Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 8, 2024
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Wang/Huo/Zong Synthesis of Flustramine B

Zi-Qiang Rong of the Northwestern Polytechnical University prepared the pyrrolidine 3 by the Co-catalyzed reductive coupling of the pyrroline 1 with the iodide 2 (J. Am. Chem. Soc. 2023, 145, 15456. DOI: 10.1021/jacs.3c03900). Santosh J. Gharpure of the Indian Institute of Technology Bombay cyclized the enyne 4 to the 2,5-dialkyl pyrrolidine 5 (Org. Lett. 2023, 25, 5850. DOI: 10.1021/acs.orglett.3c02115). Haruhiko Fuwa of Chuo University reported related results (Chem. Commun. 2023, 59, 10121. DOI: 10.1039/D3CC02453A). Xiaohua Liu and Xiaoming Feng of Sichuan University assembled the proline derivative 8 by ring-expanding the prochiral azetidine 6 with the diazoamide 7 (Angew. Chem. Int. Ed. 2023, 62, e202307249. DOI: 10.1002/anie.202307249). Ping Tian and Qinghua Li of the Shanghai University of Traditional Medicine and Liang Yin of the Shanghai Institute of Organic Chemistry constructed the 2,2,4,5-tetrasubstituted pyrrolidine 11 by the Cu-catalyzed 1,3-dipolar cycloaddition of the protected alanine 10 to the enyne 9 (Nature Commun. 2023, 14, 4688. DOI: 10.1038/s41467-023-40409-4).

Via site-directed mutagenesis, Yao Nie of Jiangnan University developed enzymes to reduce the piperidone 12 to either enantiomer of the alcohol 13 (Adv. Synth. Catal. 2023, 365, 4205. DOI: 10.1002/adsc.202300904). Enabled by the StackPhos ligand they developed, Aaron Aponick of the University of Florida coupled the pyridine 14 with TMS acetylene 15, leading to the alkylated dihydropyridine 16 (Angew. Chem. Int. Ed. 2023, 62, e202312967. DOI: 10.1002/anie.202312967). Stephen P. Fletcher of the University of Oxford acylated pyridine under reducing conditions to give 17, then coupled that with an arylboronic acid, leading to the 3-aryl piperidine 18 (J. Am. Chem. Soc. 2023, 145, 14221. DOI: 10.1021/jacs.3c05044). Mario Waser of Johannes Kepler University Linz used a chiral isothiourea to mediate the coupling of the ester 19 with the mesylate 20, leading after cyclization to the piperidinone 21 (Eur. J. Org. Chem. 2023, 26, e202300982. DOI: 10.1002/ejoc.202300982).

Jianrong Steve Zhou of Peking University Shenzhen Graduate School coupled the iododiene 22 with the bromide 23, leading to the azepane 24 (J. Am. Chem. Soc. 2023, 145, 16464. DOI: 10.1021/jacs.3c02829). Macarena MartÝnez-BailÚn and Francesca Cardona of the UniversitÓ di Firenze effected the reductive cyclization of the acetal 25 to the polyhydroxylated azepane 26 (Org. Lett. 2023, 25, 5833. DOI: 10.1021/acs.orglett.3c02087).

En route to racemic sparteine, Sarah E. Reisman of the California Institute of Technology prepared the quinolizidine 28 by coupling pyridine 14 with glutaryl chloride 27 (Org. Lett. 2023, 25, 8230. DOI: 10.1021/acs.orglett.3c03242). Karl Anker J°rgensen of Aarhus University used the Hayashi-J°rgensen catalyst to mediate the assembly of the bicyclic enone 31 by the combination of the pyridinium salt 29 with crotonaldehyde 30 (Chem. Eur. J. 2023, 29, e202301830. DOI: 10.1002/chem.202301830).

Flustramine B (35), isolated from the bryozoan Flusta foliacea, possesses skeletal and smooth-muscle relaxant activity. In an optimized approach to 35, Chao Wang of Nanjing Tech University and Shuaidong Huo and Lili Zong of Xiamen University used a bisguanidinium catalyst under ambient conditions to alkylate the oxindole 32 with prenyl bromide 33, leading to 34 (ACS Catal. 2023, 13, 15708. DOI: 10.1021/acscatal.3c03812).

D. F. Taber, Org. Chem. Highlights 2024, April 8.