Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 26, 2015
Douglass F. Taber
University of Delaware

C-H Functionalization: The Maimone Synthesis of Podophyllotoxin

Matthias Beller of the Universitšt Rostock developed (Angew. Chem. Int. Ed. 2014, 53, 6477. DOI: 10.1002/anie.201402287) a Rh catalyst for the acceptorless dehydrogenation of an alkane 1 to the alkene 2. Bhisma K. Patel of the Indian Institute of Technology Guwahati effected (Org. Lett. 2014, 16, 3086. DOI: 10.1021/ol5011906) oxidation of cyclohexane 3 to the allylic benzoate 5.

Justin Du Bois of Stanford University devised (Chem. Sci. 2014, 5, 656. DOI: 10.1039/C3SC52649F) an organocatalyst that mediated the hydroxylation of 6 to 7. Vladimir Gevorgyan of the University of Illinois, Chicago hydrosilylated (Nature Chem. 2014, 6, 122. DOI: 10.1038/nchem.1841) 8 to give an intermediate that after Ir-catalyzed intramolecular C-H functionalization followed by oxidation was converted to the diacetate 9. Sukbok Chang of KAIST used (J. Am. Chem. Soc. 2014, 136, 4141. DOI: 10.1021/ja501014b) the methoxime of 10 to direct selective amination of the adjacent methyl group, leading to 11. John F. Hartwig of the University of California, Berkeley effected (J. Am. Chem. Soc. 2014, 136, 2555. DOI: 10.1021/ja411912p) diastereoselective amination of 13 to 14.

David W. C. MacMillan of Princeton University accomplished (J. Am. Chem. Soc. 2014, 136, 6858. DOI: 10.1021/ja502639e) β-alkylation of the aldehyde 15 with acrylonitrile 16 to give 17. Yunyang Wei of the Nanjing University of Science and Technology alkenylated (Chem. Sci. 2014, 5, 2379. DOI: 10.1039/C4SC00093E) cyclohexane 3 with the styrene 18, leading to 19.

Bin Wu of the Kunming Institute of Botany described (Org. Lett. 2014, 16, 480. DOI: 10.1021/ol403364k) the Pd-mediated cyclization of 20 to 21. Similar results using Cu catalysis were reported (Angew. Chem. Int. Ed. 2014, 53, 3496, DOI: 10.1002/anie.201311105; 3706, DOI: 10.1002/anie.201311263) by Yoichiro Kuninobu and Motomu Kanai of the University of Tokyo and by Haibo Ge of IUPUI. Jin-Quan Yu of Scripps La Jolla constructed (J. Am. Chem. Soc. 2014, 136, 5267. DOI: 10.1021/ja501689j) the lactam 24 by γ-alkenylation of the amide 22 with 23, followed by cyclization.

Philippe Dauban of CNRS Gif-sur-Yvette prepared (Eur. J. Org. Chem. 2014, 66. DOI: 10.1002/ejoc.201301174) the useful crystalline chiron 26 by asymmetric amination of the enol triflate 27. Matthew J. Gaunt of the University of Cambridge showed (J. Am. Chem. Soc. 2014, 136, 8851. DOI: 10.1021/ja504361y) that the phenylative cyclization of 28 to 30 proceeded with near-perfect retention of absolute configuration.

Podophyllotoxin 34 is the core of the clinically-important anti-cancer agents etoposide and teniposide. Thomas J. Maimone, also of the University of California, Berkeley devised (Angew. Chem. Int. Ed. 2014, 53, 3115. DOI: 10.1002/anie.201311112) a two-step conversion of 31 to 34 that took advantage of recent developments in Pd-catalyzed C-H arylation. This approach will allow the incorporation of almost any aryl group.

D. F. Taber, Org. Chem. Highlights 2015, January 26.