Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 14, 2023
Douglass F. Taber
University of Delaware

Metal-mediated C-C Ring Construction: The Sarpong Synthesis of 15-Hydroxypatchoulol

John P. Wolfe of the University of Michigan constructed the cyclobutene 3 by coupling the enol triflate 1 with diethyl malonate 2 (Org. Lett. 2022, 24, 8208. DOI: 10.1021/acs.orglett.2c03308). Xiaohua Liu and Xiaoming Feng of Sichuan University achieved significant enantiomeric excess in the Mg-catalyzed addition of the allene 4 to the alkene 5 to give the cyclobutene 6 (Angew. Chem. Int. Ed. 2022, 61, e202211596. DOI: 10.1002/anie.202211596).

While attempted intermolecular alkylation of aldehydes often leads to C-O rather than C-C bond formation, the cyclization of the bromoaldehyde 7 to the cyclopentane 8 by Jean-Luc Vasse of the Université de Reims Champagne Ardenne is a reminder that intramolecular alkylation of an aldehyde is often efficient (Org. Biomol. Chem. 2022, 20, 5803. DOI: 10.1039/D2OB01073A). Xinqiang Fang of the Fujian Institute of Research on the Structure of Matter expanded the prochiral cyclobutane 9 to the cyclopentanone 10 in high ee (ACS Catal. 2022, 12, 12036. DOI: 10.1021/acscatal.2c03623). Abbas Hassan of Quaid-i-Azam University assembled the cyclopentene 13 by adding the diazonium salt 12 to the prochiral cyclopentene 11 (Tetrahedron Lett. 2022, 111, 154204. DOI: 10.1016/j.tetlet.2022.154204). Matthew J. Cook of Montana State University used a Claisen-Sakurai strategy to cyclize the enol ether 14 to the cyclopentene 15 (J. Org. Chem. 2022, 87, 12250. DOI: 10.1021/acs.joc.2c01397).

Shu-Li You of the Shanghai Institute of Organic Chemistry prepared the enone 18 by alkylating the β-naphthol 16 with the allylic carbonate 17 (Org. Lett. 2022, 24, 8031. DOI: 10.1021/acs.orglett.2c03262). Qing-An Chen of the Dalian Institute of Chemical Physics dimerized isoprene 19 in the presence of the heterocycle 20, leading to the cyclohexene 21 (Nature Catal. 2022, 5, 708. DOI: 10.1038/s41929-022-00825-z). Zhi-Xiang Yu of Peking University effected the ring expansion of the cyclobutanone 22 to the cyclohexenone 23 (J. Am. Chem. Soc. 2022, 144, 21457. DOI: 10.1021/jacs.2c04244). Yoshitaka Matsushima of the Tokyo University of Agriculture observed high diastereoselectivity in the reductive cyclization of the keto aldehyde 24 to the highly-substituted cyclohexanol 25 (Tetrahedron Lett. 2022, 106, 154060. DOI: 10.1016/j.tetlet.2022.154060).

Professor Liu and Liming Zhang of the University of California, Santa Barbara cyclized the β-naphthol 26 to the cyclohexenone 27 (Angew. Chem. Int. Ed. 2022, 61, e202207518. DOI: 10.1002/anie.202207518). Ming Yang of Lanzhou University effected the catalytic Ti(III) cyclization of the epoxide 28 to the decalin 29 (Nature Commun. 2022, 13, 6633. DOI: 10.1038/s41467-022-34404-4).

Patchoulol ("patchouli alcohol") is a sesquiterpene alcohol found in patchouli oil, an important material in perfumery. Richmond Sarpong of the University of California, Berkeley devised a route to the patchoulol skeleton, leading to 15-hydroxypatchoulol (33). A key step in the synthesis was the Pd-mediated coupling of the dichloride 31 with the tertiary alcohol 30, leading to 32. The alcohol 30 was prepared by Ti(III) cyclization of carvone epoxide (J. Am. Chem. Soc. 2022, 144, 19253. DOI: 10.1021/jacs.2c09201).

D. F. Taber, Org. Chem. Highlights 2023, August 14.