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Organic Chemistry Highlights

Monday, December 18, 2023
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: δ-Cadinol (Schulz), KB343 (Baran), Penostatin C (Chen), Senopodine E (Ishikawa), Vermisporin (Lei), Kibdelomycin (Schobert)

Stefan Schulz of the Technische Universitšt Braunschweig updated the classic intramolecular Diels-Alder cycloaddition of the triene 1 to the ketone 2, readily convertible to δ-cadinol (3), by preparing 1 via an enantioselective Michael addition, and carrying it on to 2 via cascade enone formation/cyclization. δ-Cadinol (3) is also known as torreyol, sesquigoyol, albicaulol and pilgerol (Beilstein J. Org. Chem. 2023, 19, 167. DOI: 10.3762/bjoc.19.16).

The pentacyclic guanidinium alklaloid KB343 (7) was isolated off the coast of Palau from the tunicate Epizoanthus illoricatus. Phil S. Baran assembled 7 by way of the enantioselective Co-catalyzed cycloaddition of the unsaturated aldehyde 5 with Rawal's diene 4 to give 6 (J. Am. Chem. Soc. 2023, 145, 7753. DOI: 10.1021/jacs.3c01991).

Methyl cyclopentadiene 9 is an equilibrating mixture of three regioisomers. Nevertheless, Xiaochuan Chen of Sichuan University showed that cycloaddition with the enone 8 proceeded via the most reactive of the three, leading to the ketone 10, that they carried on to penostatin C (11) (Org. Lett. 2023, 25, 1941. DOI: 10.1021/acs.orglett.3c00485).

The aldehyde 13 is not a very reactive Diels-Alder diene. Hayato Ishikawa of Chiba University showed that in the presence of benzoic acid, 13 was in equilibrium with the corresponding β-,γ-isomer, which engaged with the dienophile 12 to give 14, the carbocyclic portion of senopodine E (15) (Org. Lett. 2023, 25, 1151. DOI: 10.1021/acs.orglett.3c00133).

As Xiaoguang Lei of Peking University anticipated, Diels-Alder cyclization of the Z-enone 16, although reluctant, could be accelerated with Lewis acid, proceeding via an ordered boat transition state to give the cis-fused ketone 17. This was carried on to the antibiotic vermisporin (18), originally isolated from the fungus Ophiobolus vermisporus L-8 (Angew. Chem. Int. Ed. 2023, 62, e202301872. DOI: 10.1002/anie.202301872).

The triene 19 was prepared by Rainer Schobert as an inconsequential mixture of epimers. The diastereoselective Diels-Alder cyclization of the E-enone to 20 was facile, setting the stage for the preparation of a known advanced intermediate in the synthesis of the antibiotic kibdelomycin (21) (Chem. Sci. 2023, 14, 3562. DOI: 10.1039/D3SC00595J).

D. F. Taber, Org. Chem. Highlights 2023, December 18.
URL: https://www.organic-chemistry.org/Highlights/2023/18December.shtm