Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 14, 2015
Douglass F. Taber
University of Delaware

Metal-Mediated C-C Ring Construction: The Lei Synthesis of (-)-Huperzine Q

Following the Szymoniak protocol, Morwenna S. M. Pearson-Long and Philippe Bertus of the Université du Maine added (Synthesis 2015, 47, 992. DOI: 10.1055/s-0034-1379978) the Grignard reagent 2 to the nitrile 1 to give the cyclopropyl amine 3. Chen-Guo Feng of the Shanghai Institute of Organic Chemistry prepared (Chem. Commun. 2015, 51, 8773. DOI: 10.1039/C5CC02023A) the cyclobutane 6 by enantioselective conjugate addition of 5 to the unsaturated ester 4.

Martin Kotora of Charles University showed (Eur. J. Org. Chem. 2015, 2868. DOI: 10.1002/ejoc.201500248) that the zirconacycle from the eneyne 7 reacted with the aldehyde 8 to give, after iodination, the alcohol 9. Xiaoming Feng of Sichuan University used (Angew. Chem. Int. Ed. 2015, 54, 1608. DOI: 10.1002/anie.201409572) a scandium catalyst to effect the intramolecular Roskamp cyclization of 10 to 11. Celia Dominguez of CHDI observed (Org. Lett. 2015, 17, 1401. DOI: 10.1021/acs.orglett.5b00207) that the double alkylation of the ester 12 with the dibromide 13 proceeded with high diastereoselectivity, to give 14. Hirokazu Tsukamoto of Tohoku University cyclized (Chem. Commun. 2015, 51, 8027. DOI: 10.1039/C5CC02176F) 15 to 16 in high ee.

Daniel J. Weix of the University of Rochester found (J. Am. Chem. Soc. 2015, 137, 3237. DOI: 10.1021/jacs.5b01909) that under the influence of an enantiomerically-pure Ti catalyst, the organonickel species derived from 18 opened the prochiral epoxide 17 to give 19 in high ee. John F. Bower of the University of Bristol optimized (J. Am. Chem. Soc. 2015, 137, 463. DOI: 10.1021/ja511335v) conditions for the highly diastereoselective Rh-mediated cyclocarbonylation of 20 to 21. Margaret A. Brimble of the University of Auckland initiated (J. Org. Chem. 2015, 80, 2231. DOI: 10.1021/jo502748s) the construction of the cyclohexenone 24 by the diastereoselective addition of 23 to the unsaturated ester 22. Olivier Baslé and Marc Maduit of ENSC Rennes devised (Chem. Eur. J. 2015, 21, 993. DOI: 10.1002/chem.201405765) conditions for the preparation of 26 by enantioselective conjugate addition to the cyclohexenone 25.

Yoshito Kishi of Harvard University demonstrated (Tetrahedron Lett. 2015, 56, 3220. DOI: 10.1016/j.tetlet.2014.12.024) that the carbenoid generated from the epoxide 27 cyclized to 28 with high diastereoselectivity. Wenjung Tang, also of the Shanghai Institute of Organic Chemistry, developed (Angew. Chem. Int. Ed. 2015, 54, 3033. DOI: 10.1002/anie.201411817) a Pd catalyst for the diastereoselective (because it is enantioselective) cyclization of 29 to 30.

Carbonyl-alkene metathesis has only rarely been used in target-directed synthesis. A key step in the assembly (Angew. Chem. Int. Ed. 2015, 54, 1011. DOI: 10.1002/anie.201409503) of (-)-Huperzine Q (33) by Xiaoguang Lei of Peking University was the selective cyclization of 31 to 32.

D. F. Taber, Org. Chem. Highlights 2015, December 14.