Synthesis of 3-benzylidene-dihydrofurochromen-2-ones: promising intermediates for biflavonoid synthesis

Abstract

A route to 3-benzylidene dihydrofurochromen-2-ones from 2H-chromenes is described. Lactonization of 2H-chromenes was achieved using a two-step cyclopropanation-rearrangement sequence. Subsequent conversion of these intermediates to the corresponding α-benzylidene lactones was achieved by lithium enolate Aldol reaction, followed by base-promoted elimination of the aldolate mesylates. The alkene geometry was found to be base-dependent. While KOtBu favored formation of the E-isomer, DBU showed a slight preference for the Z-isomer. In further studies, these 3-benzylidene dihydrofurochromen-2-ones were converted to polyaromatic structures possessing all the required functionality for biflavonoid synthesis.

Proceedings of Chemistry, Pharmacology, Pharmacokinetics and Synthesis of Biflavonoids

“…In 2015, Baron and Mead first synthesized 3-benzylidene-dihydrofurochromen2-ones (S14), a flavan-chalcone type biflavonoid [ 336 ]. This was the first time de novo synthesis was attempted.…”