Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 23, 2018
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Robinson and Morimoto Syntheses of Lepadiformine A

Lal Dhar S. Yadav of the University of Allahabad used (Tetrahedron Lett. 2017, 58, 3814. DOI: 10.1016/j.tetlet.2017.08.042) visible light to activate the addition of 2 to 1 to give the azetidine 3. Patrick Pale and Aurélien Blanc of the Université de Strasbourg prepared (Tetrahedron 2017, 73, 5096. DOI: 10.1016/j.tet.2017.06.067) the azetidine 5 by ring contraction of 4.

Daniel B. Werz of the TU Braunschweig combined (J. Org. Chem. 2017, 82, 9235. DOI: 10.1021/acs.joc.7b01631) 6 and 7 to give the pyrrolidine 8. Sherry R. Chemler of the State University of New York at Buffalo effected (J. Am. Chem. Soc. 2017, 139, 9515. DOI: 10.1021/jacs.7b05680) the oxidative cyclization of 9 to 10. Philippe Renaud of the University of Bern devised (J. Org. Chem. 2017, 82, 12318. DOI: 10.1021/acs.joc.7b02150) a protocol for the reductive coupling of the lactam 11 with an alkyl copper species, leading to the pyrrolidine 12. Sung-Gon Kim of Kyonggi University showed (J. Org. Chem. 2017, 82, 8179. DOI: 10.1021/acs.joc.7b01533) that the Hayashi catalyst effectively mediated the addition of 14 to the imine 13, leading to 15.

Anne Wadouachi of the Université de Picardie prepared (Synlett 2017, 28, 2174. DOI: 10.1055/s-0036-1590829) the fully-substituted piperidine 17 by hydrolysis of 16 followed by reduction. Amandine Guérinot and Janine Cossy of ESPCI Paris observed (Eur. J. Org. Chem. 2017, 6160. DOI: 10.1002/ejoc.201700977) high diastereocontrol in the cyclization of 18 to 19. Daniel Romo of Baylor University cyclized (J. Org. Chem. 2017, 82, 13161. DOI: 10.1021/acs.joc.7b02235) 20 to 21 in high enantiomeric excess. Erick M. Carreira of the ETH Zürich established (Angew. Chem. Int. Ed. 2017, 56, 11515. DOI: 10.1002/anie.201706374) that an Ir catalyst was effective for directing the addition of 22 to 23, leading, after reduction, to 24 with high stereocontrol.

Dan Yang of the University of Hong Kong carried out (Synlett 2017, 28, 1570. DOI: 10.1055/s-0036-1588502) the oxidative cylization of 25 to the bicyclic 26. William P. Unsworth of the University of York (Chem. Eur. J. 2017, 23, 13314. DOI: 10.1002/chem.201703316) and Dean J. Tantillo of the University of California, Davis and Andrei K. Yudin of the University of Toronto (Chem. Eur. J. 2017, 23, 13319. DOI: 10.1002/chem.201703616) independently developed the ring expansion of 27 to 29 by combination with 28.

Lepadiformine A (32), isolated from the marine tunicate Clavelina lepadiformis, shows moderate but selective cytotoxicity. Andrea Robinson of Monash University (J. Org. Chem. 2017, 82, 8497. DOI: 10.1021/acs.joc.7b01135) and Yoshiki Morimoto of Osaka City University (Chem. Eur. J. 2017, 23, 9535. DOI: 10.1002/chem.201701475) independently reported syntheses of 32 designed to pass through the Kibayashi intermediate 30, to take advantage of the cyclization of that amino alcohol in one step to 31. This cyclization, proceeding with inversion at the alcohol stereocenter, was reported (J. Org. Chem. 1992, 57, 5990. DOI: 10.1021/jo00048a037) 25 years ago, but has been little used in alkaloid synthesis.

D. F. Taber, Org. Chem. Highlights 2018, April 23.