Intermolecular and Intramolecular C-H Functionalization

Peter Legzdins of the University of British Columbia has described (J. Am. Chem. Soc. 2007, 129, 5372. DOI) 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 Università di Bari has reported (Tetrahedron Lett. 2007, 48, 3575. DOI) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) 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) a Co catalyst for the efficient Alder ene homologation of a terminal alkene 34 to the unsaturated ester 36.

Books written by Highlight Authors:

Douglass F. Taber

C. Oliver Kappe