Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 18, 2014
Douglass F. Taber
University of Delaware

Metal-mediated C-C Ring Construction: The Carreira Synthesis of (+)-Asperolide C

Djamaladdin G. Musaev and Huw M. L. Davies of Emory University effected (Chem. Sci. 2013, 4, 2844. DOI: 10.1039/C3SC50425E) enantioselective cyclopropanation of ethyl acrylate 2 with the α-diazo ester 1 to give 3 in high ee. Philippe Compain of the Université de Strasbourg used (J. Org. Chem. 2013, 78, 6751. DOI: 10.1021/jo400732a) SmI2 to cyclize 4 to the cyclobutanol 5.

Jianrong (Steve) Zhou of Nanyang Technological University effected (Chem. Commun. 2013, 49, 11758. DOI: 10.1039/C3CC47551D) enantioselective Heck addition of 7 to the prochiral ester 6 to give the cyclopentene 8. Liu-Zhu Gong of USTC Hefei added (Org. Lett. 2013, 15, 3958. DOI: 10.1021/ol4017386) the Rh enolate from the enantioselective ring expansion of the α-diazo ester 9 to the nitroalkene 10, to give 11 in high de.

Stephen P. Fletcher of the University of Oxford set (Angew. Chem. Int. Ed. 2013, 52, 7995. DOI: 10.1002/anie.201303202) the cyclic quaternary center of 14 by the enantioselective conjugate addition to 12 of the alkyl zirconocene derived from 13. Alexandre Alexakis of the University of Geneva reported (Chem. Eur. J. 2013, 19, 15226. DOI: 10.1002/chem.201302856) high ee from the conjugate addition of alkenyl Al reagents (not illustrated) to 12. Paultheo von Zezschwitz of Philipps-Universität Marburg prepared (Adv. Synth. Catal. 2013, 355, 2651. DOI: 10.1002/adsc.201300524) the silyl enol ether 17 by trapping the intermediate from the conjugate addition of 16 to 15.

Stefan Bräse of the Karlsruhe Institute of Technology effected (Eur. J. Org. Chem. 2013, 7110. DOI: 10.1002/ejoc.201300752) conjugate addition to the prochiral dienone 18 to give the highly substituted cyclohexenone 19. Ping Tian and Guo-Qiang Lin of the Shanghai Institute of Organic Chemistry cyclized (J. Am. Chem. Soc. 2013, 135, 11700. DOI: 10.1021/ja404593c) 20 to the kinetic, less stable epimer of the diketone 21.

Rh-mediated intramolecular C-H insertion has been a powerful tool for the construction of cyclopentane derivatives. We found (J. Org. Chem. 2013, 78, 9772. DOI: 10.1021/jo4014996) that the Rh carbene derived from 22 was discriminating enough to target the more nucleophilic C-H bond, leading to the cyclohexanone 23. Kozo Shishido of the University of Tokushima observed (Org. Lett. 2013, 15, 3666. DOI: 10.1021/ol401543b) high diastereoselectivity in the intramolecular Heck cyclization of 24 to 25.

Two protocols for the titanocene-mediated construction of polycarbacyclic systems have been developed. José Justicia and Juan M. Cuerva of the University of Granada observed (Chem. Eur. J. 2013, 19, 14484. DOI: 10.1002/chem.201302575) that only one of the two diastereomers of 26 cyclized, leading to the highly-functionalized 27. A. Fernández-Mateos of the Universidad de Salamanca found (J. Org. Chem. 2013, 78, 9571. DOI: 10.1021/jo401646g) that while the nitrile 28 cyclized to the 6/4 cis fused cyclobutanone 29, the nitrile one carbon longer cyclized to give the complementary 6/5 trans ring system (not illustrated).

Erick M. Carreira of ETH Zürich added (Angew. Chem. Int. Ed. 2013, 52, 12166. DOI: 10.1002/anie.201307187) an allyl silane terminator to the enantioselective Ir catalysis he had developed. The triene 30 so designed cyclized cleanly to 31, that was carried on to (+)-Asperolide C (32).

D. F. Taber, Org. Chem. Highlights 2014, August 18.