Strecker-type synthesis

Shibasaki et al. developed a polymer-supported bifunctional catalyst (33) in which aluminum was complexed to a chiral binaphtyl derivative containing also two Lewis basic phosphine oxide-functionahties. The binaphtyl unit was attached via a non-coordinating alkenyl Hnker to the Janda Jel-polymer, a polystyrene resin containing flexible tetrahydrofuran-derived cross-Hnkers and showing better swelling properties than Merifield resins (Scheme 4.19) [105]. Catalyst (33) was employed in the enantioselective Strecker-type synthesis of imines with TMSCN. 

Scheme 4.19 Asymmetric Strecker-type synthesis of a-amino nitriles.

A clean, Strecker-type synthesis of a-aminonitriles has been developed amine, aldehyde, tributyltin cyanide, and scandium(III) triflate (as catalyst) are mixed together at room temperature. Yields for a range of aliphatic and aromatic aldehydes are typically ca 90%, the solvent can be organic or aqueous, the 10% catalyst loading is recoverable and reusable, and the tin reagent is similarly recyclable. 

Kobayashi and co-workers employed the chiral zirconium binuclear catalyst 22 in the asymmetric Strecker-type synthesis of a-aminonitriles 23 from aldimines 21 with tributyltin cyanide (Scheme 8) [13]. Aldimines 21 were in turn derived from aliphatic, aromatic, and... 

The assymetric Strecker reaction of diverse imines, including aldimines as well as ketoimines, with HCN or TMSCN provides a direct access to various unnatural and natural amino acids in high enantiomeric excesses, using soluble or resin-linked non-metal Schiff bases the corresponding chiral catalysts are obtained and optimized by parallel combinatorial library synthesis [93]. A rather general asymmetric Strecker-type synthesis of various imines and a, 9-unsaturated derivatives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-containing complexes [94]. When chiral (salen)Al(III) complexes are employed for the hydrocyanation of aromatic substituted imines, excellent yields and enatio-selectivities are obtained [94]. 

Amines via condensations. Tryptophan derivatives are obtained by reaction of indoles with A-substituted aziridinecarboxylic esters at 0° or room temperature. Stoichiometric amount of Sc(OTf)3 is required. By SclOTfjj catalysis the Strecker-type synthesis from aldehydes, amines, and BujSnCN can be carried out either in organic solvents or in water. Pictet-Spengler reaction is directly accomplished using acetals. ... 

Addition to C=N bond. Strecker-type synthesis, the addition of MesSiCN to imines, on extending to AT-phosphinoyl ketimines is enantioselective in the presence of 86, and the optimal conditions involve the addition of 10 mol% of MCPBA. ... 

The classical Strecker-type synthesis involving the addition of cyanide to aldehydes, ammonolysis of the cyanohydrin, and hydrolysis of the nitrile, yields racemates. More reactive than the cyanide anion are the azolactones for aromatic aldehydes or acetamido-malonate anions for Michael additions or alkylations (Scheme 9.3.1). 

Soc 75 4090 1953, Beilstein 1 II 111, 1 III 2745, 1 IV 3214.] Trifluoioacetone has been used to prepare trifluoromethylimines of chiral amines in order to prepare R or S enantiopure a-trifluoromethyl alanines, diamines and amino alcohols via a Strecker-type synthesis in a few steps [Huguenot Brigand J Org Chem 71 7075 2006. It has also been used to synthesise 2-trifluon)metltyl-7-azaindoles from 2,6-dihalopyridines [Schirok et al. Synthesis 251 2007],... 

Interestingly, only a few years later, Heilbron and coworkers found that equally good results could be obtained by a simple Strecker-type synthesis. Thus, when the same thioaldehyde was treated with potassium cyanide (KCN) and ammonia, the corresponding a-aminonitrUe resulted and hydrolysis of the cyano group with aqueous hydrochloric acid (HCl) produced methionine (Met, M) (Scheme 12.50). 

K. Iwanami, H. Seo, J.-C. Choi, T. Sakakura, H. Yasuda, Tetrahedron 2010, 66, 1898-1901. Al-MCM-41 catalyzed three-component Strecker-type synthesis of a-aminonitriles. 

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. 

Matsumoto, K. Kim, J. C. Hayasbi, N. Jenner, G. Tetrahedron Lett. 2002, 43, 9167. Yet, L. Recent Developments in Catalytic Asymmetric Strecker-Type Reactions, in Organic Synthesis Highlights V, Scbmalz, H.-G. Wirtb, T. eds., Wiley-VCH Weinbeim, Germany, 2003, pp 187-193. (Review). 

An enantioselective Strecker reaction involving Brpnsted acid catalysis uses a BINOL-phosphoric acid, which affords ees up to 93% in hydrocyanations of aromatic aldimines in toluene at -40 °C.67 The asymmetric induction processes in the stereoselective synthesis of both optically active cis- and trans-l-amino-2-hydroxycyclohexane-l -carboxylic acids via a Strecker reaction have been investigated.68 A 2-pyridylsulfonyl group has been used as a novel stereocontroller in a Strecker-type process ees up to 94% are suggested to arise from the ability of a chiral Lewis acid to coordinate to one of the sulfonyl (g)... 

The Strecker amino acid synthesis, which involves treatment of aldehydes with ammonia and hydrogen cyanide (or equivalents) followed by hydrolysis of the intermediate a-amino nitriles to provide a-amino acids (Scheme 1), was first reported in 1850 [1], This method has been applied on an industrial scale toward the synthesis of racemic a-amino acids, but more recently interest in nonproteinogenic a-amino acids in a variety of scientific disciplines has prompted intense activity in the asymmetric syntheses of a-amino acids [2]. The catalytic asymmetric Strecker-type reaction offers one of the most direct and viable methods for the asymmetric synthesis of a-amino acid derivatives. It is the purpose of this Highlight to disclose recent developments in this emerging field of importance. 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Ma, D., Tian, H., Zou, G. Asymmetric Strecker-type reaction of a-aryi ketones. Synthesis of (S)-aM4CPG, (S)-MPPG, (S)-AIDA, and (S)-APiCA, the antagonists of metabotropic giutamate receptors. J. Org. Chem. 1999, 64,120-125. 

Yet, L. Recent developments in catalytic asymmetric Strecker-type reactions. Organic Synthesis Highlights V 2003, 187-193. 

Huguenot, F. and Brigaud, T. (2006) Concise synthesis of enantiopure a-trifluoromethyl alanines, diamines, and amino alcohols via the Strecker-type reaction.. /. Org. Chem., 71, 7075-7078. 

Since the pioneering work by Ojima et al. [653] the Strecker-type reaction of imines bearing a chiral auxihary with TMSCN has frequently been used for asymmetric synthesis of a-aminonitriles [654]. In recent years catalytic asymmetric hydrocyanation of imines with TMSCN has been intensively studied to establish a more efficient route to optically active a-aminonitriles [655]. 

M. Ayaz, P. De Morales, and C. Hulme, A Carbonyl Compound as ElectrophUic Compound — With an Amine or Analogue as One Nucleophile Component — Third Component Cyanide (Strecker and Strecker-Type Reactions), In T.J.J. MiiUer, editor Multicomponent Reactions 1, Science of Synthesis, Georg Thieme Verlag Stuttgart (2014), p 99. 

Hao and colleagues disclosed a rapid total synthesis of ( )-tr onoliimine A via a Strecker/Houben-Hoesch sequence.The three-component Strecker-type reaction of 169, 170, and TMSCN was found to be effectively promoted by TMSOTf to furnish intermediate 171 this intermediate was unstable in basic or neutral environments and thus was treated directly with triflic acid at room temperature to effect the Houben-Hoesch cyclization and give ketone 172. Finally, the addition of hydrazine triggered deprotection of the amine and subsequent cyclization to furnish 173 (130L528). 

Z. Xie, G. Li, G. Zhao, J. Wang, Synthesis 2009, 2035-2039. Strecker-type reaction catalyzed carboxylic acids in aqueous media. 

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