Allyl cyanide synthesis

The only practical methods for the preparation of vinylacet.ic acid involve hydrolysis of allyl cyanide 6 carbonation of allylmag-nesium bromide 8 or the malonic acid synthesis.9... 

The hydroformylation of unsaturated nitriles such as crotonitrile and allyl cyanide is a potential route towards chiral amino alcohols, which are building blocks in the synthesis of pharmaceuticals. The hydroformylation of acrylonitrile was studied in the early years [5], but lately the hydroformylation of allyl cyanide and crotonitrile have also been investigated [25,81]. 

The asymmetric hydroformylation of allyl cyanide has recently focused the interest of researchers because the iso-aldehyde derivative can be easily transformed into 2-methyl-4-aminobutanol, a useful building block, for instance for the asymmetric synthesis of tachikinin (58), a novel NK1 receptor agonist developed by Takeda [82], It should be noticed that this aldehyde is not accessible via the hydroformylation of crotononitrile. 

The formation of olefinic nitriles from allylic halides is best accomplished with dry, powdered cuprous cyanide rather than with alcoholic alkali cyanides, with which side reactions such as isomerization and alcoholysis of the double bond are particularly bothersome. With cuprous cyanide the yields in the synthesis of allyl cyanide and methal-lyl cyanide are 84% and 86%, respectively. Higher allylic halides are subject to allylic rearrangements thus cuprous cyanide acts on crotyl halide (CH,CH CHCHjX) and methylvinylcarbinyl halide (CH,CHXCH = CH,) to produce the same mixture of isomeric nitriles (9 1) regardless of which halide is treated. Numerous cyanides of the allylic type (Cj-Ci4) have been prepared, although the possibility of an isomerization has not been considered. A similar isomerization has been observed in the reaction of sorbyl chloride and potassium cyanide. ... 

J,V-Unsaturated carboxylic acids and their derivatives are valuable synthetic intermediates for various natural products. Two typical multi-step processes for the synthesis of p.y-unsaturated acids, Knoevenagel reaction/isomerization with base and allylic cyanide/hydrolysis,3 are those most commonly used. Other new methods have been developed 4-7 however, there is a problem with E/Z stereoselectivity. One straightforward way to obtain p,y-unsaturated acids is by the carboxylation of an allyl metal Intermediate. In the substituted allylic series, the reaction usually occurs at the more sterically hindered terminus. A stereospecific route for the synthesis of homogeranlo acid and homoneric acid by carboxylation of the lithiated allylic sulfone... 

Pro-azaphosphatranes lb or Id catalyze the reaction of activated allylic compounds with aromatic aldehydes to produce either a Baylis-Hillman product or a j8,y-unsaturated 1,2-addition product, depending on the type of allylic compound employed [131]. As seen in Eqs. (18) and (19), the activated allylic compounds shown react efficiently with aromatic aldehydes in the presence of 20 to 40 mole percent of lb or Id to give exclusively a-addition products. Such products are useful intermediates for the synthesis of substituted tetrahydrofurans through base-promoted electrophilic cyclizations. To our knowledge there have been only a few reports in which allylic cyanides and esters of the type used here have been utilized in 1,2-addition to aldehydes [131]. In those reports, an ionic base was used, y addition was observed, or a mixture of a- and y-addition products were obtained. The latter two observations contrast ours in which exclusive a-addition occurred. 

As vinylarene substrates do not provide an entry to conunercially interesting products, many research groups have been investigating asynunetric hydroformylation of more useful olefins. Independently, workers from DSM and from Dow investigated the asynunetric hydroformylation of allyl cyanide, which provides access to (R)-4-amino-2-methylbutanol, an intermediate in the synthesis of TAK-637, a drug in development... 

Cobley CJ, Gardner K, Klosin J, Praquin C, HiU C, Whiteker GT, Zanotti-Gerosa A, Petersen JL, Abboud KA. Synthesis and application of a new bisphosphite ligand collection for asymmetric hydroformylation of allyl cyanide. J. Org. Chem. 2004 69 4031 040. 

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. 

An efficient primary amine synthesis via iV-diisobutylaluminium imines has been described. A cyanide R CN (R1 = Bu, CsHn, Ph, 2-furyl or 2-thienyl) is treated with diisobutylaluminium hydride and the product is converted into the amine by reaction with an organomagnesium or organolithium compound R2M (R2 = Bu, t-Bu, allyl or benzyl)... 

Imidates, rearrangement of, 14, 1 Imines, additions of allyl, allenyl, propargyl stannanes, 64, 1 additions of cyanide, 70, 1 as dienophiles, 65, 2 synthesis, 70, 1 Iminium ions, 39, 2 65, 2 Imino Diels-Alder reactions, 65, 2 Indoles, by Nenitzescu reaction, 20, 3 by reaction with TosMIC, 57, 3 Ionic hydrogenation, 71, 1 Isocyanides, in the Passerini reaction, 65, 1... 

Fig. 30 Synthesis of 2,3-unsaturated allyl glycosides or glycosyl cyanides...

A synthesis of 5-coniceine by a transannular reaction has been reported (81TL2075). Treatment of N-allyl-N-3-butenyl-N-benzyloxycarbonylamine with thexylborane followed by cyanidation afforded an azacyclanone in 35% yield which could be transformed into 5-coniceine by catalytic reduction (Scheme 28). 

Me3SiCN is a convenient, reactive cyanide donor in transition metal-catalyzed processes. The Pd-catalyzed reaction of aryl iodides with Me3SiCN is useful for the synthesis of aryl cyanides.257 Me3SiCN works also as an effective co-catalyst for the Pd-catalyzed cyanation of aryl iodides with KCN.258 Allylic acetates, carbonates, and the related compounds undergo the Pd-catalyzed cyanation with Me3SiCN.259-261 The tandem cyclization-cyanation reaction of 2-bromo-l,6-heptadienes with Me3SiCN proceeds under catalysis by an Ni complex (Equation (68)).262... 

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