Construction of Oxa‐Bridged Tetracyclic Frameworks through a Prins Bicyclic Annulation

Abstract

A wide array of aldehydes undergo smooth cross‐coupling with 5,6‐bis(2‐hydroxyethyl)‐2‐phenyl‐3a,4,7,7a‐tetrahydro‐1H‐isoindole‐1,3(2H)‐dione in the presence of 1.2 equiv. TMSOTf at –78 °C in dichloromethane to afford the corresponding hexahydro‐8a,4a‐(epoxyethano)pyrano[3,4‐f]isoindole‐1,3(2H,5H)‐dione derivatives in good yields with excellent diastereoselectivity. This is the first report on the stereoselective construction of oxa‐bridged tetracyclic frameworks through a bicyclization strategy.

Six-membered ring systems: with O and/or S atoms

“…When using (S)-glycidol instead of 2-alkyloxiranes, novel (1,3-epoxymethyl)isochromans are obtained (19OL8938). Tetrahydro-1H-4a,8a-(epoxyethano)isochromans are prepared in high yields and with excellent diastereoselectivity from 3-ene-1,6-diols and aromatic and aliphatic aldehydes through a Prins bicyclic annulation reaction (19EJO3567). Intramolecular FriedeleCrafts-type cyclization of 2-benzyloxy-3-bromo-N-tosylindolines mediated by Ag 2 O in nitromethane delivers mainly indolino[2,3-c]isochromans.…”