Cyanide trimethylsilyl

The allylic geminal diacetate 141 undergoes the monoallylation of malonates to give 142 and the two regioisomers 143 and 144[93,94]. The dimethylacetal 145 or ortho esters of aromatic and a,/3-unsaturated carbonyl compounds react with trimethylsilyl cyanide to give the methyl ether of cyanohydrin[95]. 

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]. 

The cyanosilylation of alkynes with trimethylsilyl cyanide proceeds by either Pd or Ni catalysis to give 182[99]. When an excess of trimethylsilyl cyanide is used, the 5-aminopyrrole-2-carbonitrile 183 is obtained[100,101]. 

The reaction of phenylmethylenecyclopropane with trimethylsilyl cyanide catalyzed by PdCl2 affords the allylsilane 81 in 71% yield[63]. 

In the presence of strongly acidic media, such as triflic acid, hydrogen cyanide or trimethylsilyl cyanide formylates aromatics such as ben2ene. Diprotonotated nittiles were proposed as the active electrophilic species in these reactions (119). 

Methylpyridazine gives the pyridazine Reissert compound (105) with trimethylsilyl cyanide and freshly distilled benzoyl chloride. On the other hand, when pyridazine or 3-methylpyridazine reacts with undistilled benzoyl chloride the bicyclic compounds (106) are formed and these react with dimethyl acetylenedicarboxylate in anhydrous DMF to give pyrrolopyridazine derivatives (107 Scheme 30) (81JHC443). 

Trimethylsilyl cyanide. This reagent readily silylates alcohols, phenols, and carboxylic acids, and more slowly, thiols and amines. Amides and related compounds do not react with this reagent. The reagent has the advantage that a volatile gas (HCN is highly toxic) is the only byproduct. 

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. 

Another useful reagent for the preparation of alkynyl lodonium Inflates is [cyano(trifluoromethylsulfonyloxy)(phenyl)]iodine [/i7, 138, 139, 140] prepared from iodosobenzene, trimethylsilyl tnflate, and trimethylsilyl cyanide (equation 71). This reagent reacts with various stannylacetylenes under very mild conditions to form the corresponding alkynyl iodonium salts in high yields [139] (equation 72)... 

The reaction works well with primary alkyl halides, especially with allylic and benzylic halides, as well as other alkyl derivatives with good leaving groups. Secondary alkyl halides give poor yields. Tertiary alkyl halides react under the usual reaction conditions by elimination of HX only. Nitriles from tertiary alkyl halides can however be obtained by reaction with trimethylsilyl cyanide 4 ... 

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%. 

Method A 2.7 g (20 mmol) of zinc chloride are dried in vacuo (0.01 Torr) at 200 C for 2 h. After cooling to 0 C, 150 mL of /-PrOH, 2.4 g (20 mmol) of trimethylsilyl cyanide and, subsequently, 15 mmol of the iV-galactosylimine dissolved in 50 mL of /-PrOH. are added within 15 min. The mixture is stirred for 1.5 h at 0 C, and then allowed to warm to r.t. After evaporation of the solvent in vacuo, the residue is taken up in a mixture of 150 mL of CH,C12 and 100 mL of 1 N HCI acid. The organic layer is extracted with two 100-mL portions of sat. NaHCO, then with water, dried with MgS04 and concentrated in vacuo. The crude product is analyzed by HPI.C. Recrystallization from heptane delivers the pure (R)-diastcrcomcr. 

Interestingly, the diastereofacial selectivity can be reversed in the Strecker reaction of aldimines derived from galactosylamine 1 by simply changing the solvent. When the reaction of trimethylsilyl cyanide with the Schiff bases 2 catalyzed by zinc chloride, is carried out in chloroform instead of 2-propanol, there is a preferred formation of the (.S)-amino nitrile diastereomers63. 

THF THP TIPS TIPSOTf TMEDA TMS TMSC1 TMSCN TMS I TMSOTf Ts tetrahydrofuran tetrahydropyranyl tri-isopropylsilyl tri-isopropylsilyl trifluoromethanesulphonate AVV,N N -tetramethylethylenediamine trimethylsilyl trimethylsilyl chloride (chlorotrimethylsilane) trimethylsilyl cyanide (cyanotrimethylsilane) trimethylsilyl iodide (iodotrimethylsilane) trimethylsilyl trifluoromethanesulphonate tosyl (p-tolucnesulphonyl)... 

A completely different way of preparing isocyanides involves the reaction of epoxides or oxetanes with trimethylsilyl cyanide and zinc iodide, for example, ... 

Pd(0) complex, or with KCN and a Ni(0) catalyst. Halides can be converted to the corresponding nitriles by treatment with trimethylsilyl cyanide in the presence of catalytic amounts of SnCl4 R3CCI + Me3SiCN —> R3CCN. ... 

Thus removal of water from classical rather inactive fluoride reagents such as tetrabutylammonium fluoride di- or trihydrate by silylation, e.g. in THF, is a prerequisite to the generation of such reactive benzyl, allyl, or trimethylsilyl anions. The complete or partial dehydration of tetrabutylammonium fluoride di- or trihydrate is especially simple in silylation-amination, silylation-cyanation, or analogous reactions in the presence of HMDS 2 or trimethylsilyl cyanide 18, which effect the simultaneous dehydration and activation of the employed hydrated fluoride reagent (cf, also, discussion of the dehydration of such fluoride salts in Section 13.1). For discussion and preparative applications of these and other anhydrous fluoride reagents, for example tetrabutylammonium triphenyldifluorosilicate or Zn(Bp4)2, see Section 12.4. Finally, the volatile trimethylsilyl fluoride 71 (b.p. 17 °C) will react with nucleophiles such as aqueous alkali to give trimethylsilanol 4, HMDSO 7, and alkali fluoride or with alkaline methanol to afford methoxytri-methylsilane 13 a and alkali fluoride. 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Reactions of Heterocyclic N-Oxides with Trimethylsilyl Cyanide, Trimethylsilyl Azide, Trimethylsilyl Isothiocyanate, and Trimethylsilyl Halides... 

It is obvious that the combination of trimethylsilyl cyanide 18/DBU reacts faster than the combination 18/NEt3. The higher boihng and more polar acetonitrile is. 

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