Strecker catalytic enantioselective

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

For catalytic enantioselective Strecker reaction of ketoimines from other groups, see ... 

Groger H (2003) Catalytic enantioselective Strecker reactions and analogous syntheses. Chem Rev 103(8) 2795-2827... 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Corey and Grogan recently developed a novel catalytic enantioselective Strecker reaction which utilized the readily available chiral C2-symmetric guanidine 19 as a bifunc-tional catalyst [12], The addition of hydrogen cyanide to achiral aromatic and aliphatic N-benzhydrylimines 18 gave N-benzhydryl-a-aminonitriles 20 (Scheme 7), which were readily converted to the corresponding amino acids with 6 N HCI. The use of N-benzyl- or N-fluorenylimines afforded products of poor enantiomeric purity. 

H. Groeger, Catalytic Enantioselective Strecker Reactions and Analogous Syntheses, Chem. Rev. 2003, 103, 2795-2827. 

Kobayashi S, Ishitani H (2000) Novel binuclear chiral zirconium catalysts used in enantioselective strecker reactions. Chirality 12 540-543 Kobayashi S, Ishitani H, Nagayama S (1995) Synthesis 1995 1195 Kobayashi S, Ishitani H, Ueno M (1998) J Am Chem Soc 120 431 Kobayashi S, Kobayashi J, Ishitani H, Ueno M (2002) Catalytic enantioselective addition of propionate units to imines an efficient synthesis of anti-alpha-methyl-beta-amino acid derivatives. Chem Eur J 8 4185 1190 Krohn K, Kirst HA, Maag H (eds) (1993) Antibiotics and antiviral compounds. VCH, Weinheim... 

Masumoto S, Usuda H, Suzuki M, Kanai M, Shibasaki M (2003) Catalytic enantioselective Strecker reaction of ketoimines. J Am Chem Soc 125 5634-5635... 

Kato, N., Suzuki, M., Kanai, M., Shibasaki, M. Catalytic enantioselective Strecker reaction of ketimines using catalytic amount of TMSCN and stoichiometric amount of HCN. Tetrahedron Lett. 2004, 45, 3153-3155. 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

In the catalytic enantioselective Strecker reaction, chiral aluminium complexes, especially aluminium-salen-based catalysts and aluminium-binaphthol-based catalysts have been widely used, and great achievements have been obtained. In 2010, the Li group reported a highly enantioselective Strecker reaction of achiral IV-phosphonyl imines by using primary free L-phenglycine 42 as the catalyst and diethylaluminium cyanide as the nucleophile. This work also presented the novel use of nonvolatile and inexpensive diethylaluminium cyanide in asymmetric catalysis (Scheme 19.51). ... 

Table 13.26 Catalytic Enantioselective Strecker Reaction of Ke-toimines Using Gd/Ligand 7b Complex...

Nakamura andToru reported a catalytic enantioselective Strecker-type reaction to N-(2-pyridylsulfonyl)imines (42) in the presence of chiral bis(oxazoline)s-Mg(OTf)2 catalysts (Scheme 4.14) [14]. Product (43) was achieved in an enantiomeric excess of up to 84% ee and in quantitative yield at room temperature. The 2-pyridylsulfonyl group acts not only as a good activating moiety in the reaction with trimethylsilyl... 

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. 

More recently, a number of exciting advances in catalytic enantioselective versions of the Strecker reaction have been described [19, 28]. Lipton reported in 1996 that the cyclic guanidine dipeptide 141 promotes the asymmetric addition of HCN to imines with high yields and optical purities (Equation 19) [103]. The importance of the basic guanidine moiety was borne out by comparison of 141 with the histidine analogue 143, known to be effective for enantioselective cyanohydrin formation (see Chapter 2, Section 2.9) [104]. However, 143 failed to lead to high enantioinduction in the corresponding Strecker reactions [103]. 

Snapper and Hoveyda have investigated ligands that incorporate a Schiff base onto a peptide motif for enantioselective Strecker reactions of non-en-olizable substrates (Scheme 10.23) [111]. The synthetic utility of this transformation was elegantly highlighted in the catalytic enantioselective synthesis of the aromatic amino nitrile 155 (98%, 93 % ee) in the presence of titanium complexes of peptide ligand 154. This core subunit 155 was subsequently used in a total synthesis of the anti-HIV agent chloropeptin I (156) [112],... 

Jacobsen pioneered a number of chiral ureas and thioureas that function as chiral hydrogen-bond donors [40, 41], These were first showcased in enantioselective Strecker reactions in 1998 (see Chapter 10) [160]. The highly modular nature of these catalysts provided ready access to structural variants and facilitated the identification of thiourea 235 as an optimal catalyst in catalytic enantioselective Mannich reactions (Equation 20) [161]. Thus, a broad range of N-Boc-protected aromatic aldimines such as 233 afforded the corresponding products (cf 236) with excellent yield and enantioselectivity. 

A very efficient and universal method has been developed for the production of optically pue L- and D-amino adds. The prindple is based on the enantioselective hydrolysis of D,L-amino add amides. The stable D,L-amino add amides are effidently prepared under mild reaction conditions starting from simple raw materials (Figure A8.2). Thus reaction of an aldehyde with hydrogen cyanide in ammonia (Strecker reaction) gives rise to the formation of the amino nitrile. The aminonitrile is converted in a high yield to the D,L-amino add amide under alkaline conditions in the presence of a catalytic amount of acetone. The resolution step is accomplished with permeabilised whole cells of Pseudomonas putida ATCC 12633. A nearly 100% stereoselectivity in hydrolysing only the L-amino add amide is combined with a very broad substrate spedfidty. 

Scheme 6.43 Recycling study Polymer-bound Schiff-base thiourea 41 catalyzed the Strecker reaction of pivalaldimine without loss of activity or enantioselectivity even after 10 catalytic cycles.

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... 

Scheme 6.165 Enantioselective Strecker reactions catalyzed by biflinctional hydrogen-bonding guanidine organocatalyst 178. Catalytic action of 178 HCN hydrogen bonds to 178 and generates a guanidinium cyanide complex after protonation, which activates the aldimine through single hydrogen bonding and facilitates stereoselective cyanide attack and product formation.

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