Strecker reaction catalytic enantioselective

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. 

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... 

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.

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. 

The first enantioselective catalytic Strecker reaction of ketoimines to give chiral quaternary cyanohydrins was demonstrated by the Jacobsen group using 45b (Scheme 6.7) [41]. A series of substituted aryl and aliphatic N-benzyl methylketo-imines (48) reacted with HCN in the presence of 45b to provide essentially quantitative yields of the Strecker adducts in high optical purities (70-95% ee). The adducts were crystalline, and their recrystallization from hexanes increased their enantiopurities to >99.9% ee. The a-quaternary Strecker adducts (49) could be converted to a-quaternary a-amino acids through formamide protection of the secondary amine, followed by sequential hydrolysis of the nitrile and the formamide, followed by hydrogenolytic debenzylation. 

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

Job A, Janeck CF, Bettray W, Peters R, Enders D (2002) Tetrahedron 58 2253 Josephsohn NS, Kuntz KW, Snapper ML, Hoveyda AH (2001) Mechanism of enantioselective Ti-catalyzed Strecker reaction peptide-based metal complexes as bifunctional catalysts. J Am Chem Soc 123 11594—11599 Juhl K, Gathergood N, Jprgensen KA (2001) Catalytic asymmetric direct Man-nich reactions of carbonyl compounds with alpha-imino esters. Angew Chem Int Ed Engl 40 2995-2997... 

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... 

The enantioselective total synthesis of (-)-hemiasterlin, a marine tripeptide with cytotoxic and antimitotic activity, was achieved by E. Vedejs and co-workers. The asymmetric Strecker reaction was used to construct the key tetramethyltryptophan subunit. The aldehyde substrate was first converted to the corresponding chiral imine with (R)-2-phenylglycinol under scandium triflate catalysis. The addition of tributyltin cyanide resulted in the formation of a-amino nitriles as an 8 1 mixture of diastereomers. Subsequently the cyano group was converted to a primary amide, and the chiral auxiliary was removed under catalytic hydrogenation conditions. 

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. 

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