Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 14, 2014
Douglass F. Taber
University of Delaware

Enantioselective Synthesis of Alcohols and Amines: The Zhu Synthesis of (+)-Trigonoliimine A

The enantioselective epoxidation of a terminal alkene 1 has been a long-sought goal of organic synthesis. Albrecht Berkessel of the University of Cologne devised (Angew. Chem. Int. Ed. 2013, 52, 8467. DOI: 10.1002/anie.201210198) a Ti catalyst that mediated the conversion of 1 to 2. Zhi Li of the National University of Singapore described (Chem. Commun. 2013, 49, 11572. DOI: 10.1039/C3CC46675B) a cell-based system that effected the enantioselective epoxidation of 3 to 4.

Antonio Mezzetti of ETH Zürich and Francesco Santoro of Firmenich SA carried out (Angew. Chem. Int. Ed. 2013, 52, 10352. DOI: 10.1002/anie.201304844) the enantioselective hydrogenation of 5 to the allylic alcohol 6. Elena Fernández of the Universitat Rovira i Virgilli and Andrew Whiting of Durham University devised (Org. Lett. 2013, 15, 4810. DOI: 10.1021/ol4022029) a protocol for the enantioselective conjugate borylation of the imine derived from 7, leading to the secondary alcohol 8. Benjamin List of the Max-Planck-Institute, Mülheim and Choong Eui Song of Sungkyunkwan University condensed (Angew. Chem. Int. Ed. 2013, 52, 12143. DOI: 10.1002/anie.201306297) the thioester 10 with the aldehyde 9 to give the alcohol 11.

Toshiro Harada of the Kyoto Institute of Technology developed (Org. Lett. 2013, 15, 4198. DOI: 10.1021/ol4019248) a general procedure for the enantioselective addition of a terminal alkene 12 to an aldehyde 9. As illustrated by the preparation of 13, this appears to be tolerant of a variety of organic functional groups. Professor Harada also established (Chem. Eur. J. 2013, 19, 17707. DOI: 10.1002/chem.201303619) a protocol for the enantioselective addition of an alkyne 14 to an aldehyde to give the branched product 15.

Chun-Jiang Wang and Xumu Zhang of Wuhan University hydrogenated (Angew. Chem. Int. Ed. 2013, 52, 8416. DOI: 10.1002/anie.201302943) the alkyne 16 to the protected allylic amine 17. Keiji Maruoka of Kyoto University effected (J. Am. Chem. Soc. 2013, 135, 18036. DOI: 10.1021/ja4099627) the enantioselective α-amination of an aldehyde 18, to give 19. David W. C. MacMillan of Princeton University described (J. Am. Chem. Soc. 2013, 135, 11521. DOI: 10.1021/ja406181e) a complementary approach, not illustrated. David J. Fox of the University of Warwick reduced (Chem. Commun. 2013, 49, 10022. DOI: 10.1039/C3CC46070C) the ketone 20, then rearranged the resulting secondary alcohol to the α-amino amide 21.

α-Quaternary amines are particularly sought after. Xiao-Ying Xu and Li-Xin Wang of the Chengdu Institute of Organic Chemistry added (Eur. J. Org. Chem. 2013, 2864. DOI: 10.1002/ejoc.201201701) the aldehyde 22 to the azodicarboxylate 23 to give 24. Yuko Otani of the University of Tokyo and Kei Takeda of Hiroshima University found (Angew. Chem. Int. Ed. 2013, 52, 12956. DOI: 10.1002/anie.201306443) that depending on the choice of base, the readily-available enantiomerically enriched 25 could be acylated to give either enantiomer of 26.

Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne developed (Angew. Chem. Int. Ed. 2013, 52, 12714. DOI: 10.1002/anie.201306663) yet another approach to α-quaternary amines. The enantioselective addition of the isonitrile 27 to the vinyl selenone 28 established the key quaternary center of (+)-Trigonoliimine A (30).

D. F. Taber, Org. Chem. Highlights 2014, July 14.