Enantioselectivity Strecker reaction

A new cinchona alkaloid-derived catalyst has been developed for the enantioselective Strecker reaction of aryl aldimines via hydrogen-bonding activation. For reference, see Huang, J. Corey, E. J. Org. Lett. 2004, 6, 5027-5029. 

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 6.165 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.

Reagent 8 has also been used to add guanidine groups to a supported dipeptide intermediate to a diketopiperazine4 1 that is reported to be a catalyst for enantioselective Strecker reactions.44 The key step is shown in Scheme 19. 

An enantioselective Strecker reaction involving Brpnsted acid catalysis uses a BINOL-phosphoric acid, which affords ees up to 93% in hydrocyanations of aromatic aldimines in toluene at -40 °C.67 The asymmetric induction processes in the stereoselective synthesis of both optically active cis- and trans-l-amino-2-hydroxycyclohexane-l -carboxylic acids via a Strecker reaction have been investigated.68 A 2-pyridylsulfonyl group has been used as a novel stereocontroller in a Strecker-type process ees up to 94% are suggested to arise from the ability of a chiral Lewis acid to coordinate to one of the sulfonyl (g)... 

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. 

Chiral diketopiperazines in enantioselective Strecker reactions 03CRV2795. 

For theoretical studies on enantioselective Strecker reaction catalyzed by chiral phosphoric acids, see Simon. L. and Goodman, J.M. (2009) J. Am. Chem. Soc.,... 

Corey and Grogan reported an enantioselective Strecker reaction via the C2-symmetric guanidine 14 (Equation 10.28) [56]. They proposed the transition-state structure shown in Figure 10.14, where the imine is activated by hydrogen bonding. 

Bridged trimethylene and tetramethylene 2,2 -quinoline di-N-oxides of 37 were revisited by Jiang et al. The enantiomers were obtained through resolution of the racemates with optically pure dibenzoyltartaric acid. The absolute configuration of the trimethylene enantiomers was determined by X-ray analysis on the resulting diastereomeric complex. The enantiomers were assayed as chiral promotors in the enantioselective Strecker reaction between benzaldehyde N-benzhydrylimine and HCN (01SL1551, 03EJOC3818). 

The alkali-metal-salt-catalyzed enantioselective Strecker reaction of ketimines (176) with TMSCN has been developed by employing chiral (5)-BNPNa (177) (BNP = 1,1 -binaphthyl- 2,2 -diylphosphate) and PBAP (/ -t-butyl-6>-adamantylphenol) (Scheme 48). The simplicity and facile availability of the catalyst and high enantioselectivities of the reaction made it potentially applicable in synthesis. 

Highly enantioselective Strecker reaction of aldimines (614) and keti-mines with ethyl cyanoformate as a cyanide source in the presence of Al-catalyst (616) to give (615) has been reported by Yamamoto and Abell (Scheme 154). °... 

One of the most interesting developments in the field of stereoselective synthesis of amino acids is unquestionably the enantioselective Strecker reaction. Being a fairly recent discovery, the reaction has not yet been advanced to the industrial... 

Eric Jacobsen s first catalyst for the enantioselective Strecker reaction was an aluminium-salen complex (Tab. 4.2). [92]... 

The enantioselective Strecker reaction also succeeds with ketoimines. Thus, a-hranched amino-nitriles [94] and also unnatural amino acids [95] can he obtained hy this method. The precise mechanism of the catalysis is unclear. Kinetic investigations have previously shown, that the turnover reflects a Michaelis-Menton relationship. The imine is bonded reversibly to the catalyst. The addition of hydrogen cyanide is rate-determining. [96]... 

Scheme 9.8 Enantioselective Strecker reaction using chiral vanadium(v) complex 2, reported Ity Crampton and North.

Scheme 19.3 First asymmetric thio(urea) catalyst. Enantioselective Strecker reaction.

Zirconium(rV) t-butoxide, Zr(OtBu)4 is a widely used component of various in situ catalysts. BINOL, its 3,3 -dibromo and 6,6 -dibromo derivatives, and TAD-DOL have been used as chiral ligands (138). These types of catalysts have been used for enantioselective Strecker reactions and Mannich-type reactions (139). 

Various oxazoline-based organocatalysts were prepared and applied to enantioselective Strecker reactions of different N-benzhydrylimines with TMSCN. In particular, derivative 156 allowed the synthesis a-amino nitriles in high yield and with excellent chiral induction (13CEJ14224). 

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