Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 22, 2008
Douglass F. Taber
University of Delaware

Intermolecular and Intramolecular C-H Functionalization

Peter Legzdins of the University of British Columbia has described (J. Am. Chem. Soc. 2007, 129, 5372. DOI: 10.1021/ja0713633) a stoichiometric tungsten complex that specifically functionalized the primary H of an alkane 1 to give the organometallic 2. Neither the scope of the reactivity of 2 nor the functional group compatibility of this process have as yet been explored.

Ruggero Curci of the Universitŕ di Bari has reported (Tetrahedron Lett. 2007, 48, 3575. DOI: 10.1016/j.tetlet.2007.03.101) the stereospecific hydroxylation of 1,3-dimethyl cyclohexane 4 to the diol 6. Yasuyuki Kita of Osaka University has developed (Org. Lett. 2007, 9, 3129. DOI: 10.1021/ol071315n) conditions for specific benzylic oxidation, converting 7 into 8 with high diastereocontrol. Larry E. Overman of the University of California, Irvine has established (Org. Lett. 2007, 9, 5267. DOI: 10.1021/ol702518t) that by using a slow H-atom donor, it was possible to effect intramolecular H abstraction, leading, by oxidation of the intermediate captodatively-stabilized radical, from 9 to the acetate 10.

The target C-H of 9 is activated by being adjacent to the ring nitrogen. There are many other ways that nitrogen, easily oxidized, has been used to activate a C-H for bond formation. Takehiko Yoshimitsu and Tetsuaki Tanaka of Osaka University have established (Org. Lett. 2007, 9, 5115. DOI: 10.1021/ol7023295) a free-radical route for the homologation of a tertiary amine such as 11 with phenyl isocyanate 12. Chuan He of the University of Chicago has devised (Angew. Chem. Int. Ed. 2007, 46, 5184. DOI: 10.1002/anie.200700760) an Ag catalyst for the oxidative cyclization of sulfamates such as 15. M. Christina White of the University of Illinois has developed (J. Am. Chem. Soc. 2007, 129, 7274. DOI: 10.1021/ja071905g) a ligand system that allows the diastereoselective Pd-mediated allylic oxidation of 16 to 17.

The cyclization of 18 to 19 developed (J. Org. Chem. 2007, 72, 8994. DOI: 10.1021/jo7016982) by Renhua Fan of Fudan University is thought to be proceeding via H atom abstraction by an intermediate nitrogen radical. The oxidation of the amine 20 to the endocyclic enamine 21 reported (J. Am. Chem. Soc. 2007, 129, 14544. DOI: 10.1021/ja075694r) by Maurice Brookhart of the University of North Carolina depended on the ease of oxidative addition of an intermediate alkenyl Co complex into the C-H bond adjacent to the nitrogen. The multistep cyclization of 22 to 23 devised (Org. Lett. 2007, 9, 4375. DOI: 10.1021/ol702017t) by Philippe Renaud of the Universität Bern depended on the ease of H atom abstraction adjacent to nitrogen.

Carbon-carbon bonds can also be established by C-H functionalization. Justin Du Bois of Stanford University has shown (Org. Lett. 2007, 9, 4363. DOI: 10.1021/ol701950d) that sulfonates such as 24 can be cyclized to the sultone with high diastereocontrol. Kálmán J. Szabó of Stockholm University has found (Angew. Chem. Int. Ed. 2007, 46, 6891. DOI: 10.1002/anie.200702499) that depending on conditions, either the alkenyl (illustrated) or the allylic C-H of a cycloalkene such as 27 can be activated for bond formation. Maurizio Fagnoni of the University of Pavia has delineated conditions (Angew. Chem. Int. Ed. 2007, 46, 6495. DOI: 10.1002/anie.200701462) for direct biphenyl formation from easily oxidized aromatics such as 31 bearing leaving groups. Gerhard Hilt of the Philipps-Universität Marburg has established (Angew. Chem. Int. Ed. 2007, 46, 8500. DOI: 10.1002/anie.200703180) a Co catalyst for the efficient Alder ene homologation of a terminal alkene 34 to the unsaturated ester 36.

D. F. Taber, Org. Chem. Highlights 2008, September 22.