Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 29, 2019
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Penaresidin B (Yakura), Febrifugine (Harrity), Crinane (Zhu), Castoramine (Tokuyama), Hosieine A (Wood), Amathaspiramide F (Kim)

Takayuki Yakura of the University of Toyama showed that the mesylate 1 readily cyclized to 2. The azetidine 2 was carried on to penaresidin B (3) (Tetrahedron 2018, 74, 4578. DOI: 10.1016/j.tet.2018.07.023).

Joseph P. A. Harrity of the University of Sheffield observed that the Sakurai opening of the epoxide 4 with 5 proceeded to give a ~ 1:1 mixture of diastereomers, suggesting significant carbocation involvement. The easily-separable trans diastereomer of 6 was carried on to febrifugine (7) (Org. Biomol. Chem. 2018, 16, 4159. DOI: 10.1039/C8OB00935J). Yashwant D. Vankar of the Indian Institute of Technology Kanpur reported the reactions of a related epoxide (Eur. J. Org. Chem. 2018, 6574. DOI: 10.1002/ejoc.201801241).

Using oxidizing conditions, Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne cyclized the prochiral diene 8 to 9 in high ee. The sulfonamide 9 was elaborated to the Amaryllidaceae alkaloid crinane (10) (Angew. Chem. Int. Ed. 2018, 57, 1995. DOI: 10.1002/anie.201712521). Martin G. Banwell of the Australian National University developed an alternative route to crinane (J. Org. Chem. 2018, 83, 8493. DOI: 10.1021/acs.joc.8b01088).

Hidetoshi Tokuyama of Tohoku University added crotyl magnesium chloride 12 to the intermediate from the reduction of 11 to give the piperidine 13 with remarkable regio- and diastereocontrol. They used the same strategy to set the last stereocenter in the penultimate step of the synthesis of castoramine (14) (Synlett 2018, 29, 1786. DOI: 10.1055/s-0037-1610435).

In the course of a synthesis of hosieine A (17), John L. Wood of Baylor University cyclized 15 to 16 with high diastereocontrol. The enantiomerically-enriched 15 was prepared by Au-catalyzed cyclization of a racemic tertiary propargylic pivalate (Angew. Chem. Int. Ed. 2018, 57, 7664. DOI: 10.1002/anie.201804076).

En route to amathaspiramide F (21), Sanghee Kim of Seoul National University bridge the proline starting material to form 18. Alkylation with 19 followed by anionic rearrangement of the resulting ammonium salt than delivered 20 (Org. Lett. 2018, 20, 6121. DOI: 10.1021/acs.orglett.8b02568).

D. F. Taber, Org. Chem. Highlights 2019, April 29.