Chiral guanidine catalysts enantioselective reactions

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). 

Terada, M., Ube, H. and Yaguchi, Y. (2006) Axially chiral guanidine as enantioselective base catalyst for 1,4-addition reaction of 1,3-dicarbonyl compounds with conjugated nitroalkenes. Journal of the American Chemical Society, 128, 1454-1455. 

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... 

Surprisingly, there have been only few synthetic studies on polymer-supported asymmetric superbase reagents. Recently, Wannaporn and Ishikawa prepared a new chiral guanidine based polymer catalyst and applied it to the asymmetric Michael addition reaction of iminoacetate with methyl vinyl ketone [39] (Scheme 6.7). Although the catalyst shows only moderate levels of reactivity and enantioselectivity, the result demonstrates the possibility of expanding an exciting field of asymmetric synthesis using polymer-supported chiral superbase catalysts. 

More recently, Tan and co-workers reported the reaction of p,7-unsaturated thioesters with di-tert-butyl azodicarboxylate promoted by the chiral guanidine 32 as the Br0nsted base catalyst (Scheme 11.16) [57]. By judicious choice of the double bond geometry of the (3,y-unsaturated thioester compound, the reaction can deliver either enantiomeric product with excellent enantioselectivity. 

The first highly enantioselective reaction catalyzed by a chiral guanidine was reported by Corey and coworkers in 1999 [128], C2-symmetric guanidine 46 was shown to be a highly effective catalyst in the Strecker reaction of aromatic aldi-mines, affording the Strecker products in high yields and enantioselectivities (Scheme 10.43). 

Terada and coworkers reported, in 2010, an enantioselective, direct vinylogous aldol reaction of furanone derivatives with aromatic aldehydes catalyzed by axiaUy chiral guanidines (Scheme 10.49) [142]. Initial catalyst screening revealed that both the buUdness and the electronic nature of the G substituent on the guanidine had a large influence on catalytic activity as well as enantio- and diastereoselectivity. 

Tan et al. recently reported that chiral guanidine could be used as catalyst to catalyze the asymmetric Michael addition of malonate to 2-cyclopenten-l-one (Table 9.8). The results suggested that this chiral guanidine was exceptionally suitable for the asymmetric Michael addition of 2-cyclopenten-l-one and malonate. It should be noted that all malonates completely reacted with 2-cyclopenten-l-one to afford the Michael adducts with more than 90% of asymmetric induction. Moreover, basic additives such as achiral amines could greatly accelerate the rate of reaction. When triethylamine was used as the solvent, the reaction rate could be increased up to 1000 times without deteriorating the enantioselectivity. The asymmetric Michael additions of (3-keto ester to 2-cyclopenten-l-one were also investigated (Table 9.8). Excellent yields and enantio-selectivities were obtained within 72 hours. In particular, the asymmetric induction could be increased to more than 90% for ethyl 3-oxo-3-m-tolylpropanoate and ethyl 3-(4-nitrophenyl)-3-oxopropanoate when toluene was used instead of EtsN as the reaction medium. 

In addition to this highly enantioselective metal-catalyzed approach, several orga-nocatalytic versions of the asymmetric nitroaldol reaction have recently been reported. The Najera group used enantiomerically pure guanidines with and without C2 symmetry as chiral catalysts for the addition of nitromethane to aldehydes [126], When the reaction was conducted at room temperature yS-nitro alcohols of type 120 were obtained in yields of up to 85% but enantioselectivity, 26% ee or below, was low. A selected example is given in Scheme 6.52. Higher enantioselectivity, 54% ee, can be obtained at a low reaction temperature of —65 °C, but the yield (33%) is much lower. 

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. 

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. 

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