Synthesis Of Functionalized Binaphthyl Compounds Via Arylation Or Rearrangement Reactions

Biaryl atropisomers constitute the core structure of a wide range of natural biologically active molecules,such as vancomycin,which is a good antibiotic for bacterial infections.1,1?-bi-2-naphthol(BINOL),2-amino-2?-hydroxy-1,1?-binaphthyl(NOBIN)and 1,1?-binaphthyl-2,2?-diamine(BINAM)represent the privileged skeleton of many biaryl compounds,which are widely used in asymmetric catalysis as chiral ligands or catalysts.The application of biaryls in the field of materials science such as fluorescent sensors,host-guest chemistry,optical switches,molecular machines,and liquid crystals further illustrates their importance.Therefore,the efficient construction of biaryl frameworks has wide interests and remains great challenges in organic synthesis,pharmaceutical chemistry and material science.The synthesis of biaryl compounds has been developed rapidly,but there are still some problems and deficiencies,such as poor chemical selectivity in cross-coupling reactions,relatively single reaction mode,difficulties in substrate synthesis,etc.The direct coupling of two aryl components to form a chiral axis would be one of the most effective and direct stragies for the synthesis of such chiral biaryls.In this thesis,highly selective C-H arylation and domino rearrangement reactions have been developed to directly construct chiral axis,thereby obtaining functionalized biaryls.Highly selective C-H arylation of 2-naphthols or 2-naphthylamines with 1-diazo-2-naphthoquinone were achieved with palladium acetate as the catalyst.Under mild conditions,1,1'-bi-2-naphthols and the derivatives of2-amino-2'-hydroxy-1,1'-binaphthyl were achieved with up to 98% and up to 77% yield,respectively.Both types of biaryls can be prepared on a gram scale,and the yields almost remain the same.The asymmetric transformation of 2-naphthol was attempted using palladium-binding chiral ligands or chiral phosphoric acid as the catalyst,and the corresponding products were obtained in 58% yield with 60% enantioselectivity.Domino arylation and regioselective sigmatropic rearrangement reactions of aryl hydroxylamines with diarylhalonium salts directly using sodium carbonate as the base were realized in the absence of any transition metals.Under the mild conditions,2-amino-2'-hydroxy-1,1'-binaphthalene and arylated2-amino-2'-hydroxy-1,1'-binaphthalene were synthesized with up to 94% and up to 95%yield,respectively.The gram-scale preparation can also be achieved,and the yields almost remain the same.The arylation process maybe undergo ligand coupling mechanism under alkaline conditions,whereas without benzyne and free radical pathway.Afterwards,it undergoes an uninterrupted process of [1,3]-migration,[3,3]-rearrangement and rearomatization to obtain the target product.Two enantiomers of optically pure 2-amino-2'-hydroxy-1,1'-binaphthalene were obtained based on diastereoselective reaction by introducing a chiral auxiliary in the rearrangement.Introducing diaryl bromium salt and diaryl chloronium salt into the domino process,with fine-tuning the conditions,the synthesis of the corresponding two types of biaryls was successfully realized.The kinetic resolution of 2-amino-2'-hydroxy-1,1'-binaphthyl derivative was achieved with chiral NHC as the catalyst by one-pot two-step method involving diaryl chloronium salt.Unreacted intermediate product was obtained in 32%total yield with 91% enantioselectivity.Domino arylation and regioselective rearrangement of N-arylhydroxylamine with diaryliodonium salts catalyzed by copper trifluoroacetate can also be realized.Faster synthesis of 2-amino-2'-hydroxy-1,1'-binaphthalene and its derivatives in 98% yield under mild conditions.1,1?-bi-2-naphthylamine(BINAM)and its derivatives were also achieved in moderate yield by using 2-naphthylhydrazine with appropriate protective group.Control experiments indicated that the key to this reaction is formation of aryl Cu(III)species during the reaction.Domino ligand exchange and regioselective rearrangement of 2-naphthol or1-naphthol with aryl iodide oxides catalyzed by Br(?)nsted acid were realized.Under mild conditions,2-hydroxy-2'-iodobinaphthalene and 4-hydroxy-4'-iodobiaryl were synthesized in about 60% yield by [3,3]-or [5,5]-rearrangement,respectively.Various chiral phosphoric acids were selected as the asymmetric catalysts for the transformation of 2-naphthol,the corresponding products was obtained in 55% yield with 41%enantioselectivity.2-Amino-2'-iodobinaphthyl could also be obtained with 31% ee via[3,3]-rearrangement reaction involving 2-naphthylamine and iodinonaphthalene.Through introducing two formate groups at the benzylic position of the substrate,the first rearrangement reaction of benzyl naphthyl ethers was successfully developed.The regioselective rearrangement of dimethyl 2-(2-naphthyl)-2-(2-naphthyloxy)malonate was realized with tin tetrachloride or titanium tetrachloride as the catalyst.Under mild conditions,dimethyl 2-hydroxy-2'-propanedioate binaphthyl was obtained in about 70% yield.In order to realize stereoselective control of the rearrangement chiral N-trifluoromethanesulfonyl phosphimides were selected as the catalysts in acetonitrile at 80 °C,however,only 10% enantioselectivity was obtained after screening different reaction condition parameters.In summary,three methods for the synthesis of biaryl compounds through the formation of stereogenic axis were developed.A series of structurally diversified biaryl compounds were obtained through highly selective C-H arylation reaction,domino assembly-rearrangement reaction or C-O linked diaryl rearrangement reaction.BINOL,NOBIN and BINAM are the core structures of various catalysts and ligands,and other biaryl products bearing iodine or hydroxyl substituents could be further transformed into functionalized reagents.