Cycloisomerization of Conjugated Trienones and Isomeric 2H-Pyrans: Unified Strategy toward Cyclopenta[b]furans

Abstract

Conjugated trienones and isomeric 2H-pyrans were found to engage in a novel cycloisomerization cascade toward cyclopenta[b]furan derivatives. Knoevenagel chemistry and pericyclic reactions meet again to expand the polyene-carbonyl manifold.

The iso-Nazarov reaction

“…69 Since we later found that the process could be rendered possible also under neutral conditions (refluxing toluene) we departed from the classical cationic point of view and a pericyclic cascade was elaborated and supported computationally. 75 This proposal involves an initial isomerization via well-known oxa-6π processes to deliver a We were somehow pretty sure that, based on the ease with which these polyenes undergo neat and precise polycylizations, this cascade had to be traced in Nature. In this context, we proposed that citridone A (178), a furopyridone belonging to a new family of natural products recently presented by Nobel Laureate S.…”

Biomimetic Domino Knoevenagel/Cycloisomerization Strategy for the Synthesis of Citridone A and Derivatives

“…Putative polyunsaturated intermediate 9 , obtained via Knoevenagel condensation using the ethylenediammonium diacetate (EDDA) catalyst, undergoes spontaneous rearrangement into its polycyclic cyclopenta­[ b ]­furan isomer 10 . Both ionic and pericyclic pathways were proposed to account for the formation of 10 , the former featuring a Nazarov-type 4πe – -cyclization and the latter a [ π 4 a + π 4 s ] intramolecular cycloaddition (Scheme A, paths a and b, respectively). , The use of pyridone-type dicarbonyl substrates in this sequence may provide straightforward access to 1 and non-natural analogues. However, the condensation of these types of nucleophilic compounds seems more challenging.…”

“…2 H -Pyrans such as 14 and 15 are the result of well-known formal [3 + 3] cycloadditions that would comprise a domino Knoevenagel/oxa-6π electrocyclic ring-closure sequence taking place upon suitable combination of a dicarbonyl substrate and unsaturated aldehyde . Due to the emergent importance of the cyclopenta­[ b ]­furopyridone motif and taking into account the sensitivity of 2 H -pyrans to ring-opening processes, we became intrigued by the possibility of attaining such a desired reaction. Herein, we report our studies on a one-pot domino Knoevenagel/bicyclization strategy for the synthesis of citridone A and analogues (cyclopeta­[ b ]­furopyridones/quinolones 16 ), which we hope will promote further studies on this novel class of alkaloids (Scheme D).…”

Total Synthesis of (+)-Granatumine A and Related Bislactone Limonoid Alkaloids via a Pyran to Pyridine Interconversion

“…With a scalable route to 8 and 9 , the convergent fragment coupling through a Knoevenagel condensation was investigated (Scheme A). Treatment of 8 and aldehyde 9 with ethylenediammonium diacetate (EDDA) , formed presumed enedione intermediate 23 , which under thermal conditions spontaneously underwent an oxa-6π electrocyclization to give 2 H -pyran 7 as the only product on a gram scale in 47% yield from 9 . The oxa-6π electrocyclization allowed for a regioselective C1 ketone protection in the presence of the C3 ketone…”