Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 13, 2018
Douglass F. Taber
University of Delaware

Metal-Mediated Carbocyclic Construction: The Nakada Synthesis of Paclitaxel (Taxol®)

Christopher Uyeda of Purdue University developed conditions for the addition of the alkylidene carbene derived from 2 to the diene 1 to give the alkylidene cyclopropane 3 (J. Am. Chem. Soc. 2017, 139, 11686. DOI: 10.1021/jacs.7b05901). Vy M. Dong of the University of California, Irvine cyclized the prochiral aldehyde 4 to the cyclobutanone 5 in high ee (J. Am. Chem. Soc. 2017, 139, 10208. DOI: 10.1021/jacs.7b05327).

Erik J. Alexanian of the University of North Carolina devised a ligand system that enabled the cyclization of 6 to cyclopentane 7 (J. Am. Chem. Soc. 2017, 139, 11595. DOI: 10.1021/jacs.7b06794). Moíses Gulías, José L. Mascareñas and Fernando López of the Universidade de Santiago de Compostela cyclized 8 directly to 9 (Angew. Chem. Int. Ed. 2017, 56, 9541. DOI: 10.1002/anie.201705105). Ei-ichi Negishi of Purdue University further expanded the range of Zr-mediated carbocyclizations, converting 10 to 11 in high ee (Angew. Chem. Int. Ed. 2017, 56, 11502. DOI: 10.1002/anie.201706198). Subrata Ghosh of the Indian Association for the Cultivation of Science, Jadavpur used Nugent/RajanBabu conditions to cyclize 12 to 13 (J. Org. Chem. 2017, 82, 7675. DOI: 10.1021/acs.joc.7b01179).

The ketone 15 looks like it should be derived from a natural product. Eric M. Simmons and Boguslaw Mudryk of Bristol-Myers Squibb found it more practical to optimized enantioselective conjugate addition to cyclohexenone 14 (Org. Process Res. Dev. 2017, 21, 1659. DOI: 10.1021/acs.oprd.7b00253). Laurent Pouységu and Stéphane Quideau of the University of Bordeaux prepared the substituted cyclohexanone 18 by oxidation of the phenol 16 followed by the addition of 17 (J. Org. Chem. 2017, 82, 11816. DOI: 10.1021/acs.joc.7b02366). In related work, Shingo Harada and Tetsuhiro Nemoto of Chiba University cyclized the diazo amide 19 to the cyclohexadienone 20 (J. Am. Chem. Soc. 2017, 139, 10188. DOI: 10.1021/jacs.7b04813). Hideki Abe of Japan Women's University and Hisanaka Ito of the Tokyo University of Pharmacy and Life Sciences found the Reformatsky/Honda conditions effective for the cyclization of 21 to 22 (Org. Lett. 2017, 19, 5996. DOI: 10.1021/acs.orglett.7b03038).

Professor Uyeda also devised the carbonylative rearrangement of the norbornadiene 23 to the ketone 24 (J. Am. Chem. Soc. 2017, 139, 13672. DOI: 10.1021/jacs.7b08691). Lili Lin and Xiaoming Feng of Sichuan University established a complementary enantioselective approach to diquinanes, the domino Michael addition of 26 to 25 to give 27 (Org. Chem. Front. 2017, 4, 2012. DOI: 10.1039/C7QO00408G).

Paclitaxel (Taxol®) (30) is one of the most important clinical anti-cancer agents of the 21st century. Masahisa Nakada of Waseda University developed a route to 30, a key step of which was the cyclization of 28 to 29 (J. Synth. Org. Jpn. 2017, 75, 1102. DOI: 10.5059/yukigoseikyokaishi.75.1102).

D. F. Taber, Org. Chem. Highlights 2018, August 13.