Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 21, 2014
Douglass F. Taber
University of Delaware

Enantioselective Construction of Alkylated Centers: The Rawal Synthesis of (+)-Fornicin C

Kazuaki Kudo of the University of Tokyo showed (Angew. Chem. Int. Ed. 2013, 52, 11585. DOI: 10.1002/anie.201305004) that the dienyl aldehyde 1 could be reduced to the saturated aldehyde 2 with high ee. Alexandre Alexakis of the University of Geneva effected (Angew. Chem. Int. Ed. 2013, 52, 12701. DOI: 10.1002/anie.201306541) conjugate addition to the unsaturated amide 3 to give 4 in high ee. Professor Alexakis also carried out (Chem. Eur. J. 2013, 19, 11352. DOI: 10.1002/chem.201300538) enantioselective conjugate addition to the alkynyl nitro alkene 5, leading to 6. Gerrit J. Poelarends of the University of Groningen found (Chem. Eur. J. 2013, 19, 14407. DOI: 10.1002/chem.201302351) that the enzyme 4-oxalocrotonate tautomerase mediated the conjugate addition of acetaldehyde to a nitroalkene 7 to deliver the aldehyde 8 in high ee.

Tohru Yamada of Keio University developed (Chem. Commun. 2013, 49, 8371. DOI: 10.1039/C3CC44610G) an enantioselective Cu catalyst for the Claisen rearrangement of 9 to 10. Shi-Kai Tian of USTC Hefei made (Chem. Commun. 2013, 49, 8190. DOI: 10.1039/C3CC44914A) the primary amine of 11 a leaving group, coupling 11 with 12 to make 13. David W. C. MacMillan of Princeton University alkylated (J. Am. Chem. Soc. 2013, 135, 11756. DOI: 10.1021/ja406356c) the aldehyde 14 with the boronic acid 15, to give 16 in high ee. Paolo Melchiorre of ICIQ Tarragona effected (Nature Chem. 2013, 5, 750. DOI: 10.1038/nchem.1727) the enantioselective construction of the quaternary center of 19 by alkylation of the aldehyde 17.

Other methods for the enantioselective construction of quaternary alkylated centers have also been put forward. Varinder K. Aggarwal of the University of Bristol elaborated (J. Am. Chem. Soc. 2013, 135, 16054. DOI: 10.1021/ja409100y) the inexpensive secondary ester 20 into the alkylated product 21. Jianwei Sun of the Hong Kong University of Science and Technology cyclized (Angew. Chem. Int. Ed. 2013, 52, 13593. DOI: 10.1002/anie.201306801) the prochiral diol 22 to 23 in high ee. Amir H. Hoveyda of Boston College effected (Angew. Chem. Int. Ed. 2013, 52, 8156. DOI: 10.1002/anie.201304035) enantioselective conjugate addition to the enone 24 to give 25. Xiaoming Feng of Sichuan University devised (Angew. Chem. Int. Ed. 2013, 52, 10883. DOI: 10.1002/anie.201305478) a catalyst for the addition of the bulky α-diazo ester 26 into the α-keto ester 27, leading to 28.

(+)-Fornicin C (32) was isolated from the traditional Chinese medicinal plant Ganoderma fornicatum. Viresh H. Rawal of the University of Chicago prepared (J. Am. Chem. Soc. 2013, 135, 16050. DOI: 10.1021/ja409012q) 32 by enantioselective conjugate addition of the CO2 surrogate 30 to the enone 29.


D. F. Taber, Org. Chem. Highlights 2014, July 21.