One-Pot Double Intramolecular Cyclization Approach to Tetralin-Based Cis-Fused Tetracyclic Compounds.

Abstract

Presented herein is a BF3·OEt2-mediated, diastereoselective one-pot double cyclization of 4-aryl-2-[(arylthio)methyl]butanals leading to the formation of cis-tetrahydro-6H-naphtho[2,1-c]thiochromenes for the first time. Mechanistically, the formation of the title products involves the one-pot intramolecular Friedel-Crafts hydroxyalkylation/intramolecular Friedel-Crafts alkylation cascade. This synthetic methodology is featured by its high atom economy, broad substrate scope, mild transition-metal-free reaction conditions, capability to assemble two new rings in one pot, and moderate to high yields (up to 94% yield). It was then applied in the synthesis of a thia analogue of brazilane and a chromeno[3,4-c]chromene derivative. Moreover, the methodology was successfully extended to the synthesis of cis-hexahydrobenzo[c]phenanthrenes. Specifically, 1,5-diarylpentan-3-ones were first subjected to the Corey-Chaykovsky reaction, and the resulting epoxides, without being chromatographically isolated, were treated with BF3·OEt2 to afford the cyclized products in high yields (up to 84% yield over two steps).