Spiro undecane-1.5.9-triones

Recently, a first example of an organocatalytic asymmetric domino Knoevenagel/ Diels-Alder reaction was reported by Barbas and coworkers (Scheme 2.182) [409]. Spiro[5,5]undecane-l,5,9-triones of type 2-818/2-819 were obtained from comma-daily available 4-substituted-3-butene-2-ones 2-813, aldehydes 2-814, and Mel-drum s acid (2-801) in the presence of 20 mol% of the amino acid 2-815 with 80-95% ee and diastereoselectivity of dr> 12 1. 

Tu and co-workers [189] described a series of new 3-pyrimidin-5-ylpropanamides 140, spiro[5.5] undecane-1,5,9-triones 141 and pyrimidin-5-ylpropanoic acids 142... 

SCHEME 2.23 Asymmetric synthesis of spiro[5,5]undecane-l,5,9-trione derivatives 87. 

D. B. Ramachary, N. S. Chowdari, C. F. Barhas IB, Angew. Chem. Int. Ed. Engl. 2003, 42, 4233 237. Organocatalytic asymmetric domino Knoevenagel/Diels-Alder reactions a hioorganic approach to the diastereospecific and enanti-oselective construction of highly suhstituted spiro[5,5] undecane-1,5,9-triones. 

D. B. Ramachary, Y. V. Reddy, A. Baneijee, S. Baneqee, Org. Biomol. Chem. 2011, 9, 7282-7286. Design, synthesis and biological evaluation of optically pure functionalized spiro[5,5]undecane-l,5,9-triones as HIV-1 inhibitors. 

C2iH2205f 7,11 Bis(5-methy1-2-fury1)spiro[5.5]undecane-1,5,9-trione, 45B, 352... 

On another occasion, Barbas s group developed the first organocatalytic diastereospecific and enantioselective direct asymmettic domino Knoevenagel/ Diels-Alder reactions that produce highly substituted spiro[5,5]undecane-l,5,9-triones 57 from commercially available 54, aldehydes 55, and 2,2-dimethyl-l,3-dioxane-4,6-dione 56 (Scheme 1.16) [18]. Among the catalysts screened, 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) proved to be the optimal catalyst with respect to yield, and provided 57 in 88% yield and 86% ee. Up to 93% yield and 99% ee were observed when the reaction was extended to other substrates. It is noteworthy that the product 57 was accompanied by a trace amount of the unexpected symmetric spirocyclic ketone 58. 

The asymmetric domino three-component Knoevenagel/Diels-Alder addition reaction promoted by the primary amine catalyst 9-amino-9-deoxy-epi-quinine was also reported. Various pharmacological multisubstituted spiro[5,5]undecane-1,5,9-triones were obtained in moderate to good yields (up to 81%) with excellent diastereo-(>99 1 dr) and enantioselectivities (up to 97% ee) [19]. The enamine-mediated Diels-Alder reactions of a,P-unsaturated ketones were also extended to nitroalkenes [20] and 3-olefmic oxindoles [21]. 

---