Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 20, 2017
Douglass F. Taber
University of Delaware

Alkylated Stereogenic Centers: The Ceroni/Cozzi Synthesis of (-)-Isodehydroxypodophyllotoxin

James P. Morken of Boston College used (J. Am. Chem. Soc. 2016, 138, 7824. DOI: 10.1021/jacs.6b03384) a Ni catalyst to direct the coupling of the prochiral 1 with phenyl magnesium bromide to give 2. Albrecht Berkessel of the University of Cologne opened (Adv. Synth. Catal. 2016, 358, 30. DOI: 10.1002/adsc.201500820) racemic 3 with a lipase and 4 under epimerizing conditions to give 5. Hajime Hirao and Shunsuke Chiba of the Nanyang Technological University showed (Angew. Chem. Int. Ed. 2016, 55, 3719. DOI: 10.1002/anie.201600305) that the reductive decyanation of 6 proceeded with retention of absolute configuration, leading to 7. Stephen L. Buchwald of MIT effected (Nature Chem. 2016, 8, 144. DOI: 10.1038/nchem.2418) one-pot reduction and hydroamination of 8 with 9 to give 10 in high ee.

Michael J. Krische of the University of Texas, Austin assembled (J. Am. Chem. Soc. 2016, 138, 3655. DOI: 10.1021/jacs.6b01078) the alcohol 12 by coupling the allylic acetate 11 with paraformaldehyde. Amir H. Hoveyda, also of Boston College (Angew. Chem. Int. Ed. 2016, 55, 3455. DOI: 10.1002/anie.201600309) and Jie Liu, Yuan-Wei Chen and Dawen Niu of Sichuan University (ACS Catal. 2016, 6, 3381. DOI: 10.1021/acscatal.6b00719) reported related net transformations. Tamio Hayashi, now at A*STAR, prepared (Angew. Chem. Int. Ed. 2016, 55, 1133. DOI: 10.1002/anie.201509778) 15 by adding 14 to 13. Eric Meggers of the Philipps-Universitšt Marburg irraditated (J. Am. Chem. Soc. 2016, 138, 6936. DOI: 10.1021/jacs.6b03399) 16 and 17 in the presence of a Rh catalyst and a photosensitizer to give the conjugate addition product 18. Syuzanna R. Harutyunyan of the Stratingh Institute for Chemistry showed (Science 2016, 352, 433. DOI: 10.1126/science.aaf1983) that the heteroaromatic of 19 was sufficient to activate the alkene for the conjugate addition of 20, leading to 21.

There are other ways of elaborating stereodefined ternary centers. Mark Gandelman of the Technion - Israel Institute of Technology constructed (Chem. Sci. 2016, 7, 2762. DOI: 10.1039/C5SC04378F,) 24 by sequential coupling of 22 with 23 and then with a second organoborane. Jin-Quan Yu of Scripps, La Jolla effected (Science 2016, 351, 252. DOI: 10.1126/science.aad7893) distal activation of the ethyl group of 25 followed by coupling with 26 to give 27.

Hirohisa Ohmiya and Masaya Sawamura of Hokkaido University assembled (Angew. Chem. Int. Ed. 2016, 55, 4777. DOI: 10.1002/anie.201600619) the quaternary stereogenic center of 30 by adding 29 to 28. Ping Fang and Xue-Long Hou of the Shanghai Institute of Organic Chemistry established (Synthesis 2016, 48, 1568. DOI: 10.1055/s-0035-1561574) the quaternary center of 33 by allylating 31 with 32.

In another photochemically-promoted transformation, Paola Ceroni and Pier Giorgio Cozzi of the Universitŗ di Bologna alkylated (ACS Catal. 2015, 5, 5927. DOI: 10.1021/acscatal.5b01573) the aldehyde 34 with the bromoacetate 35 to give, after reduction, the lactone 36. Condensation with the aldehyde 37 followed by cyclization then completed the synthesis of (-)-isodehydroxypodophyllotoxin (38).

D. F. Taber, Org. Chem. Highlights 2017, February 20.