Trimethylsilyl cyanide nitrile synthesis

Allylalion of the alkoxymalonitrile 231 followed by hydrolysis affords acyl cyanide, which is converted into the amide 232. Hence the reagent 231 can be used as an acyl anion equivalent[144]. Methoxy(phenylthio)acetonitrile is allylated with allylic carbonates or vinyloxiranes. After allylation. they are converted into esters or lactones. The intramolecular version using 233 has been applied to the synthesis of the macrolide 234[37]. The /i,7-unsaturated nitrile 235 is prepared by the reaction of allylic carbonate with trimethylsilyl cyanide[145]. 

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. 

The asymmetric Strecker synthesis of a-amino nitriles from Schiff bases of a-methylbenzyl-aminc is improved by the use of trimethylsilyl cyanide, instead of hydrogen cyanide and by promotion of the transformation with a Lewis acid, preferably zinc chloride43. Thus, from the butyraldimine 2, the amino nitrile is synthesized with a yield of 98.5% and an ee of 68.5%. 

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

The addition of hydrogen cyanide to a carbonyl group results in the formation of an a-hydroxy nitrile, a so-called cyanohydrin (A, Scheme 6.1) [1]. Compounds of this type have in many instances served as intermediates in the synthesis of, e.g., a-hydroxy acids B, a-hydroxy aldehydes C, fS-amino alcohols D, or a-hydroxy ketones E (Scheme 6.1) [1], In all these secondary transformations of the cyanohydrins A, the stereocenter originally introduced by HCN addition is preserved. Consequently, the catalytic asymmetric addition of HCN to aldehydes and ketones is a synthetically very valuable transformation. Besides addition of HCN, this chapter also covers the addition of trimethylsilyl cyanide and cyanoformate to car-... 

In addition to its use in the preparation of nitriles, trimethylsilyl cyanide (TMS-CN) is also becoming a very useful reagent for the preparation of isocyanides. 1-Chloroadamantane, for instance, gives rise to 78% of the corresponding isonitrile in the presence of catalytic amounts of TiCU (Scheme 26). Of special interest is the remarkably regioselective and stereoselective synthesis of trimethylsilyloxyalkyl isocyanides (Scheme 26) from oxiranes and TMS-CN in the presence of, for example, zinc halides (see also Section 1.8.1.3). < ... 

Multicomponent reactions (MCRs) were applied to the synthesis of substituted isoxazolines. For example, 64 was obtained by addition of nitro-alkene 60 and acrylate 61 to a solution of isonitrile 59 generated in situ by reaction of trimethylsilyl cyanide and isobutene oxide in the presence of Pd(CN)2 <05OL3179>. This cascade MCR is believed to occur through [1+4] cycloaddition of 59 with 60, subsequent fragmentation of 62 and 1,3-DC of nitrile oxide 63 with 61. Under microwave irradiation, reaction times could be reduced from several hours to 15 min, with comparable yields. 

Due to the high price of trimethylsilyl cyanide, access to alternative cyanation reagents is desirable. In this regard, cyanoformate esters (CNCO2R) have been employed, providing direct access to O-alkojycarbonyl-functionalised cyanohydrins, which are stable and not easily hydrolysed by moisture in air. Moreover, they are useful synthetic intermediates and can be applied in the synthesis of a-amino alcohols and (3-substituted unsaturated nitriles from O-carbonylated allylic cyanohydrins. ... 

Fossey and Richards have already reported the synthesis of Pt and Pd bisoxazo-line containing NCN-pincer complexes these complexes were found to be active as catalysts for the Michael reaction of activated nitriles and the aldol reaction between isonitriles and aldehydes [43]. Recently, they continuously studied on the addition of trimethylsilyl cyanide to benzaldehyde (la) catalyzed by complexes (139) (Scheme 16.37) [44]. The most effective catalyst was found when trifluo-romethanesulfonate (OTf) was used as counteranion, resulting in good conversion of benzaldehyde under the standard conditions used. Furthermore, in the addition of trimethylsilylcyanide (TMSCN) to N-benzylideneaniline (110a) in the presence of (130) (1 mol%) provided (141) in a 77% conversion. 

The preferred catalysts for the one-step co-cyclization of acetylene and acetonitrile (or alkyl cyanides in general) to give a-picoline (or 2-alkylpyridines) are i/ -Cp-cobalt cod or / -trimethylsilyl-Cp-cobalt cod (eq. (2)). The a-picoline synthesis is best performed in pure nitrile without any additional solvent [5 d]. 

Trimethylsilyl [ C]cyanide is conveniently accessible from trimethylsilyl chloride, Na CN and Nal in the presence of lutidine or pyridine ". In carbon-14 synthesis it is normally generated in situ and used immediately in subsequent Lewis acid catalyzed chemical transformations. It is useful for some reactions in which alkah metal [ " C]cyanides normally fail, such as cyanide addition to acetals and aromatic and heteroaromatic aldehydes and ketones. Examples include the Znl2-catalyzed addition of TMS " CN to 2-furaldehyde followed by hydride reduction of the resultant silylated cyanohydrin to the aminoalcohol 96 " and the SnCLj-catalyzed formation of D-[l- " C]allonitrile 98, obtained from reaction of TMS " CN to the 0-acetylated hemiacetal 97 (Figure 7.26). Subsequent addition of H2Se to the nitrile group, cyclocondensation of the intermediate selenoamide in situ with ethyl bromopymvate and deprotection yielded 99, precursor to [2- " C]CI-935, a compound with... 

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