Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 11, 2011
Douglass F. Taber
University of Delaware

C-O Ring Construction: The Theodorakis Synthesis of (-)-Englerin A

Liming Zhang of the University of California, Santa Barbara described (J. Am. Chem. Soc. 2010, 132, 8550. DOI: 10.1021/ja1033952) the remarkable transformation of a propargyl alcohol 1 into the oxetanone 2. The transformation proceeded without loss of ee, as did the ring expansion of 3 to 5 reported (J. Org. Chem. 2010, 75, 6229. DOI: 10.1021/jo101330p) by Peter R. Schreiner of Justus-Liebig University, Giessen and Andrey A. Fokin of the Kiev Polytechnic Institute.

Takeo Taguchi of the Tokyo University of Pharmacy and Life Sciences developed (Chem. Commun. 2010, 46, 8728. DOI: 10.1039/C0CC02438D) a catalyst for the stereoselective conjugate addition of 7 to 6. Mitsuru Shindo of Kyushu University devised (Org. Lett. 2010, 12, 5346. DOI: 10.1021/ol102407k) the thioester 10, that condensed smoothly with an α-hydroxy ketone 9 to deliver the lactone 11.

Zili Chen of the Renmin University of China and Lin Guo of the Beijing University of Aeronautics and Astronautics developed (Org. Lett. 2010, 12, 3468. DOI: 10.1021/ol1012923) the diastereoselective double addition of propargyl alcohol 13 to 12 to give 14. Jian-Wu Xie of Zhejiang Normal University uncovered (J. Org. Chem. 2010, 75, 8716. DOI: 10.1021/jo101935k) the catalyzed enantioselective addition of 16 to 15 to give the dihydrofuran 17.

James S. Panek of Boston University extended (Org. Lett. 2010, 12, 4624. DOI: 10.1021/ol1019629) the utility of the enantiomerically-pure allenic nucleophile 19, adding it to the acceptor 18 to give 20 with both ring and sidechain stereocontrol. Biswanath Das of the Indian Institute of Chemical Technology, Hyderabad showed (Tetrahedron Lett. 2010, 51, 6011. DOI: 10.1016/j.tetlet.2010.09.049) that the epoxide of the tartrate-derived acetonide 21 could be rearranged to the fully-substituted, differentially-protected tetrahydrofuran 22.

Paul E. Floreancig of the University of Pittsburgh uncovered (Angew. Chem. Int. Ed. 2010, 49, 5894. DOI: 10.1002/anie.201002281) the highly stereocontrolled oxidative cyclization of 22 to 23. Dirk Menche of the University of Heidelberg found (Angew. Chem. Int. Ed. 2010, 49, 9270. DOI: 10.1002/anie.201003304) that the Pd-mediated addition of 24 to 25 also proceeded with high diastereocontrol.

Dipolar cycloaddition to a furan is of increasing importance in target-directed synthesis. Emmanuel A. Theodorakis of the University of California, San Diego added (Org. Lett. 2010, 12, 3708. DOI: 10.1021/ol1015652) the diazo ester 27, prepared from the inexpensive chiral auxiliary pantolactone, to the furan 28. The product diastereomers were readily separated, enabling efficient access to the potent antineoplastic agent (-)-Englerin A (30).

D. F. Taber, Org. Chem. Highlights 2011, April 11.