Study On DDQ-mediated Cross Coupling Reactions Between Cyclic Acetals With Oxygen-based Nucleophiles

With the booming of green chemistry and atom economy concept, it has become a hot research topic to build a novel C-C bond or C-X bond by activating C-H bond of different reaction’s substrates under oxidative condition. Comparing with the metal-catalyzed cross-dehydrogenative coupling reactions, metal-free coupling reactions are greener and more advantageous. Therefore, we have focused on the oxidative cross-coupling reaction via C-H bond activation without any metal catalyst.Our group has made progress on the research of DDQ-promoted activation of acetophenones sp3C-H bonds. As a continuing part, this thesis would concentrate on the systematic exploration of the CDC reaction of cyclic acetals with oxygen-based nucleophiles in the presence of DDQ. Specific contents were as follows:Firstly, DDQ-promoted C-O formation between cyclic acetals and carboxylic acids was studied. With the beginning,2-phenyl acetal reacts with benzoic acid in the presence of DDQ as a model reaction, to obtain the optimal reaction conditions. After screening, experimental results showed that the highest yield(90%) could be achieved in the optimal condition such as dichloromethane as solvent, the material ratio was acetal/carboxylic acid/DDQ ratio being 2/1/1.2 for 12 hours in sealed tube at 80℃. Then under the optimal reaction conditions, several kinds of cyclic acetals and various benzoic acids or phenylacetic acids were applied to obtain 21 corresponding carboxylic acid ester compounds in the yields of 43%-94%. Much to our surprise, the same esters were observed when phenylacetic acids replaced corresponding benzoic acids. Based on the reaction results when different substrates were used, the electronic steric effects of substituents on the rings were discussed, and the possible reaction mechanism was proposed.Secondly, DDQ-promoted CDC reaction between cyclic acetals and simple ketones was studied. With the beginning,2-phenyl acetal reacts with acetophenone in the presence of DDQ as a model reaction, to obtain the optimal reaction conditions. After screening, experimental results showed that the highest yield(61%) could be achieved in the optimal condition such as the material ratio was acetal/acetophenone/DDQ ratio being 1/5/2.4, solvent-free reaction at 100℃. Under the optimal reaction conditions, several kinds of cyclic acetals and various methyl ketones were applied to obtain 11 corresponding three molecular series products in the yields of 31%～64%.It was reported for the first time that a novel domino CDC reaction of acetals with methyl ketones by sp3 C-H activation using DDQ as the oxidant and reactant precursor. It allows the incorporation of DDQ as molecular moiety into the final product. Finally, the possible reaction mechanism was proposed.Lastly, the coupling reaction of DDQ with cyclic acetals was studied. The experimental results showed that DDQ was used not only as the oxidant but also as the reactant precursor, 2equiv. DDQ and lequiv. cyclic acetal incorporated into a three molecular compound by the cross-coupling reaction. In this thesis, the optimized conditions were obtained in the same way and four corresponding products were obtained.In conclusion the three CDC reactions of cyclic acetals with oxygen-based nucleophiles has been demonstrated. Compared with the traditional synthetic methods, our methods developed in this thesis feature easy operation, short synthetic steps, and mild reaction conditions.