Asymmetric [5+3] formal cycloadditions with cyclic enones through cascade dienamine-dienamine catalysis.
A few aminocatalytic modes, such as iminium ions and different dienamines, have provided versatile tools for the functionalization of cyclic enones at various sites. Described here is a previously unreported cascade dienamine/dienamine catalytic pathway for β-substituted 2-cyclopentenones, and even 2-cyclohexenone. It involves domino α'-regioselective Michael addition and a γ-regioselective Mannich reaction with 3-vinyl-1,2-benzoisothiazole-1,1-dioxides to give fused or bridged architectures, which incorporate a spirocyclic skeleton, in excellent stereocontrol, thus furnishing unusual [5+3] formal cycloaddition reactions. Moreover, preliminary biological assays showed that some of the chiral products exhibited promising activity against some cancer cell lines, thus indicating that such skeletons might serve as leads in drug discovery.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education, West China School of Pharmacy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041 (China).
Xiang
X
Yin
Yi
Y
Zheng
Xin
X
Feng
Kun
K
Jiang
Xue-Zhen
XZ
Wei
Ning
N
Gao
Ying-Chun
YC
Chen
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D013237:Stereoisomerism
D000588:Amines
cancer; cycloaddition; organocatalysis; regioselectivity; synthetic metehods