Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 15, 2016
Douglass F. Taber
University of Delaware

Construction of Alkylated Centers: The Weng/Lu Synthesis of Epoxyisoprostane EC

Nozomi Saito and Yoshihiro Sato of Hokkaido University developed (Chem. Asian. J. 2015, 10, 1170. DOI: 10.1002/asia.201403399) an efficient preparation of the ester 1, and hydrogenated it to 2 in high ee. In the course of a synthesis of aliskiren, Pher G. Andersson of Stockholm Universitet reduced the trisubstituted ester 3 to 4 in high ee (Chem. Eur. J. 2015, 21, 7292. DOI: 10.1002/chem.201406523).

Stereogenic centers can also be installed by kinetic protonation. Tomislav Rovis of Colorado State University observed (J. Am. Chem. Soc. 2015, 137, 508. DOI: 10.1021/ja511445x) high ee in the preparation of 7 by the addition of 5 to 6, as did Sanzhong Luo of Beijing National Laboratory for Molecular Sciences (Org. Lett. 2014, 17, 4626. DOI: 10.1021/ol5022178) in the addition of 8 to 9 to give 10.

Stephen P. Fletcher of the University of Oxford extended (Org. Lett. 2015, 17, 912. DOI: 10.1021/acs.orglett.5b00021) the enantioselective addition of alkyl zirconocenes to acyclic acceptors such as 11, leading to 13. Hao Li of the East China University of Science and Technology and Wei Wang of the University of New Mexico showed (J. Am. Chem. Soc. 2015, 137, 2303. DOI: 10.1021/ja511143b) that the styrene 15 was reactive enough to accept the enantioselective addition of the aldehyde 14 to give 16. You Huang of Nankai University devised (Angew. Chem. Int. Ed. 2015, 54, 1621. DOI: 10.1002/anie.201409744) an organocatalyst that mediated the addition of 18 to 17 to give 19. Matthew S. Sigman of the University of Utah found (J. Am. Chem. Soc. 2015, 137, 3462. DOI: 10.1021/ja5130836) that the Heck addition of 20 to 21 delivered 22 in high ee and with high regioselectivity.

Diverse strategies have been reported for the enantioselective assembly of alkylated quaternary centers. Li-Wen Xu of Hangzhou Normal University observed (Chem. Eur. J. 2015, 21, 554. DOI: 10.1002/chem.201405420) remarkable enantioselectivity in the preparation of 25 by the dipolar cycloaddition of 24 to 23. René Peters of the Universität Stuttgart devised (Angew. Chem. Int. Ed. 2015, 54, 2788. DOI: 10.1002/anie.201410933) a Pd catalyst that mediated the face selective addition of 26 to 18 to give 27. Martín Fañanás-Mastral, now at the University of Santiago de Compostela, and Ben L. Feringa of the University of Groningen extended (Chem. Eur. J. 2015, 21, 4209. DOI: 10.1002/chem.201406006) enantioselective allylic coupling to Z-alkenes such as 28, converting it to 29. Ganesh Pandy of the Centre of Biomedical Research established (Org. Lett. 2015, 17, 952. DOI: 10.1021/ol503766) that the enantiomeric excess of 30 was maintained in the Johnson-Claisen rearrangement to 31.

The pathology of oxidative stress is mediated in part by the epoxy isoprostanes, exemplified by EC (36). Jiang Weng and Gui Lu of Sun Yat-Sen University, Guangzhou developed (Chem. Commun. 2015, 51, 10170. DOI: 10.1039/C5CC01077B) a telescoped route to 36, based on the enantioselective conjugate addition of the keto ester 33 to the enal 32, followed by condensation with the phosphorane 34, to give 35.

D. F. Taber, Org. Chem. Highlights 2016, February 15.