Total Synthesis of Confertin via Metal-Promoted Cyclization-Lactonization

1. Total Synthesis of Confertin via Metal-Promoted Cyclization-Lactonization M.F. Semmelhack*, A. Yamashita, J.C. Tomesch, K. Hirotsu J. Am. Chem. Soc. 1978, 100, 5565 Presented by: Steven Rossi May 15, 2012

2. Martin F. Semmelhack • Born: November 19, 1941 (Appleton, Wisconsin) • University of Wisconsin (1963) • Ph.D. Harvard (1967), E.J. Corey • Postdoc: Stanford, William S. Johnson • 1968: Assistant Professor at Cornell University • Cornell: 1973, Associate Professor. 1977, Professor • 1978-Present: Princeton University • Served on the Executive Committee for the Organic Division of ACS, and was the chair (1988) • Editorial Board for J. Org. Chem., Organometallics, • 150+ publications • Recipient of the Camille and Henry Dreyfuss Fellowship, Alfred P. Sloan Foundation fellowship, Guggenheim Fellowship

3. Confertin • First isolated from Ambrosia confertiflora in 1968 • Recentyl isolate from Ambrosia Tenuifolia • Midwest-West Coast of U.S. • Confertin classified as a member of the pseudoguaianolide family under sesquiterpenes • Has shown cytotoxicity and antitumor activity

4. Confertin

5. Total Synthesis • R.H. Ellison: J. Am. Chem. Soc. 1976, 98, 4312. • P.A. Wender: J. Am. Chem. Soc. 1979, 101, 2196. • G. Quinkert: Angew. Chem. Int. Ed. 1987, 26, 61. • T. McKervev: Perkin Trans. I. 1991, 2565. • K. Shishido: Tett. Lett. 1998, 39, 5803. …to name a few

6. Retrosynthesis

7. Starting Material Boeckman, R. Blum, D.M. J. Org. Chem. 1974, 39, 3307.

8. Forward Synthesis

9. Forward Synthesis

10. Nickel-Promoted Cyclization-Lactonization

11. Final Steps

12. Conclusions • 15 Step Synthesis • Major Step: Nickel-Promoted Cyclization-Lactonization • More recent synthesis are stereoselective Questions?