Michael chiral cyclopentenes

On the other hand, Wang and co-workers [28, 29] made two important contributions to the synthesis of cyclopentene derivatives. Both reactions were initiated with a carbo-conjugated addition of malonates derivatives. The first one was a double Michael addition between enals and 7-malonate-a,(3-imsaturated esters catalyzed by XII rendering the final cyclopentanes with three stereogenic centers in good yields (87-92%) and excellent stereoselectivities (84—99% ee) [28]. As for the second one, Wang and co-workers focus on the synthesis of cyclopentenes. This reaction was based on a Michael-aldol sequence followed by dehydration, between aromatic enals and dimethyl 2-oxoethylmalonate [29]. A set of densely functionahzed chiral cyclopentenes were synthesized in high yields (63-89%) and excellent enantiose-lectivities (91-97% ee) (Scheme 10.13). 

Organocatalytic, enantioselective cascade Michael-aldol condensation catalyzed by readily available (5 )-diphenylprolinol triethylsilyl ether gives synthetically useful, highly functionalized chiral cyclopentenes (Scheme 6.12) [14],... 

Wang, J., Li, H., Xie, H., Zu, L., Shen, X., Wang, W. (2007). Organocatalytic enantioselective cascade Michael-aldol condensation reactions efficient assembly of densely function-aUzed chiral cyclopentenes. Angewandte Chemie International Edition, 46, 9050-9053. 

These problems could be minimized by the use of bulky and readily enolizable malonates and a sterically hindered organocatalyst such as 145. Accordingly, substrate 144, bearing a nucleophilic malonate and an electrophilic aldehyde group, was utilized for the cascade Michael-aldol condensation process (Scheme 1.54) [90]. The process is catalyzed efficiently by readily available (S)-diphenylprolinol triethylsilyl ether 145 to give synthetically useful, highly functionalized chiral cyclopentenes. 

Wang showed that two Michael reactions running in tandem fashion can afford highly functionalised cyclopentane derivatives (Scheme 8.26). Chiral tetrahydrothiophenes were synthesised in this way as well. In a similar way, cyclopentene derivatives were assembled by a Michael/aldol sequence if a diester-aldehyde was employed. ... 

Since the early example of a proline-catalyzed asymmetric domino Michael-aldol reaction reported by Bui and Barbas in 2000 [57], a number of these reactions have been successfully developed by several groups. For example, Wang et al. have reported the synthesis of chiral densely functionalized cyclopentenes on the basis of a domino Michael-aldol reaction followed by dehydration between aromatic enals and dimethyl 2-oxoethylmalonate [67]. High yields (63-89%) and enanhose-lectivities (91-97% ee) were obtained by using (S)-diphenylprolinol sUyl ethers as catalysts. On the other hand, the condensation of P-nitroketones 36 onto enals in the presence of 8 was shown by Hong et al. to afford the corresponding domino Michael-aldol products 37 through the iminium-enamine activation mode [68]. 

Inspired by the success of intramolecular addition and tautomerization of aldehydes with a pendant alkyne through cooperative catalysis of a secondary amine and an An complex, in 2008, Yang et al. reported a cascade reaction with the combination of a copper complex and an achiral secondary amine catalyst for the synthesis of attractive carbocycles [48]. This chemistry merged a pyrrolidine-promoted Michael addition via iminium ion intermediates and a Cu-catalyzed cycloisomerization protocol (Scheme 9.54). Various ketones and alkyne-tethered active methylene compounds could be converted into densely functionalized cyclopentene derivatives. Although the asymmetric version was not given, the chemistry described here was amenable for the implementation of asymmetric synthesis of such functionalized molecules by a combination of chiral amines and suitable Au complexes. 

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. 

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