Synthesis Of Planar Chiral[2.2]Paracyclophane NHC Precursors And Their Application In The Asymmetric Addition Reaction

Chirality exists widely in lots of natural compounds which have some unique characteristics and functions.Enantiopure diarylmethanols,as a kind of very impotant chiral compounds,are key structural elements in a number of biologically and pharmaceutically active compounds and therefore represent important synthetic targets.The catalytic enantioselective synthesis of diarylmethanols has been the focus of many studies.An attractive route to chiral diarylmethanols is the catalytic asymmetric addition of aryl organometallic reagents to aldehydes.Among various organometallic reagents used,organoboron reagents are more desirable due to the advantages of their less toxic and air stable.On the other hand,N-heterocyclic carbenes(NHCs),as the alternative to phosphine ligands,have become a well-studied and well-utilized class of ligands in the field of transition metal-catalyzed reactions.In spite of these efforts,the research for efficient chiral ligands to generate high enantioselectivities in such reactions still remains an important challenge.In recent years,cyclophane compounds,due to their unique properties,attract more and more attention.Especially the[2.2]paracyclophane derivatives,which have two benzene ring plane nearly parallel to each other,have two ? bond overlap each other so as to form a larger ? system.Because of the sepecial structures,[2.2]paracyclophane compounds generally have some very unique properties.On the other hand,it is very easy to introduce chirality to[2.2]paracyclophane derivatives,and so they can be used as very good catalyst precursors in various asymmetric catalytic reactions.Our research group are working on the design and synthesis of N-heterocyclic carbene ligands and their metal complexes based on[2.2]paracyclophane,and finally use them in various asymmetric catalytic reactions.The main contents of this thesis are as follows:Chapter 1 BackgroundThis chapter first introduced the classification and the synthesis of various types of derivatives based on[2.2]paracyclophane.the resolution of planar chiral[2.2]paracyclophane-based compounds and as the catalyst precursors,their application in the asymmetric catalytic reactions through citing some representative examples.Then we made a systematic review of the N-heterocyclic carbenes,including the classification,the synthesis of various N-heterocyclic carbenes and their metal complexes.Finally we emphatically introduced the application of the N-heterocyclic carbene metal complexes in the asymmetric catalytic reactions.Through the summary of a large number of relevant literatures,we established our research direction.Chapter 2 Synthesis of novel NHC Ag and Rh complexes derived from[2.2]paracyclophane and their application in the asymmetric 1,2-addition of arylboronic acids to aromatic aldehydesBased on the literatures and our years' rich experience on the[2.2]paracyclophane,it was suggested that the alkoxy group on the ligand backbone could play an important role in the transition-metal-catalyzed asymmetric transformation.The modular structure of this type of ligands had attracted our attention.Very recently,our group has reported some alkoxy-substituted NHC precursors and their complexes derived from[2.2]paracyclophane.These ligands and complexes were also successfully applied in the asymmetric 1,2-addition of arylboronic acids to aromatic aldehydes.However,due to the flexibility related to the free rotation about the C-N bond connecting the imidazolium ring and[2.2]paracyclophane moieties,these ligands did not show satisfactory efficiency in the asymmetric arylation of aldehydes.In order to improve the enantioselectivities,we designed a new family of ligands to reduce the free rotation through linking the two alkoxy substituents on the paracyclophane.Herein,we report the synthesis of macrocyclic chiral[2.2]paracyclophane-based NHC precursors as well as their silver complexes and their application in the enantioselective addition of arylboronic acids to aromatic aldehydes.At last,through the screen of reaction conditions,we optimized the best silver complex.Using this optimal silver complex as the catalyst precursor of the enantioselective 1,2-addition of arylboronic acids to aromatic aldehydes,we got the chiral diarylmethanols with moderate enantioselectivities(up to 72%ee),much better than that we got before.Chapter 3 Synthesis of oxazoline-carbene Cu(I)complexes with planar and central chirality based on[2.2]paracyclophane and their application in asymmetric ?-boration of ?,?-unsaturated estersAt the beginning of this chapter,several oxazoline-carbene Cu(I)complexes with planar and central chirality based on[2.2]paracyclophane were synthesized.Then,these oxazoline-carbene Cu(I)complexes were used in the ?-boration of ethyl cinnamate with B2Pin2 to choose the most suitable catalyst for this asymmetric reaction.Next,other reaction conditions(solvent,base,temperature)were screened and the optimal reaction condition was selected.Then,various a,p-unsaturated esters were investigated to examine the applicability of this catalytic system.Fortunately,most of the desired products were obtained with enantioselectivity higher than 90%ee,even up to 97%ee.Excellent results showed the newly-designed oxazoline-carbene Cu(?)complexes based on[2.2]paracyclophane were very suitable for the ?-boration of ?,?-unsaturated esters.At last,the transition states of this catalytic reaction were postulated.Chapter 4 Synthesis of NHC Cu(?)complexes based on[2.2]paracyclo-phane and their application in the asymmetric borationIn this chapter,we synthesized a series of planar chiral imidazolium salts derived from the pseudo-ortho-substituted[2.2]paracyclophane skeleton and evaluated their transannular electronic effects and chiral discrimination ability based on the Cu-catalyzed asymmetric(?-boration of ?,?-unsaturated esters.Our efforts led to the development of the fluorine-substituted catalyst(Sp)-96-CuCl,which exhibited an exceptionally high reactivity and enantioselectivity(up to 97%ee)in the asymmetric boration reaction by virtue of transannular electronic effects.This is the first successful example of an electronic tuning of the chiral carbene center on the catalytic performance of relevant complexes,which might provide a new direction to the design of the chiral carbene backbone.The main innovation of this thesis was as follows:1.The macrocyclic crown ether-type ligands based on[2.2]paracyclophane were designed and synthesized for the first time.Besides,these lignds were also successfully used to the Rh-catalyzed asymmetric 1,2-addition of arylboronic acids to aromatic aldehydes(up to 72%ee).2.Several oxazoline-carbene Cu(?)complexes with planar and central chirality based on[2.2]paracyclophane were first synthesized and successfully applied to the asymmetric ?-boration of ?,?-unsaturated esters.Various chiral ?-hydroxyl esters were obtained with enantioselectivity higher than 90%ee,even up to 97%ee.3.Ligands derived from[2.2]paracyclophane with substituents having different electronic properties on the phenyl ring were designed and synthesized.Besides,these lignds were also successfully applied to the Cu(?)-catalyzed asymmetric?-boration of ?,?-unsaturated esters and a variety of chiral P-hydroxyl esters were obtained in excellent enantioselectivities(up to 97%ee)and yields(up to 99%).4.The catalytic performance and chiral discrimination ability of[2.2]paracyclophane-based NHC-copper complexes in the asymmetric boration controlled by the electronic tuning of carbene ligands were investigated for the first time.This is a successful example of an electronic tuning of the chiral carbene center on the catalytic performance of relevant complexes,which might provide a new direction to the design of the chiral carbine backbone.