Trimethylsilyl cyanide , Strecker

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%. 

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. 

Strecker reactions provide one of the most efficient methods for the synthesis of a-amino nitriles, which are useful intermediates in the synthesis of amino acids and nitrogen-containing heterocycles. Although classical Strecker reactions have some limitations, use of trimethylsilyl cyanide (TMSCN) as a cyano anion source provides promising and safer routes to these compounds.133-351 Consequently, we focused our attention on tributyltin cyanide (Bu3SnCN), because Bu3SnCN is stable in water and is also a potential cyano anion source. Indeed, the Strecker-type reactions of aldehydes, amines, and Bu3SnCN proceeded smoothly in water (Eq. 9).1361 It should be noted that no surfactants are required in this reaction. Furthermore, Complete recovery of the toxic tin compounds is also possible in the form of bis(tributyltin) oxide after the reaction is over. Since conversion of bis(tributyltin) oxide to tributyltin cyanide is known in the literature, this procedure provides a solution to the problem associated with toxicity of tin compounds. 

Starting from levulinic acid, it was possible to obtain 8a-substituted-4-phenyltetrahydro-l//-pyrrolo[2,l-c][l,4]oxa-zinc-1. />(7//)-dioncs 170 (Scheme 26) via Strecker reaction. Compound 171 was treated with 1 equiv of sodium hydroxide and the salt reacted with (f )-phenylglycinol to give a mixture of the Schiffs base 172 and the 1,3-oxazolidine 173 that was reacted with trimethylsilyl cyanide. Further treatment with HCl-saturated methanol afforded a mixture of 174 and 175. Heating at 200 °C in a sealed tube provided 170 as two separable isomers in 73% and 10% yields, respectively <1999TL5753>. 

In 1987 Kunz [32] reported the use of 2,3,4,6-tetra-0-pivaloyl-/ -D-galactopyrano-sylamine 27 as chiral auxiliary in the preparation of a-aminoacid derivatives via the Strecker reaction with aldehydes and trimethylsilyl cyanide. One year later he reported [33, 34] the use of the same chiral auxiliary in the Ugi reaction, where trimethylsilyl cyanide was replaced by an isocyamde and a carboxylic acid (Scheme 1.12). 

Shibasaki and co-workers disclosed a general asymmetric Strecker-type reaction that was controlled by bifunctional Lewis acid-Lewis base catalyst 14 [10], N-Fluorenylimines 15 underwent catalytic asymmetric Strecker-type reactions with binaphthol catalyst 14 to give a-aminonitriles 16 in good to excellent enantioselectivities and yields (Scheme 6). a-Aminonitrile 16 (R = Ph) could then be converted to a-aminoamide 17 in several steps. Aromatic, aliphatic, heterocyclic and a,/f-unsaturated imines 15 were used as general substrates in these reactions. The origin of the highly enantioselective cataylsis by 14 is believed to be attributed to the simultaneous activation of imines and trimethylsilyl cyanide by the... 

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]. 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

The only known metal catalyst for the asymmetric catalytic Strecker reaction is the aluminum salen catalyst 465 (Sch. 65) recently reported by Sigman and Jacobsen [97]. They prepared 11 different chiral salen complexes from different transition and main group metals and screened these complexes for the addition of trimethylsilyl cyanide to imine 460 at room temperature. The aluminum catalyst 465 was optimum in terms both of asymmetric induction and rate. This constitutes the first aluminum salen complex successfully developed for an asymmetric catalytic reaction. 

Enders, D., Moser, M. Asymmetric Strecker synthesis by addition of trimethylsilyl cyanide to aldehyde SAMP-hydrazones. Tetrahedron Lett. 2003,44, 8479-8481. 

Fetterley et al. have been very active in determining the utility of strongly basic PAPT-type reagents in organic synthesis, and have reported that a-aminonitrile compounds could be efficiently synthesized by the Strecker condensation of aldehydes, amines, and trimethylsilyl cyanide (TMSCN) in the presence of a nitrate salt of PS-PAPT as a catalyst [34] (Scheme 6.5). In this work, the reusability of the catalyst was also established, and the catalyst activity was ascribed to the participation of a nitrate ion of the catalyst acted as a proton shuttle. ... 

The Strecker reaction that is the nucleophilic addition of trimethylsilyl cyanide (TMSCN) to imines in water has been developed in the presence of P-CD to afford a-aminonitriles (Figure 4.15a). The use of CD precludes the use of either acid or base, and the catalyst can be recycled a number of times without loss in activity. No reaction... 

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. 

Strecker reaction using trimethylsilyl cyanide (TMSCN) as cyanide source under mild conditions, affording good yield for the final a-aminonitriles 59. The small catalytic charge used in this process is also notable (Scheme 10.16) [56]. 

E. Takahashi, H. Fujisawa, T. Yanai, T. Mukaiyama, Chem. Lett. 2005, 34, 318-319. Lewis hase-catalyzed Strecker-type reaction between trimethylsilyl cyanide and iV-tosyhmines in water-containing DMF. 

Sc(BINOL)2Li, a new chiral heterobimetallic complex, was shown to catalyze addition of a cyanide source (hydrogen cyanide (HCN) and trimethylsilyl cyanide (TMSCN)) to various imines enantioselectively [128]. Moderate to high conversions and enantiomeric excesses were obtained in this Strecker reaction using 10 mol% of the catalyst. High enantioselectivity (84% ee) and quantitative yield were also obtained by the addition of TMSCN to benzaldehyde. 

Trimethylsilyl-protected 1-ethoxycyclopropanol 30 also reacts with hydrochlorides of primary amines under Strecker conditions to give adducts of the amines and cyclopropanone. However, due to the presence of sodium cyanide in the medium, the intermediate hydroxyamines were... 

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