Organic Chemistry Portal
Organic Chemistry Highlights

Monday, March 27, 2023
Douglass F. Taber
University of Delaware

Functional Group Protection: The Pronin Synthesis of Quassin

Elena V. Gusvskaya of the Universidade Federal de Minas Gerais and Matthias Beller of the Leibniz-Institut für Katalyse e.V. used benzaldehyde to convert the alcohol 1 to the benzyl ether 2 (Chem. Eur. J. 2022, 28, e202103903. DOI: 10.1002/chem.202103903). Yu Tang and Biao Yu of the Shanghai Institute of Organic Chemistry selectively converted the diol 3 to the methyl ether 4 (Synthesis 2022, 54, 2373. DOI: 10.1055/a-1731-3852). Chien-Fu Lian of the National Chung Hsing University achieved similar selectivity in converting the diol 5 to the monobenzoate 6 (Org. Lett. 2022, 24, 4207. DOI: 10.1021/acs.orglett.2c01467). Rima Thakur of the National Institute of Technology Patna showed that the cyanomethyl ether of 7 could be deprotected to the alcohol 8, leaving the benzyl ethers intact (Org. Biomol. Chem. 2022, 20, 4030. DOI: 10.1039/D2OB00338D).

Le-Wu Zhan and Bin-dong Li of the Nanjing University of Science and Technology devised an easily-scaled protocol for converting the alcohol 1 to the nitrate ester 9 (Org. Process Res. Dev. 2022, 26, 174. DOI: 10.1021/acs.oprd.1c00388). Using a pentadinium catalyst, Xin Zhang and Choon-Hong Tan of Nanyang Technological University achieved high diastereoselectivity in the combination of menthol 10 with the sulfinic acid 11 to give the sulfinate ester 12 (Nature 2022, 604, 298. DOI: 10.1038/s41586-022-04524-4).

Susumu Saito of Nagoya University assembled the 2-oxazoline 14, a protected form of the acid and, after reduction, the aldehyde, by cyclization of the hydroxy amide 13 (J. Org. Chem. 2022, 87, 243. DOI: 10.1021/acs.joc.1c02318). Michael Szostak of Rutgers University, Newark and Tieqiao Chen of Hainan University used KI to promote the transamidation of 15 with aniline to give the amide 16 (Angew. Chem. Int. Ed. 2022, 61, e202202794. DOI: 10.1002/anie.202202794). Thomas Scattolin of Mirati Therapeutics used mercaptoethanol 18 to selectively deprotect the bis-urethane 17, cleaving the Cbz group to give 19, with the Boc group intact (Org. Lett. 2022, 24, 3736. DOI: 10.1021/acs.orglett.2c01410). Dayong Sang and Juan Tian of the Jinchu University of Technology used AlI3 to debenzylate the acyl sulfonamide 20, leading to 21 (J. Org. Chem. 2022, 87, 3586. DOI: 10.1021/acs.joc.1c03133).

Andrew J. Carnell of the University of Liverpool used an enzyme preparation to convert the diacid 22 to the monomethyl ester 23 (Angew. Chem. Int. Ed. 2022, 61, e202117324. DOI: 10.1002/anie.202117324). Meng Tang of Lanzhou University oxidized the tosylhydrazone derived from the aldehyde 24 to the acyl hydrazide 25. On exposure to base, 25 would be converted back to the aldehyde 24, by the McFadyen-Stevens reaction (J. Org. Chem. 2022, 87, 3845. DOI: 10.1021/acs.joc.1c03037).

Quassin (28) was isolated from the tropical bitterwood tree Quassia amara, long used as a medicinal plant. In preparation for a convergent assembly of 28, Sergey V. Pronin of the University of California, Irvine epoxidized the enone 26, then heated the product to release the enone 27 (J. Am. Chem. Soc. 2022, 144, 118. DOI: 10.1021/jacs.1c12283).

D. F. Taber, Org. Chem. Highlights 2023, March 27.