Carbon-hydrogen bonds remote functionalization

Since the observation that Rh(II) carboxylates are superior catalysts for the generation of transient electrophilic metal carbenoids from a-diazocar-bonyls compounds, intramolecular carbenoid insertion reactions have assumed strategic importance for C-C bond construction in organic synthesis [1]. Rhodium(ll) compounds catalyze the remote functionalization of carbon-hydrogen bonds to form carbon-carbon bonds with good yield and selectivity. These reactions have been particularly useful in the intramolecular sense to produce preferentially five-membered rings. 

The remote functionalization of carbon-hydrogen bonds by a-diazoketones according to the general eq. (1) is efficiently catalyzed by rhodium(II) complexes and yields cyclopentanones, lactams, and lactones, depending on the substituent Y [3, 4]. Typical reaction conditions are boiling methylene chloride or boiling... 

The activation of intramolecular carbon-hydrogen bonds by metal ions in the gas phase first involves tt-coordination, followed by remote functionalization of C—H or C—C several carbons distant from the initial coordination site. Schwarz has reviewed his prolithic work in this area. High-resolution translational energy loss measurements on the remote functionalization of internal alkynes by Cr" have been made. These indicate that the ions involved are in the ground state and that no added collisional energy transfer is needed for cyclometallation to proceed. The reactions of Fe", Co", and/or Ni" have been studied with alkyl-substituted amines, " alcohols, ketones, nitriles, " ... 

Electrophilic fluorination by substitution of hydrogen at unactivated tertiary carbon has been achieved by use of either CF3OF or elementary fluorine (diluted with N2). Electron-attracting substituents direct the reaction to remote C—H bonds, suggesting that the reaction has electrophilic rather than free-radical character. Examples include the 9a-fluorination of 5a-androstane-3/8,17/8-diol esters (309), 14a-fluorination of various 5a,6j8-dichloro-3,17-disubstituted steroids of type (310), and 17a-fluorination of 5a-cholestan-3j8-yl esters or their 5a,6/8-dichloro-derivatives. Hypobromite and other hypohalite reactions for the functionalization of unactivated carbon atoms are reviewed. ... 

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