Theoretical Study Of Transition-metal Promoted Carbon-Carbon Construction Reactions

The carbon–carbon bond is the most widespread and fundamental bond existing in organic compounds.Carbon–carbon bond construction constitutes the central event in organic synthesis.Classic carbon–carbon bond construction reactions such as Diels-Alder and Witting reactions have played an important role in organic synthesis since their discoveries.During the past decades,transition-metal promoted carbon–carbon bond construction reactions have been one of the most important tools in organic synthesis.Owing to the tremendous advances of theoretical chemistry,computational chemistry is increasingly employed to study the experimental results,explain the mechanism and predict reactivities.In this paper,theoretical calculation was employed to study the mechanism of transition-metal promoted carbon–carbon construction reactions.This paper mainly includes the following three parts:1.The B3 LYP and M11 DFT method were used to study iron promoted cyclization of isonitrile with aldehyde to construct carbon–carbon bond.Theoretical calculation was employed to study the mechanism of the reaction and the electronic effect of substituents.Computational results suggest that the radical transfer process between butyloxycarbonyl radical and benzaldehyde is the rate-determining step.Subsequent nucleophilic addition of acyl radical towards cyano group and the radical cyclization step are facile processes.Besides,the electronic effect of substituents on different sites was also investigated using the Hammett plot.The obtained results indicate that,the electron-withdrawing group on para-position of cyano group would facilitate the nucleophilic addition of acyl radical,and the electron-donating group on para-position of acyl group would promote the radical cyclization step.2.DFT methods B3 LYP and M11-L were engaged to study the mechanism of palladium/copper-catalyzed C8–H bond activation of naphthalen-1-amine to construct carbon–carbon bond.We proposed two possible reaction pathways.One pathway consists of carbonyl insertion,C8–H bond or C2–H bond activation and reductive elimination of C–C bond.Another pathway includes C–H bond activation,carbonyl insertion to C-Pd bond and reductive elimination of C–N bond or carbonyl insertion to N–Pd bond and reductive elimination of C–C bond.Computational results suggested the reaction underwent carbonyl insertion,C8–H bond activation and reductive elimination of C–C bond.The calculated results are in good agreement with the experimental results.3.B3 LYP and B3LYP-D3 DFT were engaged to study the mechanism of reductive elimination from diarylgold(III)complexes to construct carbon–carbon bond.First,a series of diarylgold(III)compounds with substituents were designed and validated their energy barriers of reductive elimination by theoretical calculations.On the basis of the theoretical study above,a series of stable fluorine substituted diarylgold(III)complexes cis-[Au(L)(Ar)(Ar')(Cl)] were synthesized for the investigation of gold(III)intermediates.The bond length and bond angle of the complexes were calculated.The detailed reaction mechanism was investigated,in which the direct reductive elimination is the possible pathway for the C-C bond construction rather than dissociation of phosphine ligand or chloride.The calculation results also show that the activation energy could be decreased by engaging larger ligands,which will lead to a fast rate and mild reaction condition.