Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 21, 2017
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Yaoshanenolide B (Stratakis), 1-Tuberculosinyl Adenosine (Minaard), penicillone B (Liao), (-)-Neocosmosin A (Cho), Salvinorin (Forsyth), Dihydroajaconine (Liu/Qin)

Manolis Stratakis of the University of Crete observed (Org. Lett. 2016, 18, 4982. DOI: 10.1021/acs.orglett.6b02446) that the racemic dieonophile 2 added to natural (R)-α-(-)-phellandrene (1) to give a mixture of four separable diastereomers, two major and two minor. One of the two major diastereomers, 3, was carried on to (+)-yaoshanenolide B.

1-Tuberculosinyl adenosine (8) shows promise as a biomarker for tuberculosis infection. Adriaan J. Minnaard of the University of Groningen assembled (J. Org. Chem. 2018, 81, 6686. DOI: 10.1021/acs.joc.6b01332) the core 7 of 8 by the highly diastereoseoective addition of 6 to the diene 5.

En route to penicillone B (12), Chun-Chen Liao of the National Tsing Hua University oxidized (J. Org. Chem. 2016, 81, 11421. DOI: 10.1021/acs.joc.6b02055) 9 in the presence of crotyl alcohol (10) to give 11 as the major (3.3:1) diastereomer. Because of a misassignment in the literature, the authors chose to take not 11, but the minor diastereomer (not illustrated) forward in the synthesis, leading to 12, the enantiomer of the natural product.

Diels-Alder cycloaddition can also be used to construct aromatic rings. Cheon-Gyu Cho of Hanyang University demonstrated (Org. Lett. 2016, 18, 5126. DOI: 10.1021/acs.orglett.6b02575) the facile cyclization of 13 to 14, that was carried on to (-)-neocosmosin A (15).

Tethering allows even simple alkenes such as 16 to participate in Diels-Alder cycloaddition. En route to (-)-salvinorin (18), Craig J. Forsyth of the Ohio State University cyclized (Chem. Eur. J. 2016, 22, 17983. DOI: 10.1002/chem.201604853) 16 to 17.

Arene oxidation to the reactive dienone can be carried out even sensitive substrates such as 19. The cyclization of 19 to 20 reported (Angew. Chem. Int. Ed. 2016, 55, 15667. DOI: 10.1002/anie.201609882) by Xiao-Yu Liu and Yong Qin of Sichuan University established a general entry to the diterpene alkaloids, including dihydroajaconine 21.

We note with sadness the passing of Professor István E. Markó of the Université Catholique de Louvain, whose creative work was cited many times in these pages.

D. F. Taber, Org. Chem. Highlights 2017, August 21.