Allylation of acyl cyanide

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. 

Indium-mediated coupling of allylic bromides with acyUmidazoles or -pyra-zoles in aqueous media gives the corresponding ketones (Scheme 8.46) [68]. Indium-mediated allylation of acyl cyanides with allyl halides in aqueous media affords a variety of /fy-urisaturalcd ketones (Scheme 8.47) [69]. Indium is effective in 2-pyridyl esters with allyl bromides or with iodide in pure water (Scheme 8.48) [70]. 

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]. 

Typically, oc,0-unsaturated esters, a,0-unsaturated aldehydes and a,0-unsaturated nitriles are poor acceptors for the Lewis acid catalyzed silylallylation procedure, but they are excellent acceptors for the complementary fluoride ion mediated allylation procedure (cf. Volume 4, Chapter 1.2, Section 1.2.2.1.7). Other suitable acceptors include 1,4-quinones,70 a,0-unsaturated acyl cyanides (162),718 silyl ot,0-enoates (163)71b and nitroalkenes (Scheme 26) 72 reduction (titanium(III) trichloride) of the intermediate nitronates arising from nitroalkene allylation affords y,8-enones (166). 

Conjugated—a,/)-unsaturated or aromatic—aldehydes are oxidized by manganese dioxide in the presence of one equivalent of sodium cyanide to give an acyl cyanide (Formula C in Figure 17.18) via an intermediate cyanohydrin (B in Figure 17.18), which is also either an allylic or a benzylic alcohol. Alcohols of this kind can be oxidized by a relatively weak oxi-... 

Acid-catalyzed addition of aliphatic, aromatic or heteroaromatic cyanohydrins to ethyl vinyl ether, n-butyl vinyl ether or dihydro-4//-pyran provides base stable, protected cyanohydrin derivatives. Phase transfer catalyzed alkylation of aliphatic cyanohydrins with allylic bromides gave a-substituted a-allyl-oxyacetonitrile. Carbonyl compounds react wiA cyanide under phase transfer catalysis to give cyanohydrin anions, which are trapped by an acyl chloride or ethyl chloroformate to give acyl- or alkoxycarbonyl-protected cyanohydrins respectively. The reduction of the carbonyl group of an acyl cyanide by NaBH4 under phase transfer conditions followed by esterification serves as an alternative route to aldehyde-derived cyanohydrin esters. ... 

Corey et al.a were interested in developing a simple procedure for oxidation of allylic alcohols to carboxylic acids without cis-irans isomerization of the ,/3-unsaturated linkage. They reasoned that in the presence of hydrogen cyanide and cyanide ion the a,/3-unsaturated aldehyde would be converted into the cyanohydrin which would be oxidized by Mn02 to an acyl cyanide, which in the presence of an alcohol would be converted into an ester ... 

Acylcyanides. The oxidation of cyan cyanides is catalyzed by (PPhsljRuCI.-. Th acylation of amino alcohols and polyaminci Carbonylation. A new route to 2i5//> lation of allylic alcohols. ... 

Conversion of Allylic Alcohols to a, -Ethylenic Esters and Amides. This procedure was first described by Corey. The key step is the sequential formation and oxidation of a cyanohydrin. In the presence of an alcohol or an amine the resulting acyl cyanide leads by alcoholysis or aminolysis to the corresponding Q ,/3-ethylenic ester or amide (eqs 13-15). 

It should be pointed out that manganese dioxide is a mild oxidant that usually converts primary allylic alcohols into conjugated aldehydes without significant further oxidation to carboxylic acids." However, in the presence of HCN and cyanide, the a, -unsaturated aldehydes could be converted into cyanohydrins, which are susceptible to the oxidation of Mn02 to acyl cyanides. In the presence of an alcohol, the a,j8-unsaturated esters are obtained. It should be emphasized that this reaction works only for a,j8-unsaturated aldehydes and will not cause any cis-trans isomerization for the a,/3-unsaturated double bond. For example, benzaldehyde (> 95%), cinnamaldehyde (> 95%), furfural (> 95%), geranial (85-95%), and farnesal (> 95%) have all been transformed into the corresponding methyl esters. ... 

Cyanide addition to the lactamic carbonyl group has been described in a reaction in which the cyanide ion acts as a catalyst (Fig. 14).The intermediate acyl cyanide can be attacked by an added nucleophile (allylic, propargylic, benzylic alcohols, aniline, benzylmercaptan). Comparative experiments were carried out using more classical procedures, such as under catalysis by potassium cyanide with stirring at room temperature, and with sodium alkoxides at -78 C. This last method provides the highest yields, up to 95% in most of the cases tested, but the sonochemical method proceeds under less basic conditions. Both methods preserve the integrity of the asymmetric center. 

Miscellaneous Transformations. Cyanotrimethylsilane effects the transformation of acyl chlorides to acyl cyanides, a-chloro ethers and a-chloro thioethers to a-cyano ethers and a-cyano thioethers (eq 19), t-butyl chlorides to nitriles (eqs 20 and 21), 1,3,5-trisubstituted hexahydro-l,3,5-triazines to amino-acetonitriles, the cyanation of allylic carbonates and acetates (eqs 22 and 23), and the formation of aryl thiocyanates from aryl sulfonyl chlorides and sulfinates. The reagent has been used effectively in peptide synthesis and in a range of other synthetic applications. " ... 

Propargylic Anion Equivalent. (TMS)allene reacts with electrophiles at the C-3 position in an Se2 process analogous to electrophilic substitution reactions of allyl- andpropargylsilanes. For example, upon treatment with trimethylsilyl chlorosulfonate or sulfur trioxide-1,4-dioxane, (TMS)allene yields silyl esters of sulfonic acids (eq 3). (TMS)allene undergoes conjugate addition with a, 8-unsaturated acyl cyanides to yield 5,e-acetylenic acyl cyanides. ... 

Although allylic silanes fail to react with a,/3-ethylenic esters, conjugate addition to a,/3-ethylenic acyl cyanides occurs quantitatively under the influence of titanium tetrachloride to give 5,e-ethylenic acyl cyanides, acids, or esters, depending on the work-up procedure (e.g. Scheme 68)/ Allenic silanes react in an analogous way to give the corresponding 5,e-acetylenic compounds. 

Oxidation of 101 to ester 2 and epoxidation of the sterically most accessible olefin, completed the synthesis of CJH. The conversion of 101 to 2 is notable, and relies on the selective oxidation of allylic alcohols to aldehydes by manganese dioxide. The sequence of events is (1) oxidation of 101 to the corresponding aldehyde, (2) cyanohydrin formation, (3) oxidation of the cyanohydrin to an acyl cyanide and (4) methanolysis of the acyl cyanide to provide the ester. 

Methoxyoxazolidines 526 are useful for the asymmetric formylation of various nucleophiles including silyl enol ethers, trimethylsilyl cyanide, enamines, and allyl silanes. The reaction of nucleophiles with 2-alkyl-2-methoxyoxazo-lidines offers a general method for asymmetric acylation. 

Similarly, Shono studied the diastereoselective introduction of the allyl group into the 5-position of A/ -acylated L-proline derivatives by reaction of the N,0-aceia with allyltrimethylsilane in the presence of titanium tetrachloride [214]. Substitution of the anodically introduced methoxy group by cyanide using trimethylsilyl cyanide [215,216] or an isocyanide [217] as the nucleophile can be used to generate a-amino acids via hydrolysis of the cyano function. Equation (41) shows an example [216]. 

TiCU or BFs -OEt2-catalyzed addition of A)-acylated aromatic aldimine to triiso-propylallylsilane gives azetidine derivatives 202 (equation 166) accompanied by some allylated products . Cycloaddition of aUylsilanes and chlorosulfonyl isocyanate yields the silyl-substituted yS-lactam 203 . The presence of an electronegative substituent on the silicon will induce ring opening and fragmentation to yield allyl cyanides 204 (equation 167) . ... 

The synthesis of aldehyde 212 started with an Evans alkylation of the known acylated oxazolidinone 215 with allyl iodide 216 to form the corresponding alkylated product 217 as a single diastereoisomer in 81% yield (Scheme 2.88) [118]. Reductive removal of the chiral auxiliary followed by tosylation of the resulting primary alcohol, cyanide substitution, and reduction with DIBAL... 

---