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Synlett 2009(9): 1357-1366  
DOI: 10.1055/s-0028-1216728
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Efforts Towards the Synthesis of the Complex Diterpene Providencin

Tanja Gaich, Harald Weinstabl, Johann Mulzer*
Institute of Organic Chemistry, University of Vienna, Währinger Str. 38, 1090 Vienna, Austria
Fax: +43(1)427752189; e-Mail: johann.mulzer@univie.ac.at;
Further Information

Publication History

Received 6 August 2008
Publication Date:
17 April 2009 (online)

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Abstract

Providencin is a novel, highly oxygenated marine furanocembranolide featuring a cyclobutane ring and a highly strained 7,8-trans-epoxide. Various approaches to the total synthesis of this compound are reported. The cyclobutane moiety is generated via [2+2] cycloaddition and the furan ring is constructed via a Wipf ­palladium-catalyzed alkynone cyclization. The macrocyclic ring is closed via a Horner-Wadsworth-Emmons olefination or ring-­closing metathesis. The latter reaction, however, produces the undesired 7,8-Z-olefin exclusively, and the conversion into the E-isomer has been, thus far, unsuccessful.

1 Introduction

2 Retrosynthetic Analysis

3 First Generation Approach

3.1 Synthesis of the Cyclobutane Moiety

3.2 Synthesis of the Western Fragment

3.3 Combination of Both Fragments and Ring Closure via
Horner-Wadsworth-Emmons Olefination

4 Second Generation Approach via Ring-Closing Metathesis

5 Cyclobutane Model Studies

6 Conclusion

Key words

furanocembranolides - total synthesis - macrocycles, Horner-­Wadsworth-Emmons olefination - ring-closing metathesis