Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids.

Tian, Xiaochen; Xuan, Tengfei; Gao, Jingkun; Zhang, Xinyu; Liu, Tao; Luo, Fengbiao; Pang, Ruochen; Shao, Pengcheng et al. · Nat Commun · 2024

basic_science · Level V

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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.