A New Preparative Route to Substituted Dibenzofurans by Benzannulation Reaction. An Application to the Synthesis of Cannabifuran

Abstract

A N e w R o u t e t o S u b s t i t u t e d D i b e n z o f u r a n s Abstract: A new regioselective pathway to substituted dibenzofuran derivatives is described here. According to this procedure substituted 1-acetoxy-3-alkoxycarbonyl dibenzofurans are obtained by treatment of 6-(2-methoxyaryl)-3-alkoxycarbonylhex-3-en-5-ynoic acids with acetic anhydride in the presence of sodium acetate. The latter acids are prepared from the easily available substituted o-iodo-anisoles by Sonogashira coupling with propargylic alcohol and Wittig reaction as the key steps. The described benzannulation reaction proceeds in regioselective fashion and a range of substituents are tolerated. Its synthetic utility is demonstrated by a new synthesis of cannabifuran, a naturally occurring dibenzofuran.

Total synthesis of the aglycone of IB-00208

“…When the cyclobutenol 23 was heated, a simple Moore rearrangement occurred to give 24 . 10,11 The putative acetylenic vinyl ketene intermediate did not undergo the desired cyclization as expected from the work of Fuganti 15 under any of the conditions examined.…”

“…15,16 The newly formed furan and benzene rings were suggested to have been formed in a single annulation step via the ketene intermediate 11 .…”

Syntheses, spectroscopic and crystallographic characterizations of 4-nitrobenzyloxy derivatives and benzofurans from ortho-substituted benzaldehydes and 4-nitrobenzyl bromide

“…Consequently, there has been growing interest in developing general and versatile synthetic methods for benzofuran derivatives [18][19][20]. Recently, the synthetic methods for the construction of benzofurans mainly are dehydrative cyclization of a-(phenoxy)-alkyl ketones [21], decarboxylation of o-acylphenoxyacetic acids or esters [22], phosphazene base catalyzed intramolecular cyclization for efficient synthesis of benzofurans [23], one-pot synthesis under microwave irradiation and solvent-free conditions [24], etc.…”

Approaches to Polycyclic 1,4-Dioxygenated Xanthones. Application to Total Synthesis of the Aglycone of IB-00208

“…In our original plan, we had envisioned that electrocyclic ring opening of 7 would generate the acetylenic vinyl ketene 6 in accord with the findings of Moore . Simple analogs of 6 can cyclize via a radical pathway, a reaction manifold that our group leveraged in a concise total synthesis of cribrostatin 6, but compound 6 is also suitably substituted to undergo cyclization via an ionic pathway to give 5 in a process inspired by a related transformation reported by Fuganti . Intermediate 7 would be accessed by union of the aldehyde 8 and the key intermediate fused-cyclobutenone 9 by an acetylide stitching sequence.…”

“… 9 Simple analogs of 6 can cyclize via a radical pathway, a reaction manifold that our group leveraged in a concise total synthesis of cribrostatin 6, 11 but compound 6 is also suitably substituted to undergo cyclization via an ionic pathway to give 5 in a process inspired by a related transformation reported by Fuganti. 12 Intermediate 7 would be accessed by union of the aldehyde 8 and the key intermediate fused-cyclobutenone 9 by an acetylide stitching sequence. When we initiated this project, angular, polycyclic cyclobutenedione derivatives such as 9 were unknown, but we reasoned 9 might be accessible from coupling of 10 and the known vinyl squarate 11 , 13 followed by ring closing metathesis (RCM) to form the benzene ring in 9 .…”