Synthesis Of [2.2] Paracyclophane-based Oxazoline-carbene Ligands For Catalytic Asymmetric Silylation

Chapter 1,in this chapter,a brief introduction of the nomenclature of[2,2]paracyclophane derivatives,substitution patterns and the resolution of some typical compounds is given.Followed by a review of the application of[2,2]paracyclophane derivatives in catalytic asymmetric reactions during the past twenty years.[2,2]paracyclophane derivatives were widely used as ligands in the addition of organozinc to aldehydes;And the application of planar chiral phosphorus ligands based on[2,2]paracyclophane in transition metal catalyzed asymmetric hydrogenation reactions,C-C,C-X coupling reactions were also summarized as well as the application of planar chiral carbene ligands in asymmetric catalytic reactions.Chapter 2,synthesis of the imidazolium chlorides1,synthesis of 4-bromo-12-carboxyl[2.2]paracyclophaneAccording to the synthetic strategy reported previously by our research group,[2.2]paracyclophane was used as the starting material.After bromination,group translocation and carboxylation,4-bromo-12-carboxyl[2.2]paracyclophane was obtained.2,synthesis of 4-bromo-12-(4-isopropyloxazolin-2-yl)[2.2]paracyclophaneReaction of 4-bromo-12-carboxyl[2.2]paracyclophane with thionyl chloride resulted the corresponding acyl chloride,then the residue was reacted with(L)-valinol to affored the amide.4-bromo-12-(4-isopropyloxazolin-2-yl)[2.2]paracyclophane was obtained through cyclization of the amide,in the presence of PPh3/CCI4/NEt3 and acetonitrile as the solvent.3,synthesis of(S,Sp)-4-benzhydrylideneamino-12-(4-isopropyloxazolin-2-yl)[2,2]-paracyclophane.Reaction of 4-bromo-12-(4-isopropyloxazolin-2-yl)[2.2]paracyclophane with benzhydrylideneamine under Pd-catalyzed amination,afforded the corresponding imines(Rp,S)and(Sp,S)-4-benzhydrylideneamino-12-(4-isopropyloxazolin-2-yl)[2,2]-paracyclophane as the diastereoisomeric mixtures.The desired enantiopure(S,Sp)-4-benzhydrylideneamino-12-(4-isopropyloxazolin-2-yl)[2,2]paracyclophane was easily separated from the mixture of diastereoisomers by double recrystallization with ethanol rather than repeated column chromatography on silica gel.4,synthesis of new bidentate oxazoline-carbene precursors(S,Sp)-4-amino-12-oxazolinyl[2.2]paracyclophane was obtained through acid hydrolysis of(S,Sp)-4-benzhydrylideneamino-12-(4-isopropyloxazolin-2-yl)[2,2]par-acyclophane.Treatment of(S,Sp)-4-amino-12-oxazolinyl[2.2]paracyclophane with the corresponding pyridine aldehyde or quinoline aldehyde,afforded the imines which were not stable enough for further purification and used directly.Then the imines were reacted with a reagent formed from silver trifluoromethanesulfonate and chloromethyl pivalate,resulted in the formation of the imidazolium triflates.Finally,the desired imidazolium chlorides were obtained by anion exchange of their analogue triflates with an ion-exchange resin.5,synthesis of new monodentate carbene precursorReaction of(Sp)-4-amino[2,2]paracyclophane with 6-methylpyridine-2-carbaldehy-de afforded the corresponding imine,then(Sp)-3-{[2.2]paracyclophan-4-yl}-9-methyl imidazo[1,5-a]pyridinium chloride was prepared by the same procedure as for the bid-entate oxazoline-carbene precursors.Chapter 3,application of the above imidazolium chlorides in copper catalyzed entioselective 1,2-silylation of N-sulfonyliminesBy comparing the effects of different ligands,solvents,reaction temperature and bases on the yield and enantioselectivity,the optimal reaction conditions were achieved.Finally,the substrate scope was investigated with a variety of N-tosylaldimines.The corresponding chiral a-amino silanes could be obtained in excellent yields(90-98%)with high entioselectivities(86-97%).The main innovation of this paper:1.A series of new planar chiral bidentate oxazoline-carbene ligands based on[2,2]paracycophane were synthesized.Compared with the ligands previously reported by our group,the oxazoline unit was derived from L-valinol,which is much cheaper than L-tert-leucino.In addition,in order to achieve better catalytic performance,more reasonable structures have been designed and synthesized.2.Using the optically pure(SP)-4-amino[2,2]paracyclophane as the starting material,a new monodentate carbene precursor was synthesized,in which the oxazoline ring was not involved.3.This type of ligands was used in the copper catalyzed asymmetric 1,2-silylation reaction of the N-tosylaldimines for the first time,and a series of a-amino silanes was obtained in excellent yields with high ee values.