Trimethylsilyl cyanide additions

A more recent synthesis by our group utilized Mukaiyama s trimethylsilyl cyanide addition to aldehydes as the key step to introduce the carboxy functionality [33,36], This approach also required the preparation of (Z)-5-pentadecenal as the key intermediate, Fig. (12). In this case, commercially available decyl aldehyde was coupled with 4-carboxybutyltriphenylphosphonium bromide under Wittig conditions, resulting in a 10 1 mixture of the known (Z)- and ( )-5-pentadecenoic acids. The acids were then reduced to the desired (Z)-5-pentadecenal via (Z)-5-pentadecen-l-ol, a known pheromone. Addition of trimethylsilyl cyanide to (Z)-5-pentadecenal, under triethylamine catalysis, yielded... 

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>. 

For more information about the asymmetric addition of trimethylsilyl cyanide to aldehydes, see Belokon et al.151... 

For other catalytic asymmetric cyanosilylation of aldehydes, see C.-D. Hwang, D.-R, Hwang, B.-J. Uang, Enantioselective Addition of Trimethylsilyl Cyanide to Aldehydes Induced by a New Chiral TiflV) Complex, J. Org Chem 1998,63,6762-6763, and references tited therein. 

This technique also greatly improves yields of conjugate addition of cuprates to y..[>-unsaturated esters and amides.38 Trimethylsilyl cyanide also accelerates conjugate addition.39... 

The Reissert reaction of 3,4-dihydro-p-carboline (213) has also been studied 47,48). It has been shown that 3,4-dihydro-p-carboline (213) afforded 1-cyano-2,9-dibenzoyl-l,2,3,4-tetrahydro-P-carboline (214) with a phase-transfer catalyst and trimethylsilyl cyanide (Scheme 27). However, the normal Reissert product 2-benzoyl-l-cyano-l,2,3,4-tetrahydro-p-carboline (215) was obtained when a catalytic amount of anhydrous aluminum chloride was used in addition to the trimethylsilyl cyanide reagent. Reaction of 214 with sodium... 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of haIides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsilyl cyanide in EtjN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Usually the products of Cj-elongation are intermediates, rather than the target amino sugars. The elongation can be repeated iteratively [20]. Cyanohydrin formation belongs to the most typical C,-elongation processes. Addition of trimethylsilyl cyanide to a-amino aldehydes of type 1 in the presence of Lewis acid yielded a mixture of diastereoisomers 2 and 3 [21] (Scheme 3). 

A binaphthol-modified Ti(IV) complex effects enantioselective addition of trimethylsilyl cyanide to aldehydes to form optically active cyanohydrin derivatives (Scheme 124). The highest ee value of 82% is achieved in the reaction of isovaleraldehyde with 20 mol % of the catalyst (286a). Use of a tartrate-derived modifier in combination with molecular sieves 4A is also effective for this type of addition and results in... 

Cyanohydrin derivatives have also been widely used as acyl anion synthons. They are prepared from carbonyl compounds by addition of hydrogen cyanide. A very useful variant is to use trimethylsilyl cyanide with an aldehyde to produce a trimethylsilyloxy cyanide. The cyano group acidifies the a position (pKA 25) and the a proton can be removed by a strong base. Alkylation of the anion and unmasking of the hydroxy group cause elimination of cyanide and re-formation of the carbonyl group. 

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-... 

Two other types of catalysts have been investigated for the enantioselective Strecker-type reactions. Chiral N-oxide catalyst 24 has been utilized in the trimethylsilyl cyanide promoted addition to aldimines to afford the corresponding aminonitriles with enantioselectivities up to 73% ee [14]. Electron-deficient aldimines were the best substrates, but unfortunately an equimolar amount of catalyst 24 was used in these reactions. The asymmetric Strecker addition of trimethylsilyl cyanide to a ketimine with titanium-based BINOL catalyst 25 gave fast conversions to quarternary aminonitriles with enantiomeric excesses to 59%... 

Several reports have employed a more traditional approach where the use of enantio-pure chiral amino auxiliaries, that, after the successful Strecker reaction, can be chemically modified to yield the free amino acids. For example, Chakraborty and co-workers have reported the highly diastereoselective addition of trimethylsilyl cyanide to a variety of a-phenylglycinol-derived benzaldimines [16]. (S)-a-Methylbenzylamine has been used as a chiral auxiliary for the asymmetric Strecker reaction [17]. (R)-Phenylglycinol has been utilized as a chiral auxiliary from the asymmetric Strecker reaction products of aldehydes in the synthesis of a,a-disubstituted amino acids [18]. (R)- and (S)-2-Amino-2-phenylethanol were used as chiral auxiliaries in the synthesis of optically pure a-arylglycines [19]. 

Trimethylsilyl cyanide (0.54 ml, 4 mmol) was added to a stirred suspension of iodosyl triflate (0.58 g, 2 mmol) in dichloromethane (15 ml) at — 78°C under nitrogen. The mixture was allowed to warm to — 20°C and stirred at this temperature for 15 min until the formation of a clear solution. The solution was cooled to — 78°C and transferred to a cold stirred solution of the appropriate tributyltin heterocycle (4 mmol) in dichloromethane (15 ml). The mixture was brought to room temperature and crystallized by the addition of dry hexane (20-30 ml). The precipitated iodonium salt was filtered under nitrogen, washed with dry ether (30 ml) and dried in vacuo. Mono or bis hetaryl iodonium salts prepared by these and related methods also involved groups coming from selenophene [23], pyrazoles [24], benzothiophene [21], etc. 

The selected examples by Cole et al. [120] and Shimizu et al. [121] reported the parallel synthesis of a small library of solid supported dipeptide Schiff bases as ligands for the Ti-catalyzed enantioselective addition of trimethylsilyl cyanide to meso epoxides, and the determination of their catalytic activity on different substrates. The catalyzed addition reaction and the general structure of the dipeptide ligands are shown in Figure 7.15. 

FIGURE 7.15 Ti-catalyzed enantioselective addition of trimethylsilyl cyanide to epoxides, and structure of dipeptide ligands. 

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