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Article

Applications of Zr-Catalyzed Carbomagnesation and Mo-Catalyzed Macrocyclic Ring Closing Metathesis in Asymmetric Synthesis. Enantioselective Total Synthesis of Sch 38516 (Fluvirucin B₁)

Supporting Info

Zhongmin Xu, Charles W. Johannes, Ahmad F. Houri, Daniel S. La, Derek A. Cogan, Gloria E. Hofilena, and Amir H. Hoveyda*

Contribution from the Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02167

J. Am. Chem. Soc., 1997, 119 (43), pp 10302–10316

DOI: 10.1021/ja972191k

Publication Date (Web): October 29, 1997

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

Abstract

The first enantioselective total synthesis of antifungal agent Sch 38516, also known as fluvirucin B₁, is described. The synthesis includes a convergent asymmetric preparation of amine 17 and acid 18, which are then united to afford diene 62. Metal-catalyzed transformations play a crucial role in the synthesis of the latter moiety. Of particular note are the diastereo- and enantioselective Zr-catalyzed alkylations, a tandem Ti- and Ni-catalyzed process that constitutes a hydrovinylation reaction, and a Ru-catalyzed alcohol oxidation to afford carboxylic acid 18. The requisite carbohydrate 38 is synthesized in a highly diastereo- and enantioselective fashion. Optical purity of the carbohydrate moiety arises from the use of the asymmetric dihydroxylation method of Sharpless; diastereochemical control is achieved through a selective dipolar [3 + 2] cycloaddition with a readily available amine serving as the chiral auxiliary. Union of the appropriately outfitted carbohydrate 71 and diene 62 through an efficient and diastereoselective glycosylation is followed by a remarkably efficient Mo-catalyzed macrocyclization that proceeds readily at room temperature.

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