Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 13, 2015
Douglass F. Taber
University of Delaware

Enantioselective Synthesis of Alcohols and Amines: The Doi Synthesis of Apratoxin C

Hiromitsu Takayama of Chiba University used (Org. Lett. 2014, 16, 5000. DOI: 10.1021/ol502265q) the Itsuno-Corey protocol to reduce the enone 1 to the allylic alcohol 2. Peiming Gu of Ningxia University developed (Org. Lett. 2014, 16, 5339. DOI: 10.1021/ol502608d) a Cu catalyst that cyclized the prochiral 3 to 4 in high ee. Xiaoming Feng of Sichuan University effected (Org. Lett. 2014, 16, 3938. DOI: 10.1021/ol501737a) enantioselective Baeyer-Villiger oxidation of the racemic cyclopentanone 5, converting one enantiomer to the δ-lactone 6.

The velocity of catalytic osmylation is often limited by slow turnover of the intermediate osmate ester. Koichi Narasaka, then at the University of Tokyo, showed (Chem. Lett. 1988, 1721. DOI: 10.1246/cl.1988.1721) that the efficiency of the transformation was improved by the addition of stoichiometric phenyl boronic acid. Kilian Muñiz, now at ICIQ Tarragona, established (Chem. Eur. J. 2005, 11, 3951. DOI: 10.1002/chem.200500095) that this acceleration also worked with Sharpless asymmetric dihydroxylation. D. Christopher Braddock of Imperial College London took advantage (Chem. Commun. 2014, 50, 13725. DOI: 10.1039/C4CC06234E) of these observations, converting myrcene 7 selectively to the cyclic boronate 8.

Michael P. Doyle of the University of Maryland developed (J. Org. Chem. 2014, 79, 12185. DOI: 10.1021/jo5013674) a Rh catalyst for the ene reaction of 9 with 10 to give 11. Adriaan J. Minnaard of the University of Groningen devised (Chem. Eur. J. 2014, 20, 14250. DOI: 10.1002/chem.201404458) a Cu catalyst that mediated the face selective addition of 13 to 12, establishing the oxygenated quaternary center of 14. Tomonori Misaki and Takashi Sugimura of the University of Hyogo used (Chem. Lett. 2014, 43, 1826. DOI: 10.1246/cl.140713) Michael addition of 15 to 16 to construct the oxygenated quaternary center of 17. Jon C. Antilla of the University of South Florida assembled (Chem. Commun. 2014, 50, 14187. DOI: 10.1039/C4CC06520D) the δ-lactone 20 by adding the diene 19 to the β-keto ester 18. Zhiyong Wang of the University of Science and Technology of China reported (Org. Lett. 2014, 16, 3564. DOI: 10.1021/ol5015009) related results.

Jonathan A. Ellman of Yale University achieved (Angew. Chem. Int. Ed. 2014, 53, 11329. DOI: 10.1002/anie.201406971) substantial enantioselectivity in the addition of thioacetic acid 22 to the nitroalkene 21. Subhash P. Chavan of the National Chemistry Laboratory prepared (Tetrahedron Lett. 2014, 55, 5905. DOI: 10.1016/j.tetlet.2014.08.078) the allylic amine 25 by reduction of the aziridine 24. Petri M. Pihko of the University of Jyväskylä prepared (Org. Lett. 2014, 16, 5152. DOI: 10.1021/ol5025025) the Mannich adduct 28 by adding the β-keto ester 26 to the imine 27. Stéphane P. Roche of Florida Atlantic University and Eric N. Jacobsen of Harvard University described (J. Am. Chem. Soc. 2014, 136, 12872. DOI: 10.1021/ja5075163) a related study (not illustrated) catalytically converting α-chloroglycinates to α-amino esters in high ee. Takashi Ooi of Nagoya University prepared (ACS Catal. 2014, 4, 4304. DOI: 10.1021/cs501369z) the α-quaternary allylic amine 31 by coupling 29 with the imine 30.

The cyanobacteria-derived cyclodepsipeptides, exemplified by Apratoxin C (35), show promising anticancer activity. Takayuki Doi of Tohoku University prepared (J. Org. Chem. 2014, 79, 8000. DOI: 10.1021/jo501130b) 34, the starting material for 35, by adding acetone (33) to isobutyraldehyde (32) on a multi-gram scale.

D. F. Taber, Org. Chem. Highlights 2015, July 13.