Synthesis Of Tetrahydroquinoxalines By Copper Catalyzed Cross-coupling

N-aryl compounds, especially chiral N-aryl compounds, play very importantroles in many life activities and have been applied to extensively broad use. Therefore,the development of synthetic method of the N-aryl compounds is investigated exten-sively today. With a century’s development, the Ullmann-typed C-N cross-couplingcatalyzed by copper has become one of the hottest research topics. Compare to theBuchwald-Hartwig reaction catalyzed by palladium, the Ullmann-typed C-Ncross-coupling catalyzed by copper has its unique advantages, namely:(1) the cost ofcopper catalyst is cheap,(2) without any need to use the toxic phosphorus-containingligands,(3) the reaction scopes are almost without limitations. All above are supposedto guarantee that Ullmann reaction have over-advantages in large-scale synthesis andapplications. Though Ullmann C-N cross-coupling catalyzed by copper has beenstudied extensively, CuI catalyzed cross-coupling of ortho-dihalogenated arenes withchiral di-amines to gain tetrahydroquinoxalines has not yet been reported.In the dissertation, we adopted CuI as catalyst, L-proline as ligand to catalyze theC-N coupling of chiral diamines with ortho-dihalogenated arenes to produce tetrahy-droquinoxalines.In order to get the best conditioned response, we probed the conditions into thekinds of copper source and ligands, the amount of catalysts, the different bases, theduration and the temperature. First of all, we attempted the reaction of1,2-diaminocyclohexane and ortho-bromo iodobenzene to screen out the optimal con-ditions: the duration was24h, the temperature was110℃, with a dosage ratio of1,2-diaminocyclohexane/o-bromo iodobenzene/CuI(as catalyst)/L-proline(as lig-and)/Cs2CO3(as base)=1.5:1.0:0.10:0.10:2.5(mmol).With the obtained optimal reaction conditions, we tried to expand the scopes of the reaction by applying other chiral diamines (prepared from DL-glycine, L-alanine,L-tyrosine, L-phenylglycine, L-tryptophan, L-valine, L-phenylalanine, L-tert-brightacid, L-isoleucine, L-proline) with o-bromo iodobenzene to go through theUllmann-typed C-N cross coupling reaction and by performing CuI C-Ncross-coupling reaction of diaminocyclohexane with ortho-dihalogenated areneswith different functional groups in the aromatic ring.We also attempted to synthesize two chiral ligands. We protected the hydroxylgroups of (R)-(+)-BINOL by substituting the hydrogen atoms of the hydroxyl groupswith chloromethyl methyl ether to give di-substituted product—BINOL-2MOM. Andthen4-phenyl phenylboronic acid was prepared from4-brominated phenyl benzene,which was taken to undergo a cross-coupling reaction with6,6’-dibro-mo-BINOL-2MOM under palladium-catalyzed conditions, removing MOM to yieldligands1.And by coupling6,6’-dibromo-BINOL-2MOM with carbazole under the cataly-sis of palladium and a following free of MOM to yield ligand2.