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Published on: June 13, 2022
Diastereoselective total synthesis of (±)-schindilactone a, Part 3: The final phase and completion
Wei-Wu Ren1, Zhi-Xing Chen, Qing Xiao
1Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Science and Peking-Tsinghua Center for Life Sciences at College of Chemistry of Peking University, Chengfu Road, 202, Beijing, 100871, China.
Abstract:
The final phase for the total synthesis of (±)-schindilactone A (1) is described herein. Two independent synthetic approaches were developed that featured Pd-thiourea-catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4. Other important steps that enabled the completion of the synthesis included: 1) A Ag-mediated ring-expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30; 2) a Pd-catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16; 3) a RCM reaction to generate oxabicyclononenol 10 from diene 11; 4) a cyclopentenone fragment in substrate 8 was constructed through a Co-thiourea-catalyzed Pauson-Khand reaction (PKR); 5) a Dieckmann-type condensation to successfully form the A ring of schindilactone A (1). The chemistry developed for the total synthesis of schindilactone A (1) will shed light on the synthesis of other family members of schindilactone A.
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