Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 23, 2012
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Harrity Synthesis of Quinolizidine (-)-217A

David M. Jenkins of the University of Tennessee devised (J. Am. Chem. Soc. 2011, 133, 19342. DOI: 10.1021/ja2090965) an iron catalyst for the aziridination of an alkene 1 with an aryl azide 2. Yoshiji Takemoto of Kyoto University cyclized (Org. Lett. 2011, 13, 6374. DOI: 10.1021/ol2026747) the prochiral oxime derivative 4 to the azirine 5 in high ee. Organometallics added to 5 syn to the pendant ester.

Hyeung-geun Park of Seoul National University used (Adv. Synth. Catal. 2011, 353, 3313. DOI: 10.1002/adsc.201100542) a chiral phase transfer catalyst to effect the enantioselective alkylation of 6 to 7. Yian Shi of Colorado State University showed (Org. Lett. 2011, 13, 6350. DOI: 10.1021/ol202527g) that a chiral Bronsted acid mediated the enantioselective cyclization of 8 to 9. Mattie S. M. Timmer of Victoria University of Wellington and Bridget L. Stocker of Malaghan Institute of Medical Research effected (J. Org. Chem. 2011, 76, 9611. DOI: 10.1021/jo201151b) the oxidative cyclization of 10 to 11. They also showed (Tetrahedron Lett. 2011, 52, 4803, not illustrated. DOI: 10.1016/j.tetlet.2011.07.044) that the same cyclization worked well to construct piperidine derivatives. Jose L. Vicario of the Universidad del País Vasco extended (Adv. Synth. Catal. 2011, 353, 3307. DOI: 10.1002/adsc.201100432) organocatalysis to the condensation of 12 with 13, to give the pyrrolidine 14.

Jinxing Ye of the East China University of Science and Technology used (Adv. Synth. Catal. 2011, 353, 343. DOI: 10.1002/adsc.201000647) the same Hayashi catalyst to condense 15 with 16, to give 17. André B. Charette of the Université de Montreal expanded (Org. Lett. 2011, 13, 3830. DOI: 10.1021/ol201349k) 18, prepared by Petasis-Mannich coupling followed by ring-closing metathesis, to the piperidine 20. Marco Bella of the “Sapienza” University of Roma effected (Org. Lett. 2011, 13, 4546. DOI: 10.1021/ol2017406) enantioselective addition of 22 to the prochiral 21, to give 23. Ying-Chun Chen of Sichuan University and Chun-An Fan of Lanzhou University cyclized (Adv. Synth. Catal. 2011, 353, 2721. DOI: 10.1002/adsc.201100282) 24 to 25 in high ee.

Andreas Schmid of TU Dortmund showed (Adv. Synth. Catal. 2011, 353, 2501. DOI: 10.1002/adsc.201100396) that ω-laurolactam hydrolases could be used to cyclize the ester 26, but not the free acid, to the macrolactam 27. After investigating several metal-mediated C-C bond forming alternatives en route to Vaniprevir, Zhiguo J. Song and David M. Tellers of Merck Process settled (J. Org. Chem. 2011, 76, 7804. DOI: 10.1021/jo2011494) on C-N bond formation as the best way to prepare 29.

Joseph P. A. Harrity of the University of Sheffield explored (Chem. Commun. 2011, 47, 9804. DOI: 10.1039/C1CC13048J) the reactivity of the versatile ene sulfonamide 30. Cyclopropanation proceeded with high facial selectivity. Opening of the cyclopropane gave 31, which was carried on to the frog alkaloid Quinolizidine (-)-217 A (32).

D. F. Taber, Org. Chem. Highlights 2012, April 23.