Transition metal mediated synthesis of heterocycles via carbon-hydrogen bond activation

Dicobalt octacarbonyl was found to be an efficient catalyst for the selective conversion of diallylanilines to quinolines in good yields under mild conditions in the presence of one atmosphere of carbon monoxide. The reactions were very clean and the only byproducts were the corresponding anilines. The reaction scope and the regioselectivity of diallylanilines were examined by a series of electron donating and electron withdrawing functional groups at ortho- and para-positions of the diallylanilines. The results show that both steric and electronic effects influence the isolated yields. Electron withdrawing groups inhibit the reaction. Solvent effects, temperature effects, as well as catalyst loadings have also been investigated. It was found that no obvious solvent effects have been observed. A small catalyst loading can catalyze the reaction despite long reaction times.;Based on the experimental results, some isotopic labeling experiments have been devised to try to elucidate the mechanism. The results for the reaction of partially deuterated diallylaniline showed that one of the ortho C--D bonds was activated and the deuterium was selectively transferred to the methylene position of the 2-ethyl group of the 2-ethyl-3-methylquinoline. The position to which the deuterium was transferred was not expected. Initially, no mechanism could be proposed to explain how deuterium would be shifted to this position. A large ME of 5.4(1) was obtained by the reaction of a mixture of partially deuterated diallylaniline-d5 and nondeuterated diallylaniline-d 0. Furthermore, some isotopic experiments with the observed intermediate allylcobalttricarbonyl have been investigated. Based upon the isotopic preference for deuterium on carbon to account for the location of deuterium in the quinoline product, a new pathway is proposed in the absence of any observable intermediates.;Bi-, tri-, and tetra-cyclic isoquinoline salts were readily synthesized in excellent yields at room temperature from easily available starting materials after three reaction steps. Aromatic C--H activation was first promoted by sodium acetate with [Cp*MCl2]2 (M = Rh, Ir) at room temperature to form cyclometallated compounds. Dimethylacetylenedicarboxylate was then found to insert into the metal-carbon bonds of the cyclometallated compounds. Finally the insertion compounds underwent oxidative coupling to obtain the desired isoquinoline salts as well as regeneration of [Cp*MCl2] 2. Moreover, it is possible to synthesize the isoquinoline salts in one pot procedures from easily available starting materials, and provides a novel efficient way for the metal-mediated synthesis of heterocycles.;The sodium acetate-promoted C--H activation in a series of para-substituted phenyl imines has been examined using [Cp*MCl 2]2 (M = Ir, Rh). The regioselectivity was investigated using a series of meta-substituted phenyl imines (-OMe,-CH 3, -F, -COOMe, -CF3, and -CN) and 2-phenylpyridines (-OMe, -CH3, and -CF3). It was found that substrates with electron-donating substituents react much faster than substrates with electron-withdrawing substituents, which is consistent with an electrophilic C--H activation mechanism. It was also found that the regioselectivity of the C--H activation was extremely sensitive to steric effects, with a meta-methyl group leading to only one regioisomer. Solvent and temperature studies showed that the reaction rate could be dramatically increased both by increasing temperature and by using polar solvents such as methanol. The regioselectivity was solvent dependent for the reaction with [Cp*IrCl2]2, but independent of solvent for the reaction with [Cp*RhCl2] 2. The regioselectivity was temperature independent for both metals. With added acid (HOAc, HCl), the aromatic C--H activation was shown to be reversible. Kinetic studies were performed, leading to the conclusion that [Cp*M(OAc)]+ is the key catalytic species responsible for the electrophilic C--H activation.;Reactivity of four different cyclometallated iridium and rhodium complexes with ancillary ligands with different electronic and steric properties has been investigated by reactions of ethylene, propylene, carbon monoxide, tert-butylisocyanaide, acetylene, and phenylacetylene. The results were varied, producing different metallacycles. The regioselectivity was also investigated for each cyclometallated complex by using a series of internal unsymmetrical alkynes, and the results revealed that the regioselectivity was controlled by both steric and electronic factors.