Additions cyanotrimethylsilane

Conj ugate Additions. Cyanotrimethylsilane reacts with a,p-unsaturated ketones in the presence of Lewis acids (aluminum chloride, tin(II) chloride, triethylaluminum) to yield, upon hydrolysis, the corresponding 1,4-addition products (eqs 5 and 6). This methodology is superior to other procedures. By controlling the reaction conditions and the stoichiometry of the reaction, the kineticaUy controlled 1,2-addition products can also be obtained in bigb yields (eq 7). ... 

The cyanohydrin-forming addition of cyanide or cyanide equivalents (e.g.. cyanotrimethylsilane) to optically active a-amino aldehydes occurs diastereoselectively. 

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... 

Conjugate addition. In the presence of 1 equivalent of triethylaluminum, cyanotrimethylsilane undergoes conjugate addition to a,/ -enones in high yield. The products arc converted into /J-cyano ketones by acid hydrolysis. The addition is kinetically controlled in toluene at room temperature, but thermodynamically controlled in refluxing THF (equation I). 

Addition of CN Cyanotrimethylsilane, 87 Sodium cyanide, 185 Addition a to carbonyl groups Chloromethyldiphenylsilane, 74... 

Asymmetric Strecker amino acid synthesis Addition of cyanotrimethylsilane catalyzed by ZnCl2 to optically active aldimines formed from 2,3,4,6-tetrapivaloyl-3-D-galactopyranosylamine as the chiral auxiliary can result in either (R)- or (S)-a-aminonitriles, depending on the solvent. THF or isopropanol favors (R)-dia-stereomers, whereas CHC13 favors the (S)-diastereomers. 

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... 

HFA and cyanotrimethylsilane react stoichiometrically with formation of the substituted cyanhydrin 9 (775). Increasing the molar ratio of the reactants to 4 1 yields, in addition to 9, compound 10, with nitrile-isonitrile equilibrium competing with direct attack of HFA (242). The five-membered ring is also formed in the reaction of organic iso-nitriles with HFA (188). The same structural feature in addition to insertion has been found when triethylamine is present as a catalyst, as well as minor amounts of 9 (83, 242). 

Addition to ketones. Potassium cyanide in combination with 18-crown-6 is generally superior to Znij as the catalyst for additii n of cyanotrimethylsilane to ketones substituted at the a-position with an electron-withdrawing group. 

Cyanosilylation. The chiral titanium reagent, prepared from the lithium salt of BINOL with TiCL, has been used as a catalyst for the asymmetric addition of cyanotrimethylsilane to aldehydes. In the example shown, the cyanohydrin is obtained with <82% ee (eq 9). 

Cyanosilylation. Another preparative procedure of BINOL-TiCl2 and the use thereof was reported in the asymmetric catalysis of the addition reaction of cyanotrimethylsilane to aldehydes. The dilithium salt of BINOL in ether was treated with... 

Enantioselective Cyanohydrin Formation. Magnesium complexes formed with the anionic semicorrin-type ligand (5) catalyze the addition of Cyanotrimethylsilane to aldehydes, leading to optically active trimethylsilyl-protected cyanohydrins. In the presence of 20 mol % of the chloromagnesium complex (9), prepared from equimolar amounts of (5) and BuMgCl, cyclohexanecarbaldehyde is smoothly converted to the corresponding cyanohydrin derivative with 65% ee. Addition of 12 mol % of the bisoxazoline (10) results in a dramatic increase of enantioselectivity to 94% ee (eq 8). Replacement of (10) by its enantiomer reduces the selectivity to 38% ee. This remarkable... 

In the addition reaction of cyanotrimethylsilane [147] to aliphatic aldehydes, another synthetic application of a BINOL-Ti catalyst was reported by Reetz [88]. In this instance, however, BINOL-TiCh was prepared by treatment of the lithium salt of BINOL with TiCU in ether (vide supra). The BINOL-TiCh thus obtained was used as a catalyst for the cyanosilylation reaction to give the cyanohydrins in up to 82 % ee (Sch. 62). 

Using nickel(O), generated from nickel(II) chloride with diisobutylaluminum hydride, as catalyst, cyanotrimethylsilane underwent addition to l-methylene-2-phenylcyclopropanes to give 2-phenyl-l-(trimethylsilylmethyl)cyclopropane-l-carbonitriIes 1 in poor yield. Palladium catalysis led to opening of the cyclopropane ring as the major process. 

Cyanotrimethylsilane is also a convenient source for cyanation of cyclopropanones, as exemplified by its addition to 2-(trimethylsilyl)cyclopropanone (5) in the presence of catalytic amounts of potassium cyanide and 18-crown-6. ... 

Products 283 of cw-addition are obtained regio-and stereospecifically from terminal acetylenes 282 (R = Ph or substituted Ph) and cyanotrimethylsilane in the presence of a... 

Scheme 7.19 Enantioselective addition of cyanotrimethylsilane to imines using 27 and 28.

Reactions with Oxiranes, Oxetanes, and Aziridines. Lewis acids, lanthanide salts, and titanium tetraisopropoxide or aluminum isopropoxide catalyze the reactions of cyanotri-methylsilane with oxiranes, oxetanes, and aziridines, yielding ring-opened products. The nature of the products and the regio-selectivity of the reaction are primarily dependent on the nature of the Lewis acid, the substitution pattern in the substrate, and the reaction conditions. Monosubstituted oxiranes undergo regiospe-cific cleavage to form 3-(trimethylsiloxy)nitriles when refluxed with a slight excess of cyanotrimethylsilane in the presence of a catalytic amount of potassium cyanide-18-crown-6 complex (eqs 8-10). The addition of cyanide occurs exclusively at the least-substituted carbon. 

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). ... 

Excellent enantioselectivity has also been achieved in the reaction between imines and cyanotrimethylsilane, which provides an effective synthesis of chiral a-amino acids. Ti-catalyzed reactions using a chiral tripeptide Schiff base have been developed to realize such transformations (eq 30). In addition, a combination of 2,2 -biphenol and Cinchonine as chiral ligands has been employed to effect such reactions (eq 31). An enantioselective route was also developed for the conversion of readily prepared... 

Conjugate Addition. Catalytic enantioselective conjugate addition of cyanotrimethylsilane to a,/3-unsaturated imides has been reported to afford 1,4-addition products in excellent yield and enantiomeric excess (eq 35). Under the catalysis of a chiral gadolinium complex, cyanotrimethylsilane can undergo facile conjugate addition to enones (eq 36) and a, 6-unsaturated... 

A-acylpyrroles (eq 37) with high enantioselectivity. The conjugate addition of cyanotrimethylsilane to, -disubstituted a,/3-unsaturated carbonyl compounds catalyzed by a chiral Sr complex provides a convenient route for the asymmetric construction of a quaternary carbon (eq 38). ... 

Cyanotrimethylsilane has found extensive use as a reagent for a variety of synthetic transformations, and an improved synthesis has been described. The preparation of silylated cyanhydrins has also been improved in a two-stage one-pot synthesis which utilises cyanotrimethylsilane, prepared without isolation and prior to the addition of the carbonyl component (Scheme 24). ... 

---