A Second-Generation Synthesis of the Cyanthiwigin Natural Product Core
An improved synthesis of the cyanthiwigin natural product core enabled by new catalytic technology is reported. The key double catalytic enantioselective alkylation has been reoptimized using a recently developed protocol employing low loadings of palladium catalyst, thereby facilitating large-scale production of the tricyclic cyanthiwigin framework. Additionally, preparation of the penultimate aldehyde intermediate is expedited through the application of anti-Markovnikov Tsuji–Wacker oxidation.
Additional Information© 2016 American Chemical Society. Received: September 30, 2016. Publication Date (Web): October 20, 2016. This work was supported by the NSF under the CCI Center for Selective C–H Functionalization (CHE-1205646). Additional financial support was provided by Caltech and Novartis. Dr. Scott C. Virgil (Caltech), Dr. John A. Enquist, Jr. (Gilead), and Dr. Grant M. Shibuya (SiteOne Therapeutics) are acknowledged for helpful discussions. The authors declare no competing financial interest.
Supplemental Material - ol6b02962_si_001.pdf