Synthesis acyl cyanides

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]. 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

To form the stereocenter at C-3 a direct reduction-alkynylation sequence was applied, that provided the diastereomeric homopropargylic alcohols 83 in a ratio of syn anti=76l2A, The major isomer syn-S3 was isolated in 55% yield. The key step of the synthesis was an intramolecular imidotitanium-al-kyne [2+2] cycloaddition/acyl cyanide condensation. With this sequence the pyrrolidine ring was formed and all the carbon atoms of the alkyl side chain were established in acrylonitrile 84. The reduction of the imine double bond proceeded stereoselectively and the nitrile group was removed reductively en route to the target compound. 

Borch, R. F. Levitan, S. R. Van-Catledge, F. A. The reaction of acyl cyanides with Grignard reagents. J. Org. Chem. 1972, 37, 726—729. Gallina, C. Giordano, C. Selected methods for the oxidation of l,l,l-trichloro-2-alkanols. An efficient modification using chromic acid. Synthesis 1989, 466-468. 

The facial diastereoselectivity derived from-the ratio (3 + 4)/(5 + 6) was 50%, while the exo/endo selectivity derived from the product ratio (3 + 5)/(4 4- 6) was 40%. Oxetanes 9a,b were obtained with a low diastereoselectivity from the reaction of (R)-isopropylideneglyceraldehyde 7 with 3,4-dimethylfuran 8 [6]. Oxetanes 9a,b have been used for the synthesis of asteltoxin. Enantiopure acyl cyanides were used in the same way as chiral carbonyl reaction partners [7] and camphor for the addition with electron-poor alkenes like dicyanoethylene [8]. In the latter case the reaction occurs in the S i state of the carbonyl compound. 

Asymmetric synthesis by means of a cyandiydrin is an imprvtant process in organic synthesis, because the cyanohydrin can be easily converted into a variety of valuable synthetic intermediates, such as a-hy-droxy ketones, a-hydroxy acids, y-diketones, p-amino alcohols, 4-oxocarboxylic esters, 4 xonitriles, a-amino acids and acyl cyanides. More specifically, the (S)-cyanohydrin of m-phenoxybenzaldehyde is a building block for the synthesis of the insecticide deltamethrin, or (IR)-cis-pyrethroids. ... 

Oxidation of a cyanohydrin derived from a conjugated aldehyde (as the 0-TMS derivative) using py-ridinium dichromate (PE)C) in DMF gave an a,3-unsaturated lactone (5 -butenolide) as the major product (equation 12). Simple nonconjugated cyanohydrins are not satisfactory substrates for the synthesis of acyl cyanides using PDC, because they seem to add to the initially formed acyl cyanides, leading ultimately to cyanohydrin esters. Oxidation of cyanohydrin to acyl cyanides can be carried out either by means of manganese dioxide, ruthenium-catdyzed oxidation with t-butyl hydroperoxide or NBS. ... 

Sometimes a Lewis acid such as zinc iodide is added in catalytic amounts. Side reactions may sometimes occur if acyl cyanides carry hydrogen atoms in the a-position and are, therefore, enolizable. In those examples trimethylsilyl chloride, which is formed during the reaction, may react to give trimethyl-silylated enol ethers (8). This methodology can be applied successfully to the synthesis of such com-... 

Table 13 Synthesis of Aliphatic, a. -Unsaturated and Benzylic Acyl Cyanides...

Nagra, B.S., Shaw, G., and Robinson, D.H., A novel synthesis of acyl cyanides from diethyl phosphorocyanidate and some 1-substituted imidazole carboxylic acids including a D-ribofuranoside, J. Chem. Soc., Chem. Commun., 459, 1985. 

Reaction of acyl cyanides with amidrazones or guanidin-2-amine has been used for the synthesis of l,2,4-triazin-5-amines 11,172 or l,2,4-triazine-3,5-diamines 12. The reaction proceeds via 4-amino-2,3-diazabutadiene-l-carbonitriles.333- 336... 

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