Catalytic Asymmetric Strecker Reactions

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... 

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). 

Optically active a-amino acids are prepared by a cyanide addition to imines, known as the Strecker reaction. Several organobase catalysts and metal complex catalysts have been successfully applied to the asymmetric catalytic Strecker amino... 

Representative metal complexes employed for the catalytic asymmetric Strecker reaction are summarized in Figure 4.2. Aluminum-, titanium-, lanthanoid-, and zirconium-based catalysts are highly efficient. Direct one-pot synthesis starting from aldehydes, and amines is reported using the Zr complex described in Figure 4.2. ... 

One of the most important approaches to a-amino acids is based on the Strecker reaction. Although there are already a number of catalytic asymmetric variants, the cyanation of imines still challenges modem organic chemists. 

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

Tsogoeva and co-workers explored the catalytic potential of pyridyl- and imida-zoyl-containing thiourea derivatives (e.g., thiourea 92 and 93) in the asymmetric model Strecker reactions [157] of N-benzyl- and benzhydryl-protected benzaldi-mine with HCN [258], The observed enantioselectivities were consistently very low (4—14% ee) for all catalyst candidates and were far below synthetically useful levels, while imidazoyl-thiourea 93 was reported to be highly active and displayed 100% conversion (at 7% ee) of the N-benzhydryl-protected benzaldimine (Scheme 6.99). X-ray structure analysis of a pyridyl-thiourea revealed an intramolecular hydrogen-bond between the basic ring nitrogen and one amide proton. This could make this... 

The cyanation of imines, generally known as the Strecker reaction, has been one of the most aggressively studied transformations of asymmetric catalysis over the past several years. Very recent efforts in this area have resulted in the discovery of several highly efficient catalytic systems capable of providing a-ami-... 

The wide assortment of catalytic asymmetric Strecker reaction methodologies devised to date can be divided into two major categories based on the nature of catalyst utilized 1) Lewis acid-promoted and 2) metal-free (or organo-catalytic) systems. Both classes of catalysis will be discussed and key results will be highlighted. 

The potential substrates for the Strecker reaction fall into two categories ald-imines (derived from aldehydes, for which cyanide addition results in formation of a tertiary stereocenter) and ketoimines (derived from ketones, for which addition results in a quaternary stereocenter). As in the case of carbonyl cyanation, significant differences are observed between the substrate subclasses. To date, while a few catalyst systems have been found to display broad substrate scope with respect to aldimine substrates, successful Strecker reactions of ketoimines have been reported in only two cases. As is the case for all asymmetric catalytic methodologies, the breadth of the substrate scope constitutes a crucial criterion for the application of the Strecker reaction to a previously unexplored substrate. 

Table 1. Overview of the methods for the catalytic asymmetric Strecker reaction... 

A large number of catalytic asymmetric MCR are based on deoxo-bisubstitution reactions of carbonyl compounds such as the Mannich and Strecker reactions in which an oxo-group is displaced by two new cr-bonds, one to a nitrogen atom and one to a carbon atom. Other examples of deoxo-bisubstitutions include tandem processes that involve an initial Knoevenagel condensation followed by either a nucleophilic or a cycloaddition. These processes are characterized by the conversion of a C O-K-bond into two new C-C-cr-bonds and have been termed carba-acetalizations. 

The first catalytic asymmetric Strecker reaction was reported by the Upton group using the cyclic dipeptide 5 as an organocatalyst [4, 5, 15]. This diketopiperazine 5 was prepared starting from (S)-phenylalanine and (S)-a-amino-y-guanidinobutyric... 

The asymmetric catalytic Strecker reaction is an elegant means of synthesis of optically active a-amino acids. The Jacobsen group developed optimized organocata-lysts [21, 44-48], optically active urea or thiourea derivatives, which were found to be the most efficient type of catalyst yet for asymmetric hydrocyanation of imines (see also Section 5.1 on the hydrocyanation of imines). Because of its high efficiency, Jacobsen hydrocyanation technology has already been used commercially at Rodia ChiRex [49]. The concept of the reaction is shown in Scheme 14.7. In the presence of a catalytic amount (2 mol%) of the readily available organocatalyst... 

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... 

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