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Organic Chemistry Highlights

Total Synthesis

Monday, January 4, 2021
Douglass F. Taber
University of Delaware

The Chen/Yang Synthesis of Pre-schisanartanin C

Isolated from Schisandra propinqua, an evergreen climbing shrub used in Chinese medicine, pre-schisanartanin C (3) offers a challenging 3-8-7 skeleton. Jia-Hua Chen and Zhen Yang of Peking University assembled 3 by way of the gold-catalyzed cyclization of 1 to 2 (J. Am. Chem. Soc. 2020, 142, 573. DOI: 10.1021/jacs.9b11872).

The iodide 9 was prepared via the Evans aldol reaction of 4 with 5. Reduction delivered 6, that was monoprotected with 7, then carried on to the stannane 8. Wittig-Still rearrangement set the geometry of the alkene, after which the product alcohol was converted to 9.

To promote the challenging enantioselective Diels-Alder cycloaddtion of 10 with 11 to give 12, the authors designed a new organocatalyst, combining the Jørgensen diaryl prolinol with an areneboronic acid to give the oxazaborolidine. Ring expansion of 12 to the cycloheptenone 13 was followed by conjugate reduction and trapping of the resulting enolate with 14, leading, after acylation, to the ester 15. Addition of the alkyl lithium reagent derived from 9, reduction and dehydration gave 16, that was oxidized and protected, completing the assembly of 1.

The gold-catalyzed cyclization of 1 to 2 proceeded via the carbene 17. The cyclization was best carried out by the addition of several portions of catalyst over several days.

The enol ester of 2 was converted to the enol ether, then the lactone was reduced and coupled with 18, leading to 19. Oxidation to the α-hydroxy ketone followed by equilibration gave 20, that was carried on to the alkenyl iodide 21. Coupling with 22 followed by Sharpless asymmetric dihydroxylation completed the synthesis of pre-schisanartanin C (3).

D. F. Taber, Org. Chem. Highlights 2021, January 4.