Molecular Acrobatics in Polycyclic Frames: Synthesis of “Kurmanediol” via Post-synthetic Modification of Cage Molecules by Olefinic Metathesis

Abstract

We report late-stage ring-opening metathesis (ROM), ring-rearrangement metathesis (RRM), and ring-closing metathesis (RCM) approaches to generate expanded pentacycloundecane (PCUD) cage derivatives. These higher-order intricate polycyclic cage systems are aesthetically pleasing and structurally intriguing. Their assembly maintains molecular symmetry during the entire synthetic sequence. To this end, metathesis-based catalysts are used to execute the ROM, RRM, and RCM strategies. The synthetic approach to these cage polycycles involves the Diels−Alder reaction, [2 + 2] photocycloaddition, RRM, ROM, and RCM as key steps.

Synthetic Approach toward Diverse Oxa-Cages via Olefin Metathesis

“…22a However, the ring-opening of the modified cage scaffolds 21 and 22 under various metathesis conditions was not realized. 23 Thus, the reduced ring strain and increased steric congestion are useful for designing new substrates suitable for regioselective RCM products. In this regard, the modified cage dione 21 was treated with allyl bromide and sodium hydride in dry THF at rt, which gave 23 in 90% yields (Scheme 4).…”

“…(2a 1 R,4aS,5S,9R,9aS)-4a,9-Diallyl-1,2,2a,2a 1 ,3,4a,5,8,9,9a-decahydro-4H-1,3,9-(epiethane[1,1,2]triyl)-5,8-methanocycloocta[cd]pentalene-4,10-dione (23).…”

“…As indicated by the earlier result, ROM of the diastereomeric pairs ( 12 and 13 ) occurs readily with either G-I or G-II under mild reaction conditions . However, the ring-opening of the modified cage scaffolds 21 and 22 under various metathesis conditions was not realized . Thus, the reduced ring strain and increased steric congestion are useful for designing new substrates suitable for regioselective RCM products.…”

Annulations involving p-benzoquinones: stereoselective synthesis of fused, spiro and bridged molecules

“…Finally, we discuss the synthesis of an interesting cage molecule, namely, “Kurmanediol” as reported by Kotha and Mehta. 112 When cyclopentadiene 147 was reacted with benzoquinone derivative 146 in benzene, the corresponding Diels–Alder cycloadducts 148a / 148b were obtained in 60% yield (Scheme 42). Subsequently, the diastereomeric mixture of 148a / 148b was irradiated with a 125 W UV lamp to achieve heptacyclic cage dione diastereomers 149a / 149b , which could be separated via the time-consuming column chromatography.…”