Studies On Palladium-catalyzed Coupling Reaction With Alkynyl Halides

Palladium-catalyzed coupling reactions have been recognized as one of the most powerful protocols for constructing of carbon-carbon bonds and carbon-heteroatom bonds in organic chemistry. In this dissertation, we wish to report several efficient methodologies to generate carbon-carbon bonds by the Pd-catalyzed cross-coupling reactions of alkynyl halides. The main contents and results are listed as following:1. Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction of Alkynyl Halides with Organoboronic AcidsA novel, mild palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of alkynyl halides with organoboronic acids under aerobic conditions has been developed. In the presence of bis(dibenzylideneacetone)palladium(0),cesium carbonate and methanol, a variety of alkynyl halides(I, Br and Cl)underwent the cross-coupling reaction with organoboronic acids affording the corresponding unsymmetrical diarylalkynes in moderate to good yields at room temperature. Importantly, the halogen atoms(Br, I) can be tolerated in this protocol, thereby facilitating additional modifications at the halogenated positions. It is noteworthy that the reaction of alkynyl chlorides with arylboronic acids was firstly reported. The method provides an effective complement for traditional Suzuki-Miyaura cross-coupling reaction and Sonogashira cross-coupling reaction.In order to explore the applicability of the methodology, 3-iodo-Nmethyl-N-phenylpropiolamide was choosed to react with(4-iodophenyl)boronic acid and 1-phenylethyne. To our delight, a diacetylene compound,which is a very useful pharmaceutical intermediate was obtained after two steps: 3-(4-iodophenyl)-N-methyl-N-phenylpropiolamide was obtained firstly under the optimal conditions, and then underwent a Sonogashira coupling reaction with 1-phenylethyne by functionalization of the iodine group. Further more, 9-phenyl-3a, 4-dihydronaphtho [2, 3-c]furan-1(3H)-one, which is a very important lignan, can also be readily prepared under very mild reaction conditions by the palladium-catalyzed cross-coupling of cinnamyl 3-iodopropiolate and organoboronics, followed by cyclization using BEMP as catalyst.These results make the methodology more useful in pharmaceutical chemistry.2. Palladium-Catalyzed Cross-Coupling Reaction of 3-Iodopropynamides with Alcohols for Constructing Carbon-Oxygen BondA novel and selective method for the synthesis of carbamoylacetates via the alcoholysis of 3-iodopropynamides has been developed. 3-Iodopropynamides react with alcohols in the presence of palladium(II) acetate and 1, 4-diazabicyclo[2.2.2]octane(DABCO) to afford the corresponding carbamoylacetates in moderate to good yields. Notably, the reaction is conducted at room temperature, aerobic conditions, and has a high selectivity and satisfactory yield. The method provides an effective complement for traditional methods for construction of carbamoylacetates. A plausible reaction mechanism is proposed based on the experimental observations.3. Palladium-Catalyzed Hiyama Cross-Coupling Reaction of Alkynyl Halides with AryltrialkoxysilanesA simple, mild palladium-catalyzed Hiyama cross-coupling reaction of alkynyl halides with aryltrialkoxysilanes has been developed. In the presence of bis(dibenzylideneacetone)palladium, silver fluoride and acetonitrile, a variety of alkynyl halides(I, Br and Cl), whether electron-deficient or electron-rich, underwent the cross-coupling reaction with aryltrialkoxysilanes at room temperature to afford the corresponding alkynes in moderate to good yields. Notably, the reaction is conducted at room temperature and aerobic conditions. Meanwhile, the cross-coupling reaction of alkynye with aryltrialkoxysilanes were less effective than corresponding alkynyl halides in terms of yields. No cross-coupling product was generated in the control experiment with terminal aliphatic alkyne while bromoalkynes are also suitable substrates leading to the desired products smoothly in moderate yields.