Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 11, 2019
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Kazmaier Synthesis of Luminmycin A

Radim Hrdina and Peter R. Schreiner of Justus Liebig University observed high regioselectivity in the aziridination of 1, leading to 2 (Chem. Sci. 2019, 10, 3324. DOI: 10.1039/C8SC05733H). Ryan Gianatassio of Biogen prepared the azetidine 5 by opening 3, generated in situ, with the Grignard reagent 4 (Org. Lett. 2019, 21, 2060. DOI: 10.1021/acs.orglett.9b00321). Varinder K. Aggarwal of the University of Bristol described a parallel investigation (J. Am. Chem. Soc. 2019, 141, 4573. DOI: 10.1021/jacs.9b01513).

Stephen L. Buchwald of MIT cyclized 6 to 7 in high ee (Angew. Chem. Int. Ed. 2019, 58, 3407. DOI: 10.1002/anie.201814331). Michael J. Krische of the University of Texas observed clean inversion in the cyclization of 8, prepared from the corresponding aldehyde in a single step, to the pyrrolidine 9 (Org. Lett. 2019, 21, 2493. DOI: 10.1021/acs.orglett.9b00508). Masayuki Wasa of Boston College coupled 10 with 11 to give 12, perhaps via a hydride transfer mechanism (J. Am. Chem. Soc. 2018, 140, 10593. DOI: 10.1021/jacs.8b06699). Yoshihiro Oonishi and Yoshihiro Sato of Hokkaido University used a Rh catalyst to cyclize 13 to 14 in high ee (Angew. Chem. Int. Ed. 2019, 58, 8736. DOI: 10.1002/anie.201902832).

John F. Bower, also of the University of Bristol, used a Pd catalyst to cyclize 15 to the piperidine 16. Pyrrolidines could also be prepared using this protocol (J. Am. Chem. Soc. 2019, 141, 3356. DOI: 10.1021/jacs.8b12689). Oliver Reiser of the Universitńt Regensburg showed that the ee of 17 was maintained through the addition of 18 and ring opening to give 19 (Angew. Chem. Int. Ed. 2019, 58, 3594. DOI: 10.1002/anie.201813716). Adrian P. Dobbs of the University of Greenwich assembled 22 by combining 20 with 21 (Org. Lett. 2019, 21, 350. DOI: 10.1021/acs.orglett.8b03283). Via participation by the proximal alkene, Yves BlÚriot of the UniversitÚ de Poitiers deprotected 23 selectively to 24 (Org. Lett. 2019, 21, 4821. DOI: 10.1021/acs.orglett.9b01712).

Ian D. Williams and Jianwei Sun of the Hong Kong University of Science and Technology prepared the lactam 27 by combining 25 with 26 (Angew. Chem. Int. Ed. 2019, 58, 6776. DOI: 10.1002/anie.201902866). Kosuke Namba of Tokushima University used proline to cyclize 28, leading, after reduction, to the bicyclic amino alcohol 29 (Org. Lett. 2019, 21, 2620. DOI: 10.1021/acs.orglett.9b00607).

Luminmycin A (32), isolated from the enterobacterium Photorhabdus luminescens, shows potent activity against both colon carcinoma and pancreatic cancer. En route to 32, Uli Kazmaier of Saarland University oxidized 30, then used the Pirrung protocol to cyclize the resulting aldehyde to 31 (Eur. J. Org. Chem. 2019, 3163. DOI: 10.1002/ejoc.201900460).

D. F. Taber, Org. Chem. Highlights 2019, November 11.