Studies On C-H Activation-Based Domino Reaction By Palladium-Catalyzed And Synthesis Of Small Cycle Compounds

The construction of the C-C and C-X bonds is the center of synthetic organic chemistry. The explosive development of C-H activation and domino reaction in recent decades, which both afforded more abundant ways to install C-C and C-X bonds and well responsed to the appeal for the atom economy and "green chemistry" from community and industry. Based on the idea of green chemistry, our researchs focused on the synthesis of small cycle compounds, via a domino process with the combination of Heck reaction/C-H activation/cyclization reactions, from substrates of bromides and norbornenes, and catalyzed by Pd(0). The thesis consists mainly of four parts as follows:1. Pd(0)-catalyzed methylene-and methyl-cyclopropanation via C(sp2)-H activationWe developed Pd(0)-catalyzed methylenecyclopropanation and methylcyclopropanation reactions via combination of Heck-type reaction and C(sp2)-H activation.-Catalyzed by Pd(OAc)2/PPh3in toluene at110℃,β-bromostyrenes reacted with norbornenes, the formed intermediates norbornenylpalladium complexes tend to further undergo C(sp2)-H activation, not just one-step Heck reaction via β-H elimination, owing to the strain of norbornenes. For the further C(sp2)-H activation, there are two choices between the benzene hydrogen and the vinyl hydrogen. The regioselectivity prefered to the latter under our reaction conditions, and an intermediate containing cyclopropane-ring palladium complex was formed. y-H elimination of the palladium complex gave methylenecyclopropane derivatives in the presence of K2CO3. Bromostyrenes, bromovinylheteroarenes and chain vinylbromides as well as Z and E-alkenes all are suitable for the domino processes. The electron-donating group on benzene improved the yields of the products, the ortho-substituent reduced the yields due to the steric-hinerance effect. For the chain vinylbromides, the reductive elimination took place on the5-H, not y-H, leading to vinylidenecyclopropane derivatives. However, the y-H elimination of the reaction was not occurred in the presence of CH3ONa as the base when we screened the reaction conditions for better yields. The padallium complex containing cyclopropane skeleton grabed a proton from the reaction system to produce methylcyclopropanes when CH3ONa/CH3OH was used. This result was unexcepted and never reported. Hence, we preliminary studied the mechanism using the isotope tracer technique. Ds-toluene, CD3OD and CD3OH were respectively employed as solvent and additive to carry out the experiment, the results showed that the proton was from CH3OH.2. Pd(0)-catalyzed bismethylenecyclobutanation via twofold C(sp2)-H activation In this section, We developed a Pd(0)-catalyzed bismethylenecyclobutanation reaction via a combination of Heck-type reaction, C(sp2)-H activation and Heck-type reaction, In the presence of Cs2CO3and catalyzed by Pd(OAc)2/PPh3in toluene at110℃, the reaction of (Z)-β-bromostyrenes and norbornenes formed norbornenylpalladium complexes that could not underg β-H elimination but tend to perform C(sp2)-H activation on the vinyl to form a four-membered palladiumcycle complex. The palladiumcycle intermediate was further oxidated by another β-bromostyrene to form PdⅣ complex, its selective reductive elimination was followed by intramolecular C(sp2)-H activation leading to a bismethylenecyclopentapalladium intermediate, which underwent reductive elimination to give bismethylenecyclobutane derivatives. The arylbromides containing electron-withdrawing group in benzene ring afforded the better yields, it is possibly because that the second oxidative addition of a palladium(II) species into bromostyrene containing electron-withdrawing group is more easer than that of electron-donating one. The reaction of arylbromides containing the ortho-substituent did not work due to steric-hinerance effect.3. Pd(0)-catalyzed cyclopropanation via C(sp2)-H activationWe developed a Pd(0)-catalyzed cyclopropanation via a combination of Heck-type reaction and C(sp3)-H activation. Catalyzed by Pd(OAc)2/PPh3in toluene at100℃, β-Bromostyrenes reacted with norbornenes, the formed norbornenylpalladium complexes tend to perform C-H activation owing to the strain of norbornenes hindering its elimination of β-H. There are two choices between C(sp2)-H activation of benzene ring and C(sp3)-H activation of the methylene, the regioselectivity of C-H activation prefered to the latter under our reaction conditions due to the different transition states. So cyclopropane skeleton was installed. DFT calculations showed that the transition state of C(sp3)-H activation is more stable than that of C(sp2)-H activation with a significant energy advantage of over6kcal/mol-1, so C(sp3)-H activation was favoured.4. Pd(0)-catalyzed synthesis of ene-ynes via C(sp2)-H activation We developed a Pd(0)-catalyzed synthesis of ene-ynes via a combination of double Heck-type reaction and C(sp2)-H activation. In DMF at110℃and catalyzed by Pd(OAc)2/PPh3, the reaction of β-bromostyrenes with norbornenes formed1,5-ene-yne. The product may resulted from the fact that the formed norbornenylpalladium complexes could not undergo β-H elimination in the presence of Cs2CO3and DMF, but tend to perform C(sp2)-H activation on the vinyl and formed a five-membered palladiumcycle complex, which was further oxidated by another vinyl bromide to form a PdⅣ complex. The domino reductive elimination of the PdⅣ complex lead to1,5-ene-yne.