Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 18, 2016
Douglass F. Taber
University of Delaware

C-O Ring Construction: Artemone (Vosburg), Diospongin B (Hall), Exiguolide (Song), Cucujolide XI (Schulz), Phoracantholide I (Goeke), and Clavosolide A (Breit)

Artemone (3) is an aromatic sesquiterpene isolated from the Indian sage Artemisia pallens. En route to 3, David A. Vosburg of Harvey Mudd College cyclized (Synthesis 2015, 47, 2599. DOI: 10.1055/s-0034-1380684) linalool (1) to lilac aldehyde (2) with high diastereocontrol.

Dennis G. Hall of the University of Alberta used (Org. Lett. 2015, 17, 4156. DOI: 10.1021/acs.orglett.5b01906) a Cr catalyst to add 5 to 4, leading to 6 in high ee. Depending on the Pd catalyst used, bromobenzene could be added to 6 to give either regioisomer of the coupled product. The adduct 7 was carried on to Diospongin B (8).

Zhenlei Song of the West China School of Pharmacy assembled (Org. Lett. 2015, 17, 4706, DOI: 10.1021/acs.orglett.5b02162; Chem. Commun. 2015, 51, 14925, DOI: 10.1039/C5CC02448J) the tetrahydropyran 11 by the brominative Prins cyclization of 10 with 9. A second brominative Prins, this time on a dienyl alcohol, led to (-)-Exiguolide (12).

Recently developed Mo catalysts are effective for the ring-closing metathesis even of terminal alkynes. Stefan Schulz of the Technische Universitšt Braunschweig took advantage (Org. Lett. 2015, 17, 5004. DOI: 10.1021/acs.orglett.5b02461) of this, cyclizing 13 to the alkyne that was selectively hydrogenated to Cucujolide XI (14).

Quanrui Wang of Fudan University and Andreas Goeke of Givaudan Shanghai observed (Eur. J. Org. Chem. 2015, 4982. DOI: 10.1002/ejoc.201500654) that the opening of 15 with 16 led to 17 and 18, enantiomeric at the secondary methyl group, in a ratio of 85:15. This problem was solved in the following step, when on exposure to trifluoroacetic acid 17 was cleanly desilylated while 18 mostly was not. Hydrogenation of the desilylated product converted it to (-)-Phoracantholide I (19).

Bernhard Breit of the Albert-Ludwigs-Universitšt Freiburg showed (Angew. Chem. Int. Ed. 2015, 54, 15530. DOI: 10.1002/anie.201411402) that the chiral Rh catalyst they developed could dimerize the allenyl carboxylic acid 20 cleanly to 21, with high control of the two newly-introduced stereogenic centers. The diol 21 was readily carried on to Clavosolide A (22).

D. F. Taber, Org. Chem. Highlights 2016, April 18.