Trimethylsilyl cyanide , Strecker amino acid synthesis

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%. 

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. 

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. 

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