Theoretical Study On The Mechanism And Chemoselectivity Of Gold-catalyzed Propargyl Esters Cascade Cyclization

Cascade reaction is a significant type reaction for material chemistry,pharmaceutical chemistry,organic synthesis and catalytic chemistry.Among them the gold-catalyzed cycloisomerization of propargyl esters is a popular reaction in the research fields.Besides,propargyl ester is a very important substrate.In the Au catalysts,propargyl esters occurred tandem reaction can afford carbocyclic,heterocyclic,aromatic and acyclic compounds.In this study,we optimize all structures in reaction processand calculate potential energy surface using density functional theory.Based on molecular orbital,transition theory,quantum chemistry and the natural bond orbital,the reaction mechanism and chemoselectivity of gold-catalyzed propargyl esters cascade cyclization have been explained by the obtained thermodynamic data,structural parameters,orbital's energy.Our researches provide useful insights for organic synthesis designing,catalyst choosing and experimental conditions screening.The whole paper consists of four sections.Chapter ?.First,we introduced the progress of reaction for gold-catalyzed.Second,mainly review the gold catalyst's species and catalytic activity.Finally,review the reaction typeof alkyl and our work.Chapter ?.Summarizes the theory of quantum chemistry and calculation methods in our's paper.Chapter ?.The present study reports a detailed theoretical analysis of the mechanistic features in the 1,6-diyne ester cycloisomerization,the chemoselectivity of which is driven by the nature of gold(I/III)catalyst.The DFT calculations reveal that the Au(I)and Au(III)catalysts {[AuI(PPhMe2)(NCMe)]+,AuICl,and [AuIII(Cl)2(Pic)](Pic =2-picolinate)} entail similar 1,3-acyloxy migration and 5-exo-dig cyclization steps,whereas completely distinct reaction pathways are observed after the formation of the putative vinyl gold complex intermediates.In the [AuI(PPhMe2)(NCMe)]+-catalyzed process,such an intermediate undergoes the Friedel-Crafts-type reaction to afford 1H-cyclopenta[b]naphthalene along with the protodeauration and hydrogen shift.In contrast,in the transformation catalyzed by AuICl or [AuIII(Cl)2(pic)],a putative vinyl gold complex intermediate endures the rotation of the oxonium moiety to generate a new intermediate which then undergoes the 1,5-carbonyl migration to furnish cis-cyclopenten-2-yl ?-diketone.The obtained theoretical data are in a very good agreement with the experimental evidence,suggesting that the inherent differences of electronic and steric properties between the Au(I)and Au(III)complexes,used as catalysts in the 1,6-diyne ester cycloisomerization,determine the type of the final product.Chapter ?.This study reports a detailed theoretical analysis of the mechanisms and chemoselectivity for the formation of benzo[b]fluorenes orbenzofulvenes from propargyl esterscatalyzed by an organometallic Au(I)complex.Three different substitution patternswithin the1,5-diyne ester substrateswere explored to rationalize the reaction mechanism and chemoselectivity.DFT calculationsrevealthat the titlereaction proceeds through four main steps:(i)1,3-acyl-shift,(ii)6-endo-dig or 5-exo-dig cyclization,(iii)Friedel-Crafts-type,and(iv)proton transfer,with the step(ii)being the rate-determining in all studied pathways.In the absence of substituentsat the aromatic rings of the substrate(R = H),the 6-endo-dig cyclization is favored.In turn,in the presence of one strong electron-donating substituent at the backbone(R = OCH3)of the substrate,the 5-exo-digcyclizationis favored.Besides,a modification of the substrate's acetyl group by a pivaloyl group leads to an activation barrier difference between the6-endo-dig and 5-exo-digcyclizations,which increases and suppresses the formation of benzofulvenes.The obtained theoretical data are in a very good agreement with apriorexperimental evidence,suggesting that the substituent plays a crucial role in the outcome of the final product.A high chemoselectivity can be explained by the hindrance(torsional strain)along the forming C–C bond and the carbocation stability provided by substituents.