Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 30, 2014
Douglass F. Taber
University of Delaware

C-C Bond Construction: The Kingsbury Synthesis of (-)-Dihydrocuscohygrine

Akio Baba of Osaka University combined (Chem. Lett. 2013, 42, 1551. DOI: 10.1246/cl.130790) reduction of the acid 1 with subsequent Mukaiyama reaction with the ketene silyl acetal 2 to directly give the coupled product 3. Song-Lin Zhang of Soochow University showed (Chem. Commun. 2013, 49, 10635. DOI: 10.1039/C3CC45611K) that the allyl Sm reagent 5 could be added to an aldehyde 4 under reducing conditions, leading to the alkene 6. In a related development, Patrick Perlmutter of Monash University reduced (Org. Lett. 2013, 15, 4327. DOI: 10.1021/ol401801g) the intermediate lactol from addition of the alkyl lithium reagent 8 to the lactone 7, to give the alcohol 9. Yoshihiro Miyake, now at Nagoya University, and Yoshiaki Nishibayashi of the University of Tokyo added (Chem. Commun. 2013, 49, 7854. DOI: 10.1039/C3CC44438D) the benzyl radical from the decarboxylation of 10 to the acceptor 11. Yasuharu Yoshimi of the University of Fukui (Tetrahedron Lett. 2013, 54, 4324. DOI: 10.1016/j.tetlet.2013.06.020) and Larry E. Overman of the University of California, Irvine (J. Am. Chem. Soc. 2013, 135, 15342. DOI: 10.1021/ja408971t) reported related results.

David Milstein of the Weizmann Institute of Science developed (Angew. Chem. Int. Ed. 2013, 52, 14131. DOI: 10.1002/anie.201306629) an Fe catalyst for the semihydrogenation of an alkyne 13 to the E-alkene 14. Zhi-Xiang Yu of Peking University showed (Org. Lett. 2013, 15, 4634. DOI: 10.1021/ol401607c) that kinetic isomerization of the alkene 15 led selectively to the Z-alkene 16. Umasish Jama of Jadavpur University prepared (Eur. J. Org. Chem. 2013, 4823. DOI: 10.1002/ejoc.201300172) the nitroalkene 18 by condensing nitromethane with the aldehyde 17. Vladimir A. D'yakonov of the Russian Academy of Sciences, Ufa, described (Chem. Commun. 2013, 49, 8401, DOI: 10.1039/C3CC44926B; Tetrahedron 2013, 69, 8516, DOI: 10.1016/j.tet.2013.06.106) the remarkably selective coupling of the allene 19 with the allene 20 to give the Z,Z-diene 21.

Sang-Hyeup Lee of the Catholic University of Daegu assembled (Synlett 2013, 24, 1953. DOI: 10.1055/s-0033-1339482) the ketone 24 by coupling the alkynyl aluminum 23 with the nitrile 22. Jean-Marc Weibel and Patrick Pale of the Universitť de Strasbourg showed (Chem. Eur. J. 2013, 19, 8765. DOI: 10.1002/chem.201300127) that the alkenyl nosylate (p-nitrobenzenesulfonate) 25 coupled smoothly with 26, leading to the enyne 27. Reinhold Zimmer and Hans-Ulrich Reissig of the Freie Universitšt Berlin described (Synthesis 2013, 45, 2752. DOI: 10.1055/s-0033-1339509) similar results with alkenyl nonaflates.

Shengmin Ma of the Shanghai Institute of Organic Chemistry prepared (J. Am. Chem. Soc. 2013, 135, 11517. DOI: 10.1021/ja406135t) the allene 29 by the enantioselective carbonylation of a racemic carbonate 28. Junliang Zhang of East China Normal University and Jianwei Sun of the Hong Kong University of Science and Technology developed (J. Am. Chem. Soc. 2013, 135, 18020. DOI: 10.1021/ja409080v) an organocatalyst for the enantioselective coupling of nitromethane with 30 to deliver 31.

Alkyl diazo intermediates are sufficiently stable that they can be quickly handled. Jason S. Kingsbury, now at Pomona College added (J. Org. Chem. 2013, 78, 10573. DOI: 10.1021/jo401377a) the diazoalkane from 32 twice to formaldehyde to give the ketone 33 with minimal racemization. Reduction followed by reductive methylation then completed the synthesis of the Erythroxylon coca alkaloid (-)-Dihydrocuscohygrine (34).

D. F. Taber, Org. Chem. Highlights 2014, June 30.