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Asymmetric Total Synthesis of Venezuelaene A via TEMPO+BF4--Mediated Oxidative Nazarov Cyclization and Cascade
Sujun Xie1, Axiao Tao1, Qian Wang1
1Department of Chemistry and Shenzhen Grubbs Institute and Guangming Advanced Research Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen518055, China.
Abstract:
The first and asymmetric total synthesis of venezuelaene A, a rare [5-5-6-7] tetracyclic diterpenoid featuring a highly strained trans-fused [5-5] bicyclic motif alongside a densely functionalized cyclopentane ring and six contiguous stereogenic centers, is reported. Our approach highlights (1) a TEMPO+BF4--mediated oxidative Nazarov cyclization that rapidly assembles the hydrindane core bearing the key C15-quaternary center; (2) a Stoltz decarboxylative allylic alkylation to highly diastereoselectively install the adjacent C3-quaternary center; (3) a strategic intramolecular carbon atom transfer that overcomes formidable challenges of both homologation and stereochemical control encountered with conventional approaches; and (4) an ene-yne-ene cascade metathesis that efficiently forges the [5-7] bicyclic system and ultimately the entire tetracyclic skeleton, representing the first example of constructing a highly strained trans-fused [5-5] bicyclic ring system via a metathesis reaction.
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