Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids
Xiaochen Tian1,2, Tengfei Xuan1,2, Jingkun Gao3
1Molecular Synthesis Center & Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.
Abstract:
Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products and pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis of tetrahydro-β-carboline skeletons have immense impacts and have attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition of 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types of chiral tetrahydro-β-carbolines bearing continuous multi-chiral centers and quaternary chiral centers. The method displays different endo/exo selectivity from traditional nitrone chemistry. The distinct power of this strategy has been illustrated by application to collective and enantiodivergent total syntheses of 40 tetrahydro-β-carboline-type indole alkaloid natural products with divergent stereochemistry and varied architectures.
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