Catalysts bicyclic guanidine

Figure 13.9 Some bicyclic guanidine catalyst scaffolds.

Corey, E. J. Grogan, M. J. Enantioselective Synthesis of a-Amino Nitriles from N-Benzhydryl Imines and HCN with a Chiral Bicyclic Guanidine as Catalyst Org Lett. 1999,1,157-160. 

In 2006, Tan and co-workers reported the first asymmetric guanidine catalyzed Diels-Alder addition of anthrone to maleimides (Scheme 75) [130], The authors observed very high yields and enantioselectivities using a derivative of Corey s C2-symmetric bicyclic gnanidine catalyst. The addition of anthrones to maleimide also worked well for snbstitnted anthrones. Interestingly, the anthors observed the oxidized prodnct when the anthrone was substituted at the meto-positions (Scheme 76). 

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. 

Chiral bicyclic guanidine (221) has been identified as an excellent catalyst for reactions between anthrones (219) and various dienophiles, such as (220). The catalyst can tolerate a range of substituents and substitution patterns, making several anthrone derivatives suitable for this reaction. Both Diels-Alder and Michael adducts were obtained in excellent yields, high regioselectivities, and high enantioselectivities (<99% ee). This is the first case of a highly enantioselective base-catalysed anthrone Diels-Alder reaction.263... 

Corey EJ, Grogan MJ (1999) Enantioselective synthesis of alpha-amino nitriles from N-benzhydryl imines and HCN with a chiral bicyclic guanidine as catalyst. Org Lett 1 157-160... 

Asymmetric nitro-Michael reactions of methyl vinyl ketone (MVK) in the presence of bicyclic guanidine with a benzhydryl group led, disappointedly, to low asymmetric induction (9-12%) [21a] Trials for the reaction of 0 ,p-unsaturated y- or 8-lactones with pyrrolidine in the presence of the conjugate acids of a bicyclic guanidine [50] or the Murphy s guanidine [24a] (R = Me in Scheme 4.7) resulted in the production of racemic compounds. The latter phase transfer catalyst (PTC) catalyses the nitro-Michael addition of chalcone but with limited range (70% yield, 23% ee) [24c]. 

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). 

Davis, A.P. and Dempsey, K.J. (1995) Synthesis and investigation of a hindered, chiral, bicylic guanidine. Tetrahedron Asymmetry, 6, 2829-2840 Corey, E.J. and Grogan, M.J. (1999) Enantioselective s)mthesis of a-amino nitriles from A-henzhydry 1 imines and HCN with a chiral bicyclic guanidine as catalyst. Organic Letters, 1, 157-160. 

Ye, W., Jiang, Z., Zhao, Y. et a/. (2007) Chiral bicyclic guanidine as a versatile Brdnsted base catalyst for the enantioselective Michael reactions of dithiomalonates and P-keto thioesters. Advanced Synthesis and Catalysis, 349, 2454-2458. 

Guanidines have also been employed as catalysts in Michael reactions with enones and, for example, bicyclic guanidine 86 has been found to perform well in the Michael reaction of different 1,3-dicarbonyl compounds with cyclo-pentenones, providing the final Michael adducts with excellent yields and enantioselectivities (Scheme 4.33). In this case, the authors found that the use of triethylamine as solvent resulted in a dramatic increase in the rate of the reaction, without affecting significantly its stereochemical outcome with respect to the same reaction in toluene, which is the usually chosen solvent when working with this type of catalyst. 

EUas J. Corey used a bicyclic, enantiomerically pure guanidine as catalyst, and in the case of benzaldehyde, he achieved an enantiomeric excess of 86 %. Crucial to the enantioselectivity are the van der Waals forces and the n-stacking interactions between unine and catalyst. [91 ]... 

Based on the cumulative E-factors tabulated in Table 23.3, Feng-G has the lowest cumulative E-factor of 60. Synthesis of the bicyclic guanidines Tan-G and Corey-G suffers from the most unfavourable E-factor of >330 i.e. 1 g of catalyst generates 484 g of waste in the case of Corey-G). While Corey and Grogan have demonstrated that the catalyst could be recycled through the... 

In addition, several organocatalysts other than cinchona alkaloid derivatives have been developed very recently. As an example, a chiral bicyclic guanidine was found by Tan et al. to be an excellent catalyst for enantioselective Michael additions of malonates or ethyl benzoylacetates to cyclopentenone or... 

The chiral bicyclic guanidine 170 acts as a Bronsted base catalyst. The hydroxy group controls diastereo- and enantioselectivities in the direct aldol reaction of 5H-oxazol-4-ones (169) with aldehydes (62). The aldol products (171) are easily converted into amides or esters without loss of enantiopurity thus, this method provides synthetically usefiil a,p-dihydroxycarboxylates bearing a chiral quaternary stereogenic center at the a-carbon atom (Scheme 28.18) [88]. 

Scheme 30.2 Application of a C2-symmetrical bicyclic guanidine as catalyst.

More recently, Tan and coworkers successfully broadened the substrate scope and improved the enantioselectivihes for the Diels-Alder reactions of anthrones by utilizing new chiral bicyclic guanidine 84 as catalyst (Figure 38.3) [35]. Notably,... 

The mechanism and origin of enantioselectivity has been evaluated for a bicyclic guanidine-catalyzed phospha-Michael reaction between diphenyl-phosphine oxide and p-nitrostyrene by DFT calculations (Scheme 32). The catalyst was found to be involved in all three steps of the catalytic cycle proposed. 

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