期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 140, 期 30, 页码 9652-9658出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.8b05549
关键词
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资金
- NIGMS [R01GM109054-01]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM109054] Funding Source: NIH RePORTER
To illustrate the synthetic significance of C-C activation methods, here we describe an efficient strategy for the enantioselective total syntheses of (-)-cycloclavine and (-)-S-epi-cycloclavine, which is enabled by an asymmetric Rh-catalyzed cut-and-sew transformation between benzocyclobutenones and olefins. Despite the compact structure of cycloclavine with five-fused rings, the total synthesis was accomplished in 10 steps with a 30% overall yield. Key features of the synthesis include (1) a Pd-catalyzed tandem C-N bond coupling/allylic alkylation sequence to construct the nitrogen-tethered benzocyclobutenone, (2) a highly enantioselective Rh-catalyzed carboacylation of alkenes to forge the indoline-fused tricyclic structure, and (3) a diastereoselective cyclopropanation for preparing the tetrasubstituted cyclopropane ring. Notably, an improved catalytic condition has been developed for the nitrogen-tethered cut-and-sew transformation, which uses a low catalyst loading and allows for a broad substrate scope with high enantioselectivity (94-99% e.e.). The C-C activation-based strategy employed here is anticipated to have further implications for syntheses of other natural products that contain complex fused or bridged rings.
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