Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 23, 2019
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Pericoannosin C (Dai/Tang), Protoilludenol (Takasu), Daphenylline (Qiu), Atropurpuran (Xu), Vinigrol (Luo), Morphine (Barriault)

Jungui Dai of the Institute of Materia Medica and Yefeng Tang of Tsinghua University prepared the Z alkene of 1 by Wharton-Grob fragmentation of a precursor 3-mesyloxy cyclohexanone. Diels-Alder cycloaddition led to 2, that was carried on to pericoannosin C (3) (Org. Lett. 2019, 21, 1794. DOI: 10.1021/acs.orglett.9b00371).

Kiyosei Takasu of Kyoto University designed the Diels-Alder addition of 4 with 5 to give the trisubstituted silyl enol ether, that under the reaction conditions equilibrated to the more stable tetrasubstituted silyl enol ether. Cycloaddition with 6 then led to 7, with the full skeleton of protoilludenol 8 (Org. Lett. 2019, 21, 3954. DOI: 10.1021/acs.orglett.9b01089).

Tetrasubstituted alkenes such as 9 are reluctant participants in Diels-Alder cycloaddition. Nevertheless, Fayang G. Qiu of the Guangzhou Institutes of Biomedicine and Health showed that cyclization to 10 proceeded cleanly, leading to daphenylline 11 (Angew. Chem. Int. Ed. 2019, 58, 5754. DOI: 10.1002/anie.201902268).

Atropurpuran (14), isolated from the Chinese flower Aconitum hemsleyanum var. atropurpureum, contains two fused bicyclo[2.2.2]octanes. Jing Xu of the Southern University of Science and Technology assembled this unusual skeleton by the oxidative cyclization of 12 to 13 (J. Am. Chem. Soc. 2019, 141, 3435. DOI: 10.1021/jacs.9b00391).

Vinigrol (17), isolated from a fungal strain in Japan, is an antagonist of tissue necrosis factor α. Tuoping Luo of Peking University assembled the diaxially-bridged cis decalin skeleton of 17 by the transannular cyclization of 15 to 16 (J. Am. Chem. Soc. 2019, 141, 3440. DOI: 10.1021/jacs.9b00621).

The enone 20 from the addition of 18 to 19 very readily aromatizes. Louis Barriault of the University of Ottawa found conditions that allowed the isolation of 20, that was immediately reduced to the allylic alcohol on the way to morphine (21) (Org. Lett. 2019, 21, 1347. DOI: 10.1021/acs.orglett.9b00044).

D. F. Taber, Org. Chem. Highlights 2019, December 23.