Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 24, 2016
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Zhu Synthesis of Strictamine

Hua-Dong Xu and Mei-Hua Shen of Changzhou University prepared (Angew. Chem. Int. Ed. 2016, 55, 2540. DOI: 10.1002/anie.201510096) the aziridine 2 by the diastereoselective 4+2 cycloaddition of the intermediate arizine (not illustrated) from the thermolysis of the alkenyl azide 1. Phil S. Baran of Scripps/La Jolla assembled (Science 2016, 351, 241. DOI: 10.1126/science.aad6252) the azetidine 4 by cyclizing 3 to the azabicyclobutane (not illustrated), then opening it with the metalated amine.

Olivier Baudoin, now at the University of Basel, cyclized (Angew. Chem. Int. Ed. 2016, 55, 2805. DOI: 10.1002/anie.201511457) the amide 5 to the lactam 6. Lionel Perrin and David Gueyrard of the Université Claude Bernard Lyon 1 developed (Eur. J. Org. Chem. 2016, 2944. DOI: 10.1002/ejoc.201600349) a protocol for the modifed Julia cyclization of 7 to the indolizidine 8. Christopher J. Moody of the University of Nottingham observed (Angew. Chem. Int. Ed. 2016, 55, 3749. DOI: 10.1002/anie.201511433) high diastereoselectivity in the construction of 11 by the addition of 9 to 10. Mauro F. A. Adamo of the Royal College of Surgeons in Ireland used (Chem. Commun. 2016, 52, 1697. DOI: 10.1039/C5CC08105J) an organocatalyst to guide the relative and absolute configuration of the addition of 13 to 12 to make 14.

Piperidines can be prepared by the ring expansion of pyrrolidines, as exemplified by the transformation of 15 to 16 reported (J. Org. Chem. 2015, 80, 6936. DOI: 10.1021/acs.joc.5b01230) by F. Couty of the Université de Versailles. Andrej Kolarovic of the Slovak University of Technology crystallized (Tetrahedron Lett. 2016, 57, 1079. DOI: 10.1016/j.tetlet.2016.01.086) the dominant diastereomer 19 from the combination of 17 with 18. Hajime Ito of Hokkaido University accomplished (J. Am. Chem. Soc. 2016, 138, 4338. DOI: 10.1021/jacs.6b01375) the reduction of 20 followed by asymmetric hydroboration to give 21. The C-H insertion process that converted 22 to 23, as described (Angew. Chem. Int. Ed. 2016, 55, 4547. DOI: 10.1002/anie.201510729) by Gwilherm Evano of the Université libre de Bruxelles, is presumably proceeding by hydride abstraction followed by cyclization of the resulting carbocation.

Asunción Barbero of the University of Valladolid established (Org. Lett. 2016, 18, 1972. DOI: 10.1021/acs.orglett.6b00538) a general diastereoselective route to azepanes, as illustrated by the combination of 24 and 25 to give 26. Ganesh Pandey of Centre of Biomedical Research observed (Org. Lett. 2016, 18, 1558. DOI: 10.1021/acs.orglett.6b00374) high diastereoselectivity in the intramolecular addition of the enone of 27 to the 1,3-dipole generated from the silyl nitrile.

Strictamine (31) was isolated from the dita tree Astonia scholaris, long used in traditional Indian medicine. Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne assembled (Angew. Chem. Int. Ed. 2016, 55, 3500. DOI: 10.1002/anie.201511638) the tricyclic core of 31 by the oxidative cyclization of 29 to 30. The precursor to 29 is prochiral, so it may be possible to develop an asymmetric version of this synthesis.

D. F. Taber, Org. Chem. Highlights 2016, October 24.