Strecker-type reaction

Like the nitronate ion, the cyanide ion is synthetically equivalent to the aminomethyl carbanion (CH2NH2) , because of the possible reduction of - CN to the - CH2NH2 group. Consequently, the addition of cyanide ion to imines to give a-aminonitriles (Strecker-type reaction) is a viable route to 1,2-diamines. As a matter of fact, a number of diastereoselective and catalytic... 

The asymmetric Strecker-type reaction developed by the Jacobsen group is suitable for both aUphatic and aromatic imines, giving high enantiomeric excesses for a wide range of substrates. In this reaction the urea derivative also acts as the catalyst (Scheme 36). 

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. 

Moreover, it seemed to be a rational extension to apply the catalyst 123 to the asymmetric Strecker-type reaction.1291 Actually, as shown in Table 13, an efficient and general catalytic asymmetric Strecker-type reaction has been realized. Products were successfully converted to the corresponding amino acid derivatives in high yields without loss of enantiomeric purity.1301... 

Table 13. Asymmetric Strecker-type reaction of imines catalyzed by 123.

Shibasaki, A Catalytic Asymmetric Strecker-type Reaction Interesting Reactivity Difference between TMSCN and HCN, Angew. Chem Int. Ed. Engl. 2000,39,1650-1652... 

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). 

Yet L (2001) Recent developments in catalytic asymmetric Strecker-type reactions. Angew Chem Int Edit 40(5) 875-877... 

Asymmetric Cyanation of C=N Bonds (Strecker-Type Reaction). . 121... 

Strecker-type reaction of TMS cyanide with chiral sulfinimines gives diastereoselective cyanations at the imine carbon, at —78 °C in DMF, using simple metal-free Lewis base catalysts such as tetraalkylammonium carboxylates.73... 

Recent Developments in Catalytic Asymmetric Strecker-Type Reactions... 

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. 

Sigman and Jacobsen reported the first example of a metal-catalyzed enantioselective Strecker-type reaction using a chiral Alnl-salen complex (salen = N,N -bis(salicyhdene)-ethylenediamine dianion) [4]. A variety of N-allylimines 4 were evaluated in the reaction catalyzed by complex 5 to give products 6, which were isolated as trifluoroacetamides in good yields and moderate-to-excellent enantioselectivities (Scheme 3). Substituted arylimines 4 were the best substrates, while alkyl-substituted imines afforded products with considerably lower ee values. Jacobsen and co-workers also reported that non-metal Schiff base catalysts 8 and 9 proved to be effective in the Strecker reaction of imines 7 with hydrogen cyanide to afford trifluoroacetamides 10 after reaction with trifluoroacetic anhydride, since the free amines were not stable to chromatography (Scheme 4) [5]. 

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... 

Lewis acid and the oxygen atom of the phosphane oxide, respectively. With this catalyst system, N-allyl- and N-benzhydrylimines generally gave lower enantioselectivities. The addition of phenol was found to have a beneficial effect on the reaction rates. The JandaJEL -supported bifunctional catalyst of 14 has also been shown by Shibasaki and co-workers to promote the Strecker-type reaction of aromatic and a,/ -unsaturated imines in excellent yields with 83-87% ee in the presence of tert-butanol (110%) [11]. The reactivity of the Janda/EL catalyst was comparable to the homogeneous analogue 14, and the catalyst could be recycled at least four times. 

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%... 

L. Yet, Recent Developments in Catalytic Asymmetric Strecker-Type Reactions, Angew. Chem. Int. Ed. 2001, 40, 875-877. 

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. 

The above set of reactions constitutes a particularly striking demonstration of the potentiaiities of the Strecker-type reactions four valuable chemicals arc selectively obtained from the same cheap and simple reagents. 

Several examples of the Strecker-type reaction were tested. For all the compounds investigated, including aromatic, aliphatic, heterocyclic, and aj3-unsaturated aldehydes, the reactions proceeded smoothly to afford the corresponding a-amino nitriles in high yield. The adducts, a-(A-benzhydryl)amino nitriles, were readily converted to a-amino acids [78], and Strecker-type reactions using other amines such as aniline and benzylamine also proceeded smoothly to afford the corresponding adducts in high yields. 

Scheme 9. Recycle system of the novel Strecker-type reaction.

Aromatic and aliphatic aldehydes in the presence of dialkylamines and an equivalent of acid such as hydrochloric, perchloric or p-toluenesulfonic acid give iminium salts, which add cyanide ion to form a-(dialkylamino)nitriles. An alternative preparation involves the reaction of the aldehyde with dialkylamines in the presence of acetone-cyanohydrin, a-(A, -dialkylamino)isobutyronitiiles, diethyl phosphorocyanidate or TMS-CN. Another route to a-aminonitrile starts with an aldehyde, the salt of an amine and KCN in organic solvents under solid-liquid two-phase conditions by combined use of alumina and ultrasound. Chiral a-aminonitriles were prepared by Strecker-type reactions, cyano-silylation of Schiffs bases, amination of a-siloxynitriles or from an A -cyanomethyl-l,3-oxazolidine synthon. Reaction of tertiary amines with CIO2 in the presence of 5.1 mol equiv. of aqueous NaCN as an external nucleophile affords a-aminonitrile. °... 

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. 

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