Cyanohydrin trimethylsilyl ether

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of ctir-bonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into 0-TRIMETHYLSILYL-4-METH0XYMANDEL0-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotnmethylsilane A general synthesis of allemc esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADlENOATE. 

Conjugate addition, 34-5, 51-2,53, 132, 133 Conjugate hydroxymethylation, 59-60 Copper(n) bromide, 54 Copper([) chloride, 120 Copper(n) chloride, 120 Copper(i) cyanide, 7,52, 53 Copper(i) iodide, 54 Corey s internal quench, 104 Cyanohydrin trimethylsilyl ether, 137 Cycloaddition. 34,112 Cydobutane-l,2-dione, 135 Cyclohept-2-dione, 135 Cyclohex-2-enone, 52,123 Cyclohcxa-1,3-diene, 26 Cyclohexane carboxaldehyde, 22-3,69 73,78... 

Fluoro-2-phenylacctonitriles are obtained in high yield with diethylaminosulfur trifluoride (DAST) from the corresponding cyanohydrin trimethylsilyl ethers, which were in turn obtained from substituted benzaldehydes and cyanotrimethylsilane.19 For example, 2-fluoro-2-phenyl-acetonitrile (5) is obtained from the trimethylsilyl ether 4.19... 

Asymmetric cyanation of aldehydes is important in organic synthesis. Mukaiyama and Minowa have developed a new chiral Lewis acid catalyst which is readily prepared from l,l -dimethylstannocene, triflic acid, and (+)-cinchonine [49]. In the presence of this Lewis acid reaction of TMSCN with aldehydes proceed smoothly at -78 °C in dichloromethane to give the corresponding cyanohydrin trimethylsilyl ether in high yield with good to excellent ee. In this reaction the products are isolated as trimethylsilyl ethers and the reaction proceeds smoothly in the presence of 30 mol % tin(II) Lewis acid (Eq. 31). The catalyst, Sn(II) monoalkoxymonotriflate, is assumed to be regenerated from the initially produced Sn(II) alkoxide and trimethylsilyl triflate. 

MCM-41-(CH2)3-NH-(CH2)2-NH2 was utilized for the cyanosilylation of carbonyl compounds to afford cyanohydrin trimethylsilyl ethers 98 (Scheme 3.27)," which are industrially valuable intermediates in the synthesis of cyanohydrins, (3-amino alcohols, a-amino acids and other biologically active compounds. ... 

Various aldehydes and ketones were treated with MesSiCN to furnish the corresponding cyanohydrin trimethylsilyl ethers (Table 3.8). 

The hypervalent silicon derivative 100, formed from the interaction of the more basic secondary amine group of the catalyst 99 with MesSiCN (Scheme 3.28), was assumed by the authors to produce the transition state 101 by interaction with the carbonyl compound (since the nucleophilicity of the cyano group of 100 is enhanced by electron donation from the pentavalent silicon) immediate silyla-tion gives the corresponding cyanohydrin trimethylsilyl ether 98 and restores the catalyst. 

The addition of trimethylsilylcyanide to diethyl 2-oxopropylphosphonate, catalyzed by KCN/18-crown-6247 or n-BujSnCN, gives the corresponding cyanohydrin trimethylsilyl ethers in high yields. 

Cyanosilylation. Me3SiCl mediates formation of a-cyanohydrin trimethylsilyl ether using NaCN in DMSO. This combination is more economical than MesSiCN. ... 

Johnson s group developed a catalytic asymmetric cyanation/1,2-Brook rearrangement/C-acylation of acylsilanes with cyanoformates (Scheme 19.14). In the presence of (i ,/ )-(salen)Al 19, the corresponding cyanohydrin trimethylsilyl ethers of a-keto esters were obtained in moderate to good enantioselectivities (61-82% enantiomeric excess). Access to chiral (silyloxy)nitrile anions is facilitated by metal cyanide-promoted Brook rearrangement reaction of acylsilanes. 

In 2001, North et al. reported the development of bimetallic Ti(IV) and V(IV) salen complexes (100) and (102) as the optimal catalysts for the asymmetric addition of trimethylsilyl cyanide to ketones and aldehydes (Scheme 16.28) [32]. Both catalysts predominantly gave the (S)-enantiomer of the cyanohydrin derivative. Complex (100) proved to be optimal for quantitative conversion of both electron rich and electron deficient ketones into the corresponding cyanohydrin trimethylsilyl ethers... 

Aldehydes and ketones are readily transformed into the corresponding cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of Lewis acids (eq 1), triethylamine, or solid bases such as Cap2 or hydroxyapatite. The products can be readily hydrolyzed to the corresponding cyanohydrins. The cyanosilylation of aromatic aldehydes can be achieved with high enantioselectivity in the presence of catalytic amounts of a modified Sharpless catalyst consisting of titanium tetraisopropoxide and L-(+)-diisopropyl tartrate (eq 2). Catalysis with chiral titanium reagents yields aliphatic and aromatic cyanohydrins in high chemical and optical yields... 

Addition to Carbonyls, Imines (Strecker-type Reactions), and Heteroaromatic Rings (Reissert-type Reactions). Cyanohydrin trimethylsilyl ethers are of significant synthetic interest as they can be transformed into a variety of multifunctional intermediates. Aldehydes and ketones can be enantioselectively converted to cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of a Lewis acid and a chiral ligand. Enantioselective and/or diastereoselective formation of cyanohydrins and their derivatives has been reported and most of these reactions involve chiral ligands and metal catalysts containing Ti (eq 24), Sm (eq 25), and A1 (eq 26). ... 

The protection of carbonyl functions by reaction with trimethylsilyl cyanide to form the cyanohydrin trimethylsilyl ethers is subject to catalysis by potassium cyanide in the presence of 18-crown-6, tetrabutylammonium cyanide or resin bound tetraalkyl-ammonium cyanide [27, 29]. The nucleophilic cyanide ion is believed to attack the carbonyl yielding a cyanohydrin anion. This anion is silylated by trimethylsilyl cyanide with generation of an equivalent of cyanide anion. The sequence is shown in equation 7.13. Accordingly, 3-pentanone and 4- -butylcyclohexanone are cyanosil-... 

The catalyst (10c) turned out to be effective for highly enantioselective hydrocya-nation of a wide range of ketones to give cyanohydrin trimethylsilyl ether with high ees (Scheme 2.44) [97]. 

In the case of TMEDA, stereoselection in favor of the syn product (98 2) is enhanced over that achieved with Diiso-propylethylamine (94 6). Along with bases sueh as Triethy-lamine and ethylisopropylamine, TMEDA facilitates the preparation of cyanohydrin trimethylsilyl ethers from aldehydes and Cyanotrimethylsilane. It has been suggested that eoordination by nitrogen induces formation of an active hypervalent cyana-tion intermediate from cyanotrimethylsilane. The conjugate addition of thiols to enones has been successfully catalyzed by using TMEDA in methanol at room temperature, as exemplified by the reaction of 10-mercaptoisobomeol and 4-/-butoxycyclopentenone... 

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