Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 28, 2017
Douglass F. Taber
University of Delaware

Other Methods for Carbocyclic Construction: Nigramide R (Donohoe), Aplydactone (Trauner), Huperzine A (White), Podophyllotoxin (Czarnocki), Strophasterol A (Heretsch), Jungermannenone B (Lei)

Nigramide R (3), apparently racemic, was isolated from Piper nigrum. To construct 3, Timothy J. Donohoe of the University of Oxford dimerized (Angew. Chem. Int. Ed. 2016, 55, 4748. DOI: 10.1002/anie.201511683) 1 to 2 with high diastereocontrol.

The fused double cyclobutane natural product aplydactone 6 was isolated from the sea hare Aplysia dactylomela. Dirk Trauner of the Ludwig-Maximilian-Universität München assembled (Angew. Chem. Int. Ed. 2016, 55, 11251. DOI: 10.1002/anie.201604102) the core of 6 by the diastereoselective intramolecular photocyclization of 4 followed by diazo transfer and Wolff rearrangement to the ester 5.

James D. White of Oregon State University also employed (J. Org. Chem. 2015, 80, 11806. DOI: 10.1021/acs.joc.5b01619) intramolecular photocyclization to prepare the ketone 7. In this case, however, the object was to set the stage for the aza-Prins rearrangement of the cyclobutane 8 to huperzine A (9).

En route to podophyllotoxin (12), Zbigniew Czarnocki of the University of Warsaw used (Org. Biomol. Chem. 2016, 14, 460. DOI: 10.1039/C5OB01844G) photolysis to cyclize 10. The reaction was carried out in a simple flow apparatus, and the initial cyclization product was quenched directly into acidic methanol to convert it to the more stable 11.

Radical cyclizations usually proceed with a preference for the cis product. Nevertheless, Philipp Heretsch of the Freie Universität Berlin assembled (Angew Chem. Int. Ed. 2016, 55, 11656. DOI: 10.1002/anie.201605752) strophasterol A (15) by the reductive cyclization of 13 to 14.

Xiaoguang Lei of Peking University showed (Angew. Chem. Int. Ed. 2016, 55, 3112. DOI: 10.1002/anie.201511659) that reductive cyclization of 16 with the sterically demanding tributyltin hydride led exclusively to 17, the product of H atom delivery to the more open end of the intermediate allylic radical. Oxidative cleavage followed by α-methylenation delivered jungermannenone B (18).

D. F. Taber, Org. Chem. Highlights 2017, August 28.