Asymmetric Strecker-type reactions

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). 

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... 

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. 

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... 

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

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. 

Takamura, M., Hamashima, Y., Usuda, H., Kanai, M., Shibasaki, M. A catalytic asymmetric Strecker-type reaction promoted by Lewis acid-Lewis base bifunctional catalyst. Chem. Pharm. Bull. 2000,48, 1586-1592. 

The bifunctional Lewis acid-Lewis base catalyst 55 has been applied with success to the asymmetric Strecker type reaction [61] (Table 8). 

Example 5, Asymmetric Strecker-Type Reaction of Nitrones ... 

The Strecker reaction starting from an aldehyde, ammonia and a cyanide source is an efficient method for the preparation of a-amino acids and their derivatives. A popular version for asymmetric purposes is based on the use of preformed imines and a subsequent nucleophilic addition of HCN or TMSCN in the presence of a chiral catalyst. An intense investigation of the asymmetric Strecker-type reaction has continued over many years, due to the importance of a-amino acid building blocks in medicinal chemistry. Interestingly, a number... 

Hydrocyanation to imines with HCN, the Strecker reaction, is one of the most direct and efficient methods for natural and unnatural a-amino acids. Asymmetric Strecker-type reaction with chiral aluminum Lewis acids has been developed. As shown in Scheme 6.48, the research group of Jacobsen reported chiral Al(salen)Cl complex (67a) as an effective asymmetric catalyst for catalytic enantioselective Strecker reaction of aromatic N-allylimines with HCN [62]. Compared to the reactions of aromatic imines, that of a-branched aliphatic imines (R = Cy and t-Bu) gave Strecker products in only moderate optical yield. Additionally, the use of TMSCN instead of HCN dramatically reduced in the enantioselectivity. 

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