Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 16, 2013
Douglass F. Taber
University of Delaware

C-H Functionalization

Konstantin P. Bryliakov of the Boreskov Institute of Catalysis devised (Org. Lett. 2012, 14, 4310. DOI: 10.1021/ol3015122) a manganese catalyst for the selective tertiary hydroxylation of 1 to give 2. Note that the electron-withdrawing Br deactivates the alternative methine H. Bhisma K. Patel of the Indian Institute of Technology, Guwahati selectively oxidized (Org. Lett. 2012, 14, 3982. DOI: 10.1021/ol301756y) a benzylic C-H of 3 to give the corresponding benzoate 4. Dalibor Sames of Columbia University cyclized (J. Org. Chem. 2012, 77, 6689. DOI: 10.1021/jo300635m) 5 to 6 by intramolecular hydride abstraction followed by recombination. Thomas Lectka of Johns Hopkins University showed (Angew. Chem. Int. Ed. 2012, 51, 10580. DOI: 10.1002/anie.201203642) that direct C-H fluorination of 7 occurred predominately at carbons 3 and 5. John T. Groves of Princeton University reported (Science 2012, 337, 1322. DOI: 10.1126/science.1222327) an alternative manganese porphyrin catalyst (not illustrated) for direct fluorination.

C-H functionalization can also be mediated by a proximal functional group. John F. Hartwig of the University of California, Berkeley effected (J. Am. Chem. Soc. 2012, 134, 12422. DOI: 10.1021/ja305596v) Ir-mediated borylation of an ether 9 in the position β to the oxygen, to give 10. Uttam K. Tambar of the UT Southwestern Medical Center devised (J. Am. Chem. Soc. 2012, 134, 18495. DOI: 10.1021/ja307851b) a protocol for the net enantioselective amination of 11, to give 12.

Conversion of a C-H bond to a C-C bond can be carried out in an intramolecular or an intermolecular sense. Kilian Mu˝iz of the Catalan Institution for Research and Advanced Studies cyclized (J. Am. Chem. Soc. 2012, 134, 15505. DOI: 10.1021/ja306211q) the terminal alkyne 13 directly to the cyclopentene 15. Olivier Baudoin of UniversitÚ Claude Bernard Lyon 1 closed (Angew. Chem. Int. Ed. 2012, 51, 10399. DOI: 10.1002/anie.201205403) the pyrrolidine ring of 17 by selective activation of a methyl C-H of 16. Jeremy A. May of the University of Houston found (J. Am. Chem. Soc. 2012, 134, 17877. DOI: 10.1021/ja308305z) that the Rh carbene derived from 18 inserted into the distal alkyne to give a new Rh carbene 19, that in turn inserted into a C-H bond adjacent to the ether oxygen, to give 20.

Gui-Rong Qu and Hai-Ming Guo of Henan Normal University oxidized (Org. Lett. 2012, 14, 5546. DOI: 10.1021/ol302640e) 22 in cyclohexane, forming the new carbon-carbon bond of 23. Irena S. Akhrem of the A. N. Nesmayanov Institute of Organoelement Compounds carbonylated (Tetrahedron Lett. 2012, 53, 4221. DOI: 10.1016/j.tetlet.2012.05.164) 24 to give the ester 25. Professor Baudoin developed (Angew. Chem. Int. Ed. 2012, 51, 10808. DOI: 10.1002/anie.201206237) a protocol for walking an organopalladium intermediate along a straight chain, leading to the methyl coupled product 28. Jin-Quan Yu of Scripps/La Jolla overcame (J. Am. Chem. Soc. 2012, 134, 18570. DOI: 10.1021/ja309325e) the inherent preference for methyl functionalization, converting 29 selectively to 31.

There has been a great deal of work (see C-H Functionalization 2012, September 17) on the functionalization of a C-H bond adjacent to an N. For the most part, such reactions are based on initial oxidation at the nitrogen center. These reactions are now well enough known that they will no longer be covered under this C-H Functionalization topic.

D. F. Taber, Org. Chem. Highlights 2013, September 16.