Ketones trimethylsilyl cyanide

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]... 

Treatment of a-(benzotriazol-l-yl)alkyl thioethers 831 with ZnBr2 weakens the bond with benzotriazole, and the obtained complex 832 may partially dissociate to thionium cation 835 that can be trapped by even mild nucleophiles. Thus, trimethylsilyl cyanide added to the reaction mixture causes substitution of the benzotriazole moiety by the CN group to give a-(phenylthio)carbonitrile 834. In a similar manner, treatment with allylsilane leads to y,S-unsaturated thioether 833. Addition of species 835 to the double bond of a trimethylsilyl ot-arylvinyl ether followed by hydrolysis of the silyloxy group furnishes (i-(phenylthio)alkyl aryl ketones 836 (Scheme 132) <1996TL6631>. 

Cyanation of aldehydes and ketones is an important chemical process for C C bond formation." " Trimethylsilyl cyanide and/or HCN are commonly used as cyanide sources. The intrinsic toxicity and instability of these reagents are problematic in their applications. Acetyl cyanide and cyanoformates were used as cyanide sources in the enantioselective cyanation of aldehydes catalyzed by a chiral Ti complex and Lewis base (Scheme 5.31)." The Lewis base was necessary for the good yields and selectivities of these reactions. The desired products were obtained in the presence of 10mol% triethyl amine and 5mol% chiral titanium catalyst (Figure 5.14). Various aliphatic and aromatic aldehydes could be used in these reactions. 

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-... 

Cyanosilylation of methyl ketones has been carried out using diphenylmethylphos-phine oxide and trimethylsilyl cyanide, generating a phosphorus isonitrile-type species, Ph2MeP(OTMS)(N=C ), as the reactive intermediate.271 A chiral oxazaborolidinium ion catalyst renders the reaction enantioselective. 

Trimethylsilyl cyanide is a useful reagent for the preparation of /8-amino alcohols,2 a-amino nitriles,3 and a-trimethylsiloxyacrylo-nitriles4 from the corresponding ketones, imines, and ketenes. The reagent adds rapidly to the carbonyl of aldehydes at 25°C,2 and the resulting adducts have proven useful precursors for the preparation of carbonyl anion synthons.5 Enones give exclusively the products derived from 1,2-addition.2... 

A general method for the preparation of a-cyano ketones from acid halides was developed recently (equation 43).i57.i58 trimethylsilyl cyanide as reagent a great number of acyl cyanides can be prepared under mild conditions in high yield. In particular the synthetically useful aliphatic derivatives have become accessible by this reaction. Table 13 lists examples for aliphatic, a, -unsaturated and benzylic acyl cyanides. The procedure is very simple in that trimethylsilyl cyanide and acid chloride are mixed and kept without solvent. The reaction is followed by IR spectroscopy. As soon as all of the trimethylsilyl cyanide is consumed, the product can be isolated, normally by distillation, or directly used for fruther reactions. 

Trimethylsilyl cyanide. 13, 87-88 14,107 15,102-104 17,89 18,381-382 19,375 fi-Trimethylsiloxy nitriles. The TiCl -promoted epoxide opening is subject to asymmetric induction by chiral ligands. The derivatization of aryl ketones is efficiently promoted by LiClO and LiBF. For safety consideration the use of LiBF /MeCN is recommended. 

Optically pure cyanohydrins serve as highly versatile synthetic building blocks [24], Much effort has, therefore, been devoted to the development of efficient catalytic systems for the enantioselective cyanation of aldehydes and ketones using HCN or trimethylsilyl cyanide (TMSCN) as a cyanide source [24], More recently, cyanoformic esters (ROC(O)CN), acetyl cyanide (CH3C(0)CN), and diethyl cyanophosphonate have also been successfully employed as cyanide sources to afford the corresponding functionalized cyanohydrins. It should be noted here that, as mentioned in Chapter 1, the cinchona alkaloid catalyzed asymmetric hydrocyanation of aldehydes discovered... 

Greenlee, W.J., and Hangauer, D.G., Addition of trimethylsilyl cyanide to a-substituted ketones. Catalyst efficiency, Tetrahedron Lett., 24, 4559, 1983. 

Trimethylsilyl cyanide reacts with ketones and aldehydes in the presence of a Lewis acid catalyst to afford trimethylsilyl ethers of cyanohydrins (eq (36)) [33]. 

Regiosp>ecific synthesis of enol silyl ethers can also be achieved from enones either by reductive silylation or by 1,4-addition of the conjugated system. Thus, Li/NH reduction of the decalone (27) and silylation give the enol silyl ether (28). Similarly, addition of lithium dimethylcuprate to cyclohexenone followed by silylation gives the enol silyl ether (29). Trimethylsilyl cyanide (30) normally adds 1,2 to conjugated ketones (e.g. carvone, 31). However, in the presence of trialkylaluminum, 1,4-addition bdces place to give the enol silyl ether (32 Scheme 9). The same overall transformation can be accomplished by diethylaluminum cyanide and trimethylchlorosilane. ... 

In an extension of the addition of trimethylsilyl cyanide to aldehydes and ketones, it was found that the combination of trimethylsilyl cyanide and lithium cyanide in tetrahydrofuran adds to these systems in high yield27. The lithium ion must serve as a catalyst in this reaction, eliminating the need for the zinc chloride that is ordinarily used for this purpose (equation 20). 

Enones can be reduced to the saturated ketones with triethylsilane and Wilkinson s catalysis62 (equation 54). Interestingly, the same product was prepared via a Tiffeneau-Demjanov ring expansion wherein trimethylsilyl cyanide was used (equation 55). The selective reduction of the double bond of enones can also be carried out with diphenylsilane in the presence of palladium(O) or palladium(II) and zinc chloride63 (equation 56), or more effectively with phenylsilane and molybdenum hexacarbonyl64 (equation 57). This latter reagent was also used to reduce the double bond of a,/ -unsaturated esters, amides and nitriles. 

Cyanosilylation of ketones (4,542-543 5,720). In a total synthesis of natural camptothecin (9), Corey et al used this f-butyldimethylsilyl derivative rather than trimethylsilyl cyanide (5, 720-722) to effect cyanosilylation of a ketone (1). Hydrolysis of the resulting cyano silyl ether to the required amide was not accompanied by desilylation with reversal of cyanohydrin formation. By use of carefully controlled conditions and with dicyclohexyl-18-crown-6-potassium cyanide as catalyst, they were able to convert (1) into the a-hydroxy... 

KETONES f-Butyl a-lithioisobutyrate. Benzoin. Chlorocarbonylbis(triphenylphosphine)-rhodium(I). m-Chloroperbenzoic acid. Chromic acid. Dimethylcopperlithium. Diphenyl disulfide. Formaldehyde diphenyl thioacetal. Methylthioacetic acid. Sodium cyanide. Tetrakis triphenylphosphine)palladium(0). Trimethylchlorosilane. Triphenyl-methyl isocyanide. Trimethylsilyl cyanide. 

Treatment of aldehydes and trimethylsilyl cyanide (TMSCN) in toluene at —78 °C in the presence of the catalytic amount of symmetrical bicyclic guanidine 13 smoothly afforded an (5)-excess adduct with good to moderate ee [37]. (Table 4.3) A ketonic 3-phenyl-2-butanone can work as an acceptor under the above conditions, but reactivity is low (23% yield, 39% ee). 

The mono-silyl ether (49) was also produced on attempted formation of the trimethylsilyl cyanohydrin ether of the 37-ketone function of pristinamycin 11, using trimethylsilyl cyanide/zinc iodide according to the procedure of D. Evans and co-workers [116]. 

More recently, it has been found that trimethylsilyl cyanide reacts with ketones to... 

Trimethylsilyl cyanide, which forms stable adducts of ketones which do not form cyanhydrins, reacts with 4-t-butylcyclohexanone in the presence of Znlj to give... 

An improved preparation of p-aminomethyl alcohols from ketones has been developed using trimethylsilyl cyanide followed by lithium aluminium hydride reduction. It is particularly useful for ocp-unsaturated ketones and for relatively hindered ketones, and should make the Tiffeneau-Demjanov ring-expansion procedure more attractive. ... 

A few drug discovery synthesis routes were used to diversify the thiohydantoin structures. The first route exploited a convergent concept where a three-component Strecker reaction of an amine, a ketone and trimethylsilyl cyanide was used to generate (he cyanoamine analog 24 (Scheme 1). Isothiocyanate prepared from the amine with thiophosgene was added to the cyanoamine to give thiohydantoin -imine 25 which was hydrolyzed to afford the desired thiohydantoins 26. 

M-unsubsituted thiohydantoin 29 was prepared from the ketone with anhydrous ammonia and trimethylsilyl cyanide (Scheme 2). The 1-amino carbonitrile 27 was treated with isothiocyanate to form thiohydantoin-4-imine 28, followed by hydrolysis to produce M-unsubsituted thiohydantoins 29. These intermediates were subjected to an SnAt reactions with several 4-halo-aromatic derivatives, such as 4-fluorocyanobenzene, to afford a series of M-aromatic group-substituted thiohydantoins 30. 

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