Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 17, 2012
Douglass F. Taber
University of Delaware

Metal-Mediated Carbocyclic Construction: The Whitby Synthesis of (+)-Mucosin

Erick M. Carreira of ETH-Zürich generated (Org. Lett. 2012, 14, 2162. DOI: 10.1021/ol300688p) ethyl diazoacetate in situ in the presence of the alkene 1 and an iron catalyst, to give the cyclopropane 3. Joseph M. Fox of the University of Delaware inserted (Chem. Sci. 2012, 3, 1589. DOI: 10.1039/C2SC01134D) the Rh carbene derived from 5 into the alkene 4 to give the cyclopropene 6, without β-hydride elimination. Masaatsu Adachi and Toshio Nishikawa of Nagoya University reduced (Chem. Lett. 2012, 41, 287. DOI: 10.1246/cl.2012.287) the enone 7 to give the cyclobutanol 8.

Intramolecular ketene cycloaddition has been limited to very electron rich acceptor alkenes. Xiao-Ping Cao and Yong-Qiang Tu of Lanzhou University devised (Chem. Sci. 2012, 3, 1975. DOI: 10.1039/C2SC20109G) a protocol that converted 9 into the cyclobutanone 10, with high diastereocontrol. The intermediate is the tosylhydrazone of the ketone, so a reductive workup would lead to the corresponding cycloalkane.

Koichi Mikami of the Tokyo Institute of Technology added (J. Am. Chem. Soc. 2012, 134, 10329. DOI: 10.1021/ja3032345) alkyl cuprates to the prochiral enone 11 to give the enolate trapping product 13 in high ee and with high diastereocontrol. Marcus A. Tius of the University of Hawaii found (Angew. Chem. Int. Ed. 2012, 51, 5727. DOI: 10.1002/anie.201201724) a Pd catalyst for the Nazarov cyclization of 14 to 15. Antoni Riera and Xavier Verdaguer of the Universitat de Barcelona prepared (Org. Lett. 2012, 14, 3534. DOI: 10.1021/ol301545e) 16 by enantioselective Pauson-Khand addition to tetramethyl norbornadiene. Conjugate addition followed by retro Diels-Alder could potentially lead to the cyclopentenone 17.

The intermolecular Pauson-Khand cyclization often gives mixtures of regioisomers. José Barluenga of the Universidad de Oviedo demonstrated (Angew. Chem. Int. Ed. 2012, 51, 183. DOI: 10.1002/anie.201105362) an alternative, the addition of an alkenyl lithium 19 to the Fischer carbene 18, leading to 20.

Jian-Hua Xie and Qi-Lin Zhou of Nankai University hydrogenated (Adv. Synth. Catal. 2012, 354, 1105; DOI: 10.1002/adsc.201100898, see also Org. Lett. 2012, 14, 2714, DOI: 10.1021/ol300913g) the ketone 21 under epimerizing conditions, to give the alcohol 22. Kozo Shishido of the University of Tokushima observed (Tetrahedron Lett. 2012, 53, 145. DOI: 10.1016/j.tetlet.2011.10.151) that the intramolecular Heck cyclization of 23 proceeded with high diastereocontrol. Zhi-Xiang Yu of Peking University devised (Org. Lett. 2012, 14, 692. DOI: 10.1021/ol2031526) a Rh catalyst for the cyclocarbonylation of 25 to 26. En route to (-)-atrop-Abyssomycin C, Filip Bihelovic and Radomir N. Saicic of the University of Belgrade cyclized (Angew. Chem. Int. Ed. 2012, 51, 5687. DOI: 10.1002/anie.201108223) the bromoaldehyde 27 to the cyclohexane 29.

Richard J. Whitby of the University of Southampton prepared (Chem. Commun. 2012, 48, 3332. DOI: 10.1039/C2CC17915F) the eicosanoid (+)-Mucosin 34 by cyclizing the triene 30 with stoichometric zirconocene ($ .50/mmol). The Zr in 31 has an empty orbital, like boron, allowing the subsequent transformation. Many other applications can be envisioned for this equilibrating cyclozirconation.

D. F. Taber, Org. Chem. Highlights 2012, December 17.