Formal Total Synthesis of and Cedrene by Preparation

Formal Total Synthesis of (+/-)-α- and βCedrene by Preparation of Cedrone. Construction of the Tricyclic Carbon Skeleton by the Use of a Highly Efficient Intramolecular Khand Annulation William J. Kerr, * Mark Mc. Laughlin, Angus J. Morrison, and Peter L. Pauson

William J. Kerr • University of Strathclyde – Glasgow U. K. • B. S. 1983 University of Strathclyde • Ph. D. 1986 University of Strathclyde – Peter Pauson and David Billington • NIH Postdoc – Brandeis University - MA – Myron Rosenblum • Postdoc – Imperial College – London – Steven Ley • 1989 – University of Strathclyde – 1991 – ICI Fine Chemicals Young Lecturer – 1997 Glaxo Welcome Prize for Innovative Organic Chem – 2002 Chair of Organic Chemistry – University of Strathclyde • Interests: Metal Mediated Synthetic Organic Chemistry

α- and β-Cedrene • Isolated in 1841 – Walter, P. Ann. Chem. 1841, 39, 247 – Juniperus cedrus and Juniperus thurifera • Characterized in 1953 – Stork, G. ; Breslow, R. J. Am. Chem. Soc. 1953, 75, 3291

Retrosynthesis • Key Step: Intramolecular Pauson Khand • Pauson Khand cyclization has been used in synthesis of other natural products. – Pentalenene, Hirsutene, Brefeldin A…etc

Forward Synthesis Scheme 1 • 2 nd Step: Originally - Saegusa Oxidation – Worked 92% yield • Not Catalytic – Used diallyl carbonate stoichiometric

Scheme 2 • Seyferth-Gilbert Homologation – Ohira-Bestmann reagent

Scheme 3 Pauson-Khand Cyclization

Scheme 4 • Mech of ketone deprotection

Final Steps Scheme 5.

Conclusion • Able to utilize the Pauson Khand cyclization – Formation of intermediate • Synthesis of target from simple starting material • Questions? ?