Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 15, 2014
Douglass F. Taber
University of Delaware

Alkene Reactions: The Xu/Loh Synthesis of Vitamin A1

Abdolreza Rezaeifard and Maasoumeh Jafarpour of the University of Birjand devised (J. Am. Chem. Soc. 2013, 135, 10036. DOI: 10.1021/ja405852s) an easily-scaled protocol for the Mo-catalyzed "on water" epoxidation of an alkene 1, using molecular O2. Needing to epoxidize the sensitive alkene 3, we developed (Org. Synth. 2013, 90, 350. DOI: 10.15227/orgsyn.090.0350) a convenient preparation of mmol quantities of the versatile oxidant dimethyldioxirane 4.

Robert H. Grubbs of Caltech showed (Angew. Chem. Int. Ed. 2013, 52, 9751. DOI: 10.1002/anie.201303587) that the Wacker oxidation of internal alkenes could proceed with high regioselectivity, as exemplified by the conversion of 6 to 7. David A. Nicewicz of the University of North Carolina demonstrated (J. Am. Chem. Soc. 2013, 135, 10334. DOI: 10.1021/ja4057294) the remarkable anti-Markovnikov addition of the acid 9 to the alkene 8, to give 10.

Pieter C. A. Bruijnincx and Robertus J. M. Klein Gebbink of the University of Utrecht established (Chem. Eur. J. 2013, 19, 15012. DOI: 10.1002/chem.201301371) a robust one-pot protocol for epoxidation, epoxide hydrolysis and periodate cleavage, for the net oxidative cleavage of the alkene 11 to the aldehydes 12 and 13. Tomoki Ogoshi of Kanazawa University observed (Org. Lett. 2013, 15, 3742. DOI: 10.1021/ol4016546) that permanganate with a phase transfer catalyst could selectively oxidize the linear alkene 14 in the presence of branched alkenes. Davood Azarifar of Bu-Ali Sina University devised (Synlett 2013, 24, 1377. DOI: 10.1055/s-0033-1338947) the reagent 17 as a useful alternative to ozone, as illustrated by the oxidation of 16 to 18. Ning Jiao of Peking University effected (J. Am. Chem. Soc. 2013, 135, 11692. DOI: 10.1021/ja403824y) the unsymmetrical cleavage of the alkene 19 to the nitrile aldehyde 20.

Tiow-Gan Ong of the Academia Sinica added (Org. Lett. 2013, 15, 5358. DOI: 10.1021/ol402644y) 22 to the alkene 21 to give the linear product 23. This could be hydrolyzed to the acid, or reduced and hydrolyzed to the aldehyde. Joost N. H. Reek of the University of Amsterdam isomerized (ACS Catal. 2013, 3, 2939. DOI: 10.1021/cs400872a) the terminal alkene of 24 to the internal alkene, then hydroformylated that directly to give the α-methyl branched aldehyde 25. Laurel L. Schafer of the University of British Columbia developed (Angew. Chem. Int. Ed. 2013, 52, 9144, DOI: 10.1002/anie.201304153; see also Chem. Eur. J. 2013, 19, 8751, DOI: 10.1002/chem.201300992) an improved Ta catalyst that allowed the room temperature aminoalkylation of 26 to give 28. Jianrong (Steve) Zhou of Nanyang Technological University optimized (Chem. Commun. 2013, 49, 10236. DOI: 10.1039/C3CC45911J) the branched Heck reaction, adding 30 to 29 to give 31.

Yun-He Xu of the University of Science and Technology of China and Teck-Peng Loh of that institution and Nanyang Technological University uncovered the Pd-mediated coupling of t-butyl acrylate (Chem. Sci. 2013, 4, 4520, DOI: 10.1039/C3SC52275J; not illustrated) and methyl vinyl ketone 33 (Org. Lett. 2013, 15, 5531. DOI: 10.1021/ol402692t) to an alkene 32 to give the polyene 34. This was a key step in their synthesis of Vitamin A1 (35).

D. F. Taber, Org. Chem. Highlights 2014, September 15.