With cyanotrimethylsilane

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction. For aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-54) competes. With oc,p-unsaturated aldehydes and ketones, 1,4 addition competes (15-33). Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MesSiCN) in the presence of a Lewis acid or base, followed by hydrolysis of the resulting O-trimethylsilyl cyanohydrin (52). The use of chiral additives in this latter reaction leads to cyanohydrins with good asymmetric... 

Firstly, we examined the asymmetric hydrocyanation of 3-phenylpropanal. When 3-phenylpropanal was treated with cyanotrimethylsilane using the chiral titanium alkoxide prepared from dichlorodiisopropoxytitanium and the chiral 1,4-diol 17b in toluene at room temperature, only a trace amount of the... 

Table 8. Asymmetric Hydrocyanation of Aldehydes with Cyanotrimethylsilane...

The optical purity of these cyanohydrins was influenced largely by the reaction temperature and was very low at room temperature. Furthermore, when benzaldehyde was treated with cyanotrimethylsilane in the presence of the chiral titanium reagent and MS 4A at room temperature, followed by stirring the reaction mixture at -65 °C for 1 day, the optical purity of mandelonitrile 23b was ca. 10%. These results indicated that the cyanohydrins were produced as kinetic products in this catalytic process. 

J. D. Elliott, V. M. F. Choi, and W. S. Johnson, Asymmetric synthesis via acetal templates. 5. Reactions with cyanotrimethylsilane. Enantioselective preparation of cyanohydrins and derivatives, J. Org. Chem. 78 2294 (1983). 

Alkoxy or 2,2-dialkoxy nitriles.10 Ketals or orthoesters are converted into 2-alkoxy or 2,2-dialkoxy nitriles, respectively, by reaction with cyanotrimethylsilane in the presence of SnCl2 or BF3-0(C2H5)2 as catalyst. A typical reaction is the preparation of dimethoxyacetonitrile (1), which is a useful reagent for conversion of alkyl halides to the homologous methyl carboxylate (equation I). 

Reissert compounds.M Pyridine does not form a Reissert compound, but pyridazine and pyrimidine react with cyanotrimethylsilane and benzoyl chloride to form a monocyclic Reissert compound.12 Example ... 

Asymmetric hydrocyanation of aldehydes.3 This reaction can be effected by reaction of aliphatic or aromatic aldehydes with cyanotrimethylsilane and an optically active reagent (1) derived from (2R,3R)-tartaric acid, and dichlorodiisopro-poxytitanium(IV). The actual chiral reagent may be 2, shown by H NMR to be... 

Dialkyl-l-naphtholsS The p-quinols 1, formed by addition of R Li to the monoadduct of 1,4-naphthoquinone with cyanotrimethylsilane (5, 722), can undergo a second addition of R Li or R2Li to provide the diol 2. Reduction of 2 with HI... 

A simple one-pot procedure for the transformation of tertiary alkyl chlorides into the corresponding nitriles has been developed. This reaction involves the treatment of the alkyl chloride with cyanotrimethylsilane in the presence of tin(IV) chloride and occurs in good yields at room temperature (equation 40). This procedure has also been successful in the preparation of bridgehead nitriles356. 

The Lewis acid-catalyzed reaction of epoxides with cyanotrimethylsilane (Me3SiCN) forms /3-siloxy nitriles.252 Highly enantioselective desymmetrization of / >-epoxides with Me3SiCN can be achieved by chiral Ti and Yb catalysts (Equation (67)).255 256... 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

The first study of catalysis by a nanoporous coordination polymer used a simple lamellar coordination polymer of Cd and 4,4 -bipyridine in which several aldehydes were tested for cyanosilation with cyanotrimethylsilane.86 Good yields were found for smaller molecules, with progressively poorer yields for larger ones, while control experiments using Cd(N03)2 and 4,4 -bipyridine as catalysts resulted in no reaction, confirming the role of the coordination polymer s porosity in catalyzing the reaction. 

Some of the starting compounds were commercially available only as acids or anhydride. The respective acyl chlorides were obtained according to the thionyl chloride method of Smith et al. (1991). Reactions with cyanotrimethylsilane were completed under water-free conditions and in an argon atmosphere (Hiinig and Schaller, 1982). Glassware was dried in an oven directly before use. 

Cleavage of epoxides (11,147). Cleavage of the epoxide (1), or the acetate or the trimethylsilyl ether of (R)-cyclohexenol with cyanotrimethylsilane (excess) catalyzed by zinc iodide proceeds regio- and stereoselectively to give 2 in 71% yield. This product can be converted into the aminodiol 3 with three contiguous chiral centers. ... 

The deoxycyanation of 2-substituted quinoxaline 4-oxides 22 with cyanotrimethylsilane in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene gives the corresponding 3-substituted quinoxa-line-2-carbonitriles 23.- ... 

Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN) (see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MeaSiCN) " in the presence of a Lewis acid or base, " ... 

Reaction of cyclopropenones with cyanotrimethylsilane was effectively catalyzed by triphenylphosphane to give furancarbonitriles 5. ... 

The nitro group in allylic nitro compounds (86) is replaced by the cyano group upon treatment with cyanotrimethylsilane (Scheme 140), although the regioselectivity is low. ... 

A-chlorosuccinimide provides (3 S, 4 S)-3,4-bis(TBSO)-l-chloropyrrolidine (771). Dehydrochlorination with DBU in benzene affords a cyclic imine that reacts with cyanotrimethylsilane in the presence of catalytic zinc iodide to afford an epimeric mixture of aminonitriles. Acidic hydrolysis of the nitrile, esterification of the resulting acid, Cbz-protection of the basic amine, and chromatographic separation affords 772 in 28% yield and 774 in 42% yield. These are converted respectively to either (25, 35,45)-3,4-dihydroxyproline (773) or (2R,3>S,4S)-3,4-dihydroxyproline (775) [230] (Scheme 169). 

Stereoselective reactions with acetals. Noyori et al. (10,438) have used this Lewis acid to promote an aldol-type reaction between enol silyl ethers and acetals and have noted high. syn-selectivity in this process. Molander and Haar report that reaction of acetals with cyanotrimethylsilane promoted by TMSOTf results in a-alkoxy cyanides and that this reaction can be diastereoselective when the acetal is substituted at the 4-position by an alkoxy group. The diastereoselectivity depends on the nature of the acetal and the 4-alkoxy group. Dimethoxy acetals show slight diastereoselectivity, but diisopropoxy and dibenzyl acetals can show diastereoselectivity of 5-10 1. The diastereoselectivity also depends on the type of 4-substituent. Acetoxy and t-butyldimethylsilyloxy groups have no effect on the diastereoselectivity, but methoxy, benzyloxy, and allyloxy groups promote anri-selectivity. Since a metal template is not involved, the diastereoselectivity... 

Two structural types of cyanoiodonium salts are known (dicyano)iodonium triflate, (NC)2lOTf [399,400] and aryl(cyano)iodonium derivatives, Arl(CN)X [ 146,460,508,509]. (Dicyano)iodonium uiflate 277 can be prepared by the reaction of iodosyl triflate (375) (Section 2.1.1.2) with cyanotrimethylsilane in dichloromethane (Scheme 2.105). In the solid state, compound 277 is thermally unstable and air-sensitive it completely decomposes at room temperature in 2-5 min forming cyanogen iodine, ICN and explodes when exposed to air. However, it can be stored at -20 °C under nitrogen for several days [400]. Despite its low stability, cyanide 277 can be used in situ for the very mild and efficient preparation of various bis(heteroaryl)iodonium salts by an iodonium transfer reaction with the respective stannylated heteroarenes (Section 2.1.9.1.1). 

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... 

Good yields of 3-(trimethylsiloxy)nitriles are also obtained from the reactions of oxiranes with cyanotrimethylsilane in the presence of lanthanide salts, or when the reaction is catalyzed by AICI3 or diethylaluminum chloride (eq 11). Ring opening of chiral glycidyl derivatives by MesSiCN catalyzed by Ti(0-i-Pr)4 or Al(0-i-Pr)3 occurs in a regiospeciflc and highly stereoselective manner (eq 12). ... 

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). ... 

Preparative Methods dicyanodimethylsilane is conveniently prepared by the reaction of dibromodimethylsilane. or dichlorodimethylsilane with silver(I) cyanide lithium cyanide/ sodium cyanide/ and potassium cyanide can also be used in place of silver cyanide. A method which uses hydrogen cyanide as a source of cyano groups and a procedure which utilizes transcyanation with cyanotrimethylsilane have also been reported. Dicyanodimethylsilane is obtained as colorless crystals via these methods. 

Trifluoromethyl isocyanate undergoes an insertion reaction with cyanotrimethylsilane at room temperature to give the insertion product 303 in 70 % yield... 

Two equivalents of the isocyanate react with cyanotrimethylsilane at 50 °C to give a flve-membered ring [2+2+1] cycloadduct. Af,Af -disubstituted 5-trimethyl-silyliminoimidazolidinediones are obtained in the reaction of aryl- or arenesulfonyl isocyanates with trimethylsilyl cyanide. In the reaction with arenesulfonyl isocyanates the initially formed insertion products can also be isolated. The reaction of trimethylsilylamldes with phenylcarbonyl isocyanate also affords the insertion product. 

Cyanobenziodoxoles 113—115 were originally synthesized in one step by treatment of hydroxybenziodoxoles 101 with cyanotrimethylsilane (Scheme 17 1996MC50, 1995TL7975), or from acetoxybenziodoxole andcyanotri-m ethylsilane (1996H47). 

More recently modified procedures involve the reactions of chlorobenziodoxole 116 or acetoxybenziodoxole 117 with cyanotrimethylsilane in the presence of fluoride anion (Scheme 18 2015OBC365). 

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