Highly Enantioselective Rhodium-catallyzed Cross-addition Of Silylacetylenes To Cyclohexadienone-tethered Internal Alkynes

In modern organic synthesis,the carbon-carbon triple bond is a very important and practical structure unit,with structural versatile reaction activities.For example,through hydration,hydrogenation,hydroboration,and click reactions,the alkynyl group can be easily converted into carbonyl,alkyl,alkenyl,and heteroaryl groups.Therefore,a variety of chiral compounds will be obtained by combining various reactions that can occur with a series of stereocenters constructed from alkynyl groups.Moreover the hydroacetylation of terminal alkynes with unsaturated compounds catalyzed by transition-metal has been widely investigated,and become an efficient,attractive and atom-economical tool to introduce alkyne moiety.In the first part of the thesis,the reaction of a rhodium-catalyzed cross-addition of silylacetylenes to cyclohexadienone-tethered internal alkynes was systematically studied.The reaction was conducted by using the metal complex bis?norbornadiene?rhodium tetrafluoroborate?Rh?nbd?₂BF₄?and the ligand?R?-SEGPHOS as catalyst species.And triisopropylsilylacetylene,Cs₂CO₃ and toluene were applied as the alkyne source,base and solvent for investigation.The reaction can be carried out at80°C for 5 h,and the alkynylative cyclization product containing the cis-hydrobenzofuran skeleton can be obtained with good yields?up to 88%?and excellent enantioselectivities?up to 96%?.A total of 28 substrates in the cyclohexadienone-tethered internal alkynes could be well tolerated and the reactions proceeded smoothly with good yield.Among them,as for estrone derivated substrate showed that the stereochemistry of the product was completely controlled by the ligand.Firstly,Triisopropylsilylacetylene forms alkynyl rhodium intermediate by the activation of the base.Then,the alkynyl rhodium intermediate,which undergo regioselective cross-addition with alkynes of 1,6-enynes,afforded alkenyl rhodium species.Subsequently the alkenyl rhodium species enantioselective conjugated addition with enones under a ligand afforded the desired alkynylative cyclization product.The silylacetylene on the product can be subjected to versatile synthetic conversion.For example,desilylation of the silylacetylene with tetrabutylammonium fluoride?TBAF?afforded the terminal alkyne,and Sonogashira coupling of the terminal alkyne with 1-bromo-4-iodobenzene proceeded smoothly to form the aryl-substituted internal alkyne.The triazole product could be easily obtained through a copper-catalyzed click reaction between the terminal alkyne and benzyl azide.Moreover,the terminal alkyne could undergo silver-mediated bromination to afford the alkynyl bromine product in high yield.To demonstrate the synthetic utility of this rhodium-catalyzed alkynylative cyclization reaction,a gram-scale experiment was carried out,and the corresponding cyclization product was isolated with good yield and constant enantioselectivity.We have developed the first highly chemo-,regio-,and enantioselective rhodium-catalyzed alkynylation/intramolecular conjugate addition tandem reaction between terminal silylacetylenes and cyclohexadienone-tethered internal alkynes.This tandem process showed perfect atom-economy,broad functional group tolerance and could conveniently afford optically pure cis-hydrobenzofuran skeletons containing a versatile silylacetylene fragment.The cis-hydrobenzofuran skeletons are widely present in pharmaceutical and biologically active molecules,and our reaction provides a new approach to the synthesis and post-modification of such framework compounds.The second part introduces the work of the rhodium-catalyzed of terminal alkynes hydroarylation.We have developed a novel Cp*Rh?III?-catalyzed,redox-neutral hydroarylation of terminal alkynes under mild condition by using the AcOH as the solvent.This reaction offers an effective approach for the synthesis of alkenylated heterocycles with excellent yield?50%-99%?,broad substrate scope?37 examples?and good functional group compatibility.Also,in this transformation,the amount of alkynes can be reduced to 1.2 equivalents,which indicates the AcOH may play significant role in this reaction.