Strecker guanidine

The chiral guanidine s role as a strong Brpnsted base for the reactions of protic substrates has been proposed. In 1999, Corey developed a C -symmetric chiral guanidine catalyst to promote the asymmetric Strecker reaction [117]. The addition of HCN to imines was promoted high yields and high enantioselectivities for both electron-withdrawing and electron-donating aromatic imines (Scheme 64). 

Several years later, Corey disclosed the C2 symmetric bicyclic guanidine 19 as an effective bifunctional catalyst for the Strecker reaction (Scheme 5.40) [74]. According to the catalytic cycle, HCN should hydrogen bond to the catalyst to form guanidinium-cyanide complex A. A subsequent increase in acidity of the catalyst N—H proton allows donation of a hydrogen bond to the aldimine to form TS assembly B. Enantiofacial attack of CN to the bound aldimine gives the Strecker product. 

Scheme 6.164 Strecker reaction for examination of the catalytic efficiency of guanidine-functionalized diketopiperazine 177.

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. 

Guanidine was first obtained by Strecker in 1861 by the oxidation with hydrochloric acid and potassium chlorate of guanine (a substance found in guano and closely related to uric acid). 

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. 

Scheme 7. Asymmetric Strecker synthesis with chiral guanidine catalyst 19 (Corey and Grogan).

Corey and co-workers reported the use of a C2-symmetric guanidine catalyst (53) for the Strecker reactions of N-benzhydryl aldimines [65]. The catalyst is be-... 

Scheme 6.9 Guanidine-catalyzed Strecker reactions of aldimines.

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. 

While this catalyst could not be applied to the Strecker reaction, Lipton was able to modify this species and was the first to report an asymmetrically catalyzed Strecker reaction. He reasoned the imidazole did not possess sufficient basicity and prepared the corresponding guanidine derivative, cyclo[(5)-phenylalanyl-(5)-norarginyl] 56. 

NjOj mol wt 131.14. C 36.63%, H 6.92%. N 32.05%, O 24.40%. Present in muscular tissue of many vertebrates. Commercially isolated from meat extracts. Small amounts occur in the blood, but it is not found in normal urine from adults. The greater part of creatine in muscle is combined with phosphoric acid as phosphocreatine. Produced by liver and kidneys by the transfer of the guanidine moiety nf argi -nine to glycine which is then methylated to give creatine, lit vitro synthesis by liver and kidney tissues Borsook, Dub-noff. J. Biot Chem. 134, 635 (1940). Review and bibliography Peters, Van Slyke, Quantitative Clinical Chemistry Vol. I, Interpretations (Baltimore, 2nd ed., 1946). Synthesis by heating cyanamide with sarcosine Strecker, Jahresber. 

Strecker reaction to establish a new stereocenter is subject to asymmetric induction, capable of creating either a tertiary" or quaternary carbon atom in the presence of 59. The peptido-imine 60 proves to be an excellent ligand for the Ti(IV)-mediated cyanation of aldimines. On catalysis of the bicyclic guanidine 61 the addition of HCN to A-benzhydrylaldimines affords a-amino nitrile derivatives with moderate to good ee. ... 

A diketopiperazine 8 with an external guanidine function is proven to be an effective catalyst for the Strecker reaction of benzhydrylimine [14]. Corey s bicyclic guandine 20 [12b], which is the original of 12 (Scheme 4.12), also works well in the same reaction and the mode of action has been elucidated by density functional theory [63] (Scheme 4.22). 

A review elsewhere discusses catalytic Strecker reactions including guanidine catalysts [64]. 

Li, J., Jiang, W.-Y, Han, K.-L. et al. (2003) Density functional study on the mechanism of bicyclic guanidine-catalysed Strecker reaction. The Journal of Organic Chemistry, 68, 8786-8789. 

Inspired by the work of Inoue, Lipton and coworkers replaced the imidazole side chain of t icZo-peptide 50, which was efficient as catalyst in cyanohydrin synthesis from aldehydes (Scheme 13.29), with a more basic guanidine moiety in order to afford a catalyst capable of accelerating proton transfer in the Strecker reaction. The modified catalyst 52 was found to be effective in the synthesis of a-amino nitriles with very high yields from aromatic and aliphatic M-benzhydiyl imines, giving enantioselectivities of up to 99% (Scheme 13.30). ... 

Although numerous organocatalytic asymmetric Strecker reactions have been reported, guanidine-catalysed asymmetric Strecker reactions are scarce. The works of Lipton and Corey and their coworkers are amongst these rare reports. However, the validity of the former has been questioned by Kunz and coworkers, who found no enantioselectivity, when the reactions of Lipton and coworkers were repeated by them. ... 

Scheme 23.11 Guanidine-catalysed modified Strecker reaction reported by Corey and Grogan.

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