Organic Chemistry Portal
Organic Chemistry Highlights

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

Enantioselective Synthesis of Alcohols and Amines: The Fernandes Synthesis of Diosniponol A

Zheng-Wang Qu of the University of Bonn and Yong-Qiang Zhang of Shandong University reduced the prochiral epoxide 1 to the enantiomerically-enriched alcohol 2 (Angew. Chem. Int. Ed. 2023, 62, e202309525. DOI: 10.1002/anie.202309525). Xu Ban and Choon-Hong Tan of Henan Normal University used a bisguanidinium catalyst to mediate the coupling of the N-acyl hydroxylamine 4 with the racemic bromonitrile 3, leading to the α-oxygenated cyanoacetate 5 (Org. Chem. Front. 2023, 10, 5416. DOI: 10.1039/D3QO01332D).

Armando Córdova of Mid Sweden University used a chiral Pd catalyst in conjunction with a Hayashi-Jørgensen amine to alkylate the aldehyde 6 with the allylic acetate 7, leading to the protected diol 8 in high ee (Chem. Eur. J. 2023, 29, e202301725. DOI: 10.1002/chem.202301725). Hajime Hirao of the Chinese University of Hong Kong and Liu-Zhu Gong of the University of Science and Technology of China assembled the lactone 11 by coupling the α-methylene ketone 9 with the aryl ether 10 (J. Am. Chem. Soc. 2023, 145, 22031. DOI: 10.1021/jacs.3c07008).

Lihao Liao and Xiaodan Zhao of Sun-Yat Sen University prepared the azide 14 by combining the alkene 12 with the N-sulfinyl succinimide 13 (Org. Lett. 2023, 25, 6757. DOI: 10.1021/acs.orglett.3c02650). Thomas R. Ward of the University of Basel used an Ir catalyst anchored within strepavidin as a metalloenzyme to cyclize the dioxazoolone 15 to the lactam 16 (J. Am. Chem. Soc. 2023, 145, 16621. DOI: 10.1021/jacs.3c03969). Eric Meggers of Phillips-Universität Marburg used an iron catalyst to rearrange the azanyl ester 17 to the α-amino acid 18 (Eur. J. Org. Chem. 2023, 26, e202300296, DOI: 10.1002/ejoc.202300296; Nature Synthesis 2023, 2, 645, DOI: 10.1038/s44160-023-00267-w). H. Bernhard Schlegel and Hien M. Nguyen of Wayne State University analyzed the Rh-mediated coupling of the trichloroacetimidate 19 with the amine 20, leading to 21 (J. Am. Chem. Soc. 2023, 145, 19642. DOI: 10.1021/jacs.3c04211).

Pei-Qiang Huang of Xiamen University prepared the amine 24 by catalytic reductive coupling of the amide 22 with the alkyne 23 (Nature Commun. 2023, 14, 6251. DOI: 10.1038/s41467-023-41846-x). Alessandra Lattanzi of Università di Salerno effected Knoevenagel condensation of the aldehyde 25 with the cyano sulfone 26, followed by enantioselective epoxidation, and then coupling with aniline, leading to the α-amino ester 27 (Org. Lett. 2023, 25, 5038. DOI: 10.1021/acs.orglett.3c01736). Phil S. Baran of Scripps/La Jolla coupled the redox-active ester 28 with the acid chloride 29 to give the α-amino ketone 30 (Angew. Chem. Int. Ed. 2023, 62, e202315203. DOI: 10.1002/anie.202315203). Mikel Oiarbide, Antonia Mielgo and Claudio Palomo of the Universidad del País Vasco and Jesús M. García of the Universidad Pública de Navarra assembled the α-quaternary nitro alcohol 33 by the urea aminal catalyzed conjugate addition of the nitroalkane 31 to the enone 32 (Org. Lett. 2023, 25, 8590. DOI: 10.1021/acs.orglett.3c03340).

Diosniponol A (36) was isolated from the rhizomes of the liana Dioscorea nipponica of Southeast Asia. En route to 36, Rodney A. Fernandes of the Indian Institute of Technology Bombay devised a protocol for the efficient conversion of the diol from Jacobsen opening of the racemic epoxide 34, allowing efficient production of the enantiomerically-pure epoxide 35 (Org. Biomol. Chem. 2023, 21, 6524. DOI: 10.1039/D3OB00863K).

The initial enantiomerically-pure epoxide 35 and the other enantiomer of the diol from the Jacobsen resolution of racemic 34 were separated by chromatography. The alternative, bromomandelation of the alkene followed by crystallization of the diastereomeric bromomandelates (Enantioselective Assembly of Oxygenated Stereogenic Centers 2008, February 11), might be more readily scaled.

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