DME. After subsequent oxidation with DDQ, good yields of the carbonyl nitriles 138 were obtained, also providing a mild new route for the parent system 138 (R1 = R2 = H). Further elaboration provided the imidates 139, which participated in a reaction with tryptophan esters to give moderate yields of the marine alkaloids rhopaladins A-D <02T2813>. 

Cyanosilylations of carbon-oxygen and carbon-nitrogen double bonds with cyanosilanes are very important synthetic reactions since the products, cyanohydrin silyl ethers and a-amino nitriles, serve as synthetic intermediates for a variety of natural products. A number of studies on these subjects have been reported in the last decade however, this review does not deal with carbonyl and imine cyanosilylations due to the availability of recent reviews and limited... 

Trimethylsilyl)benzophenone cyanohydrin has been prepared previously by the addition of trimethylsilyl cyanide to benzophenone using an aluminum chloride catalyst.4 The preparation of cyanohydrin silyl ethers described in the synthesis is based on... 

OL-Keto esters. The cyanohydrin silyl ether < 1) of methyl glyoxylate (4, 542-543 5, 720) can be converted by alkylation of the anion into the enol acetate (2) of a-keto esters. 

TrialkylsUyl cyanides, which also possess sp C—Si bonds, react with carbonyls. Znh, " AlCb, TMSOTf, LnCb (Ln = La, Ce, Sm), etc., are employed as the promoter, and cyanohydrin silyl ethers are obtained in high yields even from hindered ketones (equation 12). The products are converted to various synthetically important intermediates such as cyanohydrins, a,p-unsaturated nitriles or amino alcohols. 

Conversion of aldehydes to ketones via cyanohydrin, derivatives (ethers) by alkylation or Michael addition also via cyanohydrin silyl ethers, or via a-dialkylaminonitriles (see also Stetter reaction), (see 1st edition). 

Special preparations. a-Trialkylsiloxy aldehydes and l-tosyloxy-2-alkanols have been synthesized using DIBALH reduction of cyanohydrin silyl ethers and epoxy tosylates, respectively. Indoles and (Z)-allylic alcohols are acquired after simple manipulations of the primary reduction products of nitriles and a-hydroxy esters, respectively. 

Cyanosilylation of carbonyl compounds. The formation of cyanohydrin silyl ethers is catalyzed by the Fe-montmorillonite. Enones undergo 1,4-addition. 

As base. In the absence of solvent KF promotes the condensation of trimethyl-silylacetonitrile with aldehydes to give the /3-cyanohydrin silyl ethers. With micro-wave as energy source the reaction is complete within minutes. KF in the presence of 18-crown-6 successfully effects the Michael reaction between a-acetamidomalonic esters and propynoic esters also. 

Addition to hindered ketones. With ZnU as catalyst the formation of cyanohydrin silyl ethers using either t-butyldimethylsilyl or t-butyldiphenylsilyl cyanide is remarkably efficient. 

Cyanohydrin silyl ethers Yttrium isopropoxide-more likely, the ((-PrO),3Y50 species—complexes with l,3-bis(2-methylferrocenyl)propane-l,3-dione (1) to afford a highly efficient catalyst for the asymmetric silylcyanation of electron-rich aromatic aldehydes with MCjSiCN. 

Pro-azaphosphatrane lb is an effective catalyst for the addition of tri-methylsilyl cyanide to aldehydes and ketones under mild conditions, giving rise to cyanohydrins and cyanohydrin silyl ethers, respectively, in moderate to high yields, Eqs. (24) and (25) [149]. 

Trimethylcyanation of both aromatic and aliphatic ketones in the presence of lb proceeded smoothly at room temperature to give the corresponding cyanohydrin silyl ethers in moderate to high yields. a,j8-Unsaturated ketones gave 1,2-addition products regioselectively, and no 1,4-adducts were detected. With 4-t-butylcyclohexanone and (- )-menthone, yields were high but diastere-oselectivity was poor. With (ll )-(-F)-camphor, however, the yield was low but diastereoselectivity was excellent. 

The 1,2-addition of a cyanide ion to a carbonyl compound to form a cyanohydrin is a fundamental carbon-carbon bond-forming reaction in organic chemistry, and has frequently been at the forefront of advances in chemical transformations. In 2000, Belokon and North developed a catalytic system based on a vanadium-salen complex (Scheme 9.1). The synthesis of vanadium(iv) complex 1 was accomplished by refluxing a mixture of the corresponding Schiff base with vanadium(iv) sulfate and pyridine in ethanol under an argon atmosphere. A very low catalyst loading of 0.1 mol% was employed to convert aromatic and aliphatic aldehydes to cyanohydrin silyl ethers 3 with enantioselectivities of 68-95% after 24 h. Further investigations... 

Shibasaki and Kanai have also reported bifunctional asymmetric catalyst (66) derived from carbohydrates (Scheme 6.47) [61]. Compared to BINOLate type catalyst (64a), generally, the enantiomeric excess values of resultant cyanohydrin silyl ethers were not higher. The reaction proceeded with high enantiomeric excess without both slow addition of TMSCN and the use of external phosphine oxide as an additive. 

Silyl cyanides react enantioselectively with such electrophiles as aldehydes, ketones, imines, activated azines, or,/ unsaturated carbonyl compounds, epoxides, and aziridines in the presence of chiral Lewis acid catalysts to give functionalized nitriles, versatile synthetic intermediates for hydroxy carboxylic acids, amino acids, and amino alcohols (Tables 3-6, 3-7, 3-8, and 3-9, Figures 3-6, 3-7, and 3-8, and Scheme 3-154). ° Soft Lewis acid catalytst, the reaction of epoxides with trimethylsilyl cyanide often leads to isonitriles, which are derived from silylisonitrile spiecies (Schemes 3-155 and 3-156). Soft Lewis base such as phosphine oxide also catalyzes the reaction and cyanohydrin silyl ethers of high ee s are isolated. 

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