Approach to a New Dihydrofuran-Fused Cyclic System by a Remarkable Switching of endo/exo Selectivity of a [4+2] Cyclo­addition Reaction

• Published in: European Journal of Organic Chemistry 2008, Vol.2008 (8), p.1426-1430
• Main Authors: Matsuya, Yuji, Imamura, Yoshiaki, Miyahara, Tatsuro, Ochiai, Hiroshi, Nemoto, Hideo
• Format: Review
• Language: English
• Subjects: Anti-influenza agent; Cycloaddition; Diastereo­selectivity; Pericyclic reaction; Quinodimethanes
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200701050

An efficient synthesis of a new class of dihydrofuran‐fused tetracyclic compounds, possessing a 2‐oxa‐furano‐steroidal framework, has been achieved by successive electrocyclic reactions of benzocyclobutene derivatives. It has been revealed that the stereoselectivity of a key intramolecular [4+2] cycloaddition reaction can be controlled by installation of a bulky silyl substituent onto the furan ring resulting in the formation of the exo adducts, the opposite selectivity to that observed in our past related studies. Preliminary examinations of the bioactivities of the synthesized compounds have been performed and have revealed that they have potential as anti‐influenza agents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) A new class of furan‐fused tetracycliccompounds, which have an oxa‐furano‐steroidal framework, have been synthesized via an o‐quinodimethane generated by thermal electrocyclic ring‐opening of benzocyclobutene derivatives. The stereoselectivity could be controlled by preinstallation of a bulky silyl substituent onto the furan ring, enforcing an exo transition state. Preliminary biological evaluation of these compounds suggests they have potential as new anti‐influenza agents.