Pd-Catalyzed Enantioselective Ring-Forming/Ring-Opening Cross Coupling Reactions Of Unactivated Olefins With Benzocyclobutenols

Pd-catalyzed C-C cross-coupling reactions have become indispensable methods in modern organic synthesis.Transition-metal-catalyzed asymmetric intramolecular cyclization of unactivated alkenes,a kind of ring forming reactions,have emerged as a powerful and straightforward protocols to chiral cyclic compounds containing quaternary stereocenters.On the other hand,transition-metal-catalyzed C-C bonds activation represents straightforward synthetic protocol to construct carbon frameworks that are difficult to synthesize by conventional methods.In this thesis,Pd-catalyzed enantioselective ring-forming/ring-opening cross coupling reaction has been developed with diverse aryl halides-tethered alkenes and benzocyclobutenols as substrates,which renders the highly enantioselective diarylation of unactivated alkenes and enables the rapid access to chiral 2,3-dihydrobenzofurans bearing a quaternary stereocenter.In the first part,transition-metal-catalyzed asymmetric intramolecular cyclization of unactivated alkenes has been described.Meanwhile,the ring opening reactions of benzocyclobutenols and cyclobutanols based on transition-metal-catalyzed C-C bond activation has also been reviewed.In the second part,we investigated feasibility of the Pd-catalyzed ring-forming/ring-opening cross coupling reactions with readily available aryl halides tethered alkenes and benzocyclobutenols as substrates.Allyl ether la,derived from o-iodophenol,and benzocyclobutenols 2a were selected as the model substrates for reaction condition optimization.The conditions of the reaction are screened inluding chiral ligands,palladium source,bases,anhydrous solvent,reaction temperature and time,etc.The optimal reaction condition were as follows:under nitrogen,5 mol%of Pd(AllyI)Cp as a source of palladium,with 10 mol%of L68 as ligand,Cs2CO3 as base,anhydrous toluene(1 mL)65℃,13 hours.with 85%yield and 95%ee is worth to the desired target compounds.Then,30 central chiral biaryl compounds were synthesized with medium yield and good Ee value by expanding the substrate of o-iodoallyl ether and phenylcyclobutenol derivatives,and the target products were characterized by 1HNMR,13CNMR,HPLC,etc.