Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 22, 2016
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Guanacastepene N (Sha), Pterosin N (Uang), CJ-16,264 (Nicolaou), Maoecrystal V (Gong/Yang), Weisaconitine D (Sarpong)

Dragoslav Vidovíc of Nanyang Technological University devised (Chem. Eur. J. 2015, 21, 11344. DOI: 10.1002/chem.201502205) an aluminum complex that efficiently catalyzed the Diels-Alder addition of 1 to 2 to make 3. Karl Anker Jorgensen of Aarhus University developed (Angew. Chem. Int. Ed. 2015, 54, 13630. DOI: 10.1002/anie.201507348) a primary amine catalyst that transiently converted cyclopentenone 4 into a reactive diene, to which 5 added to form 6.

Chin-Kang Sha of the National Tsing Hua University prepared (Org. Lett. 2015, 17, 3486. DOI: 10.1021/acs.orglett.5b01498) the ester 7 in high ee by lipase-mediated acetylation of the racemic alcohol. Cycloaddition converted 7 to 8, that was carried on to the diterpene Guanacastepene N (9).

Highly-substituted benzene derivatives can also be assembled by Diels-Alder cycloaddition. Biing-Jiun Uang, also of the National Tsing Hua University, showed (Eur. J. Org. Chem. 2014, 4351. DOI: 10.1002/ejoc.201402234) that 11, from cyclization of 10, was readily aromatized to (-)-Pterosin N (12).

The antibiotic CJ-16,264 (15) was reported to have impressive antibiotic activity. In the course of correcting the structure to 15, K. C. Nicolaou of Rice University prepared (Angew. Chem. Int. Ed. 2015, 54, 9203. DOI: 10.1002/anie.201504337) the dimeric macrolactone 13 and cyclized it to 14.

Jian-xian Gong and Zhen Yang of Peking University Shenzhen Graduate School envisioned (Chem. Asian. J. 2015, 10, 1874. DOI: 10.1002/asia.201500564) that the phenol of the relatively simple lactone 16 could be oxidized to the α-acetoxy cyclohexadienone [not illustrated], that in turn could cyclize to 17, substantially along the way to the antineoplastic diterpene Maoecrystal V (18). Even though the oxidation led to the expected ~ 1:1 mixture of diastereomers, only one of which cyclized to the desired 17, it could be produced in sufficient quantity to enable to synthesis of 18.

The complex C-18 and C-19 diterpene alkaloids have long presented a challenge for total synthesis. Richmond Sarpong of the University of California, Berkeley developed (Nature 2015, 528, 493. DOI: 10.1038/nature16440) a general approach to both classes of alkaloids, illustrated by the cyclization of 19 to 20 in the course of the synthesis of Weisaconitine D (21).

D. F. Taber, Org. Chem. Highlights 2016, August 22.