| Chirality is the general character in nature, most of biomolecules exist in single enantiomer. Because of the enantiomers having the different biological activities, the asymmetric synthesis attracted great interest. Over the last decade, remarkable advances have been made in the asymmetric organometallic catalysis. The enantioselective catalysis has become one of the most important frontiers in exploratory organic synthetic research. A key factor in successful enantioselective catalysis is the structure of chiral ligands. Recently, as a chiral source, planar chiral [2.2]paracyclophane derivatives have been successfully applied in asymmetric catalysis. Planar chiral [2.2]paracyclophane-based ligands are so stable that they racemize only at high temperature, and such a versatile backbone structure opens the possibility of designing different types of chiral ligands. In the investigation of efficient chemical transformation, the C-C bond-forming plays an outstanding role. In this context, the asymmetric organometallic catalysis has achieved considerable attention. Among them, the asymmetric addition of organoboronic acids to aldehydes is a challenge work. The product of these reactions is chiral diarylmethanols, which are important intermediates for the synthesis of biologically and pharmaceutically active compounds. Since Miyaura first reported the Rh-catalyzed asymmetric1,2-addition of organoboronic acids to aldehydes in1998, Due to the stability, low toxicity and easy manipulation of organoboronic acids, the asymmetric addition of organoboronic acids to aldehydes attracted great interest. Recently, various transition metals have been successfully applied in the reaction, such as rhodium, ruthenium, palladium, nickel and copper. Notably, significant attention has been paid to apply rhodium catalysts in the formation of C-C bonds, because of their special catalytic activity and selectivity compared to other metal catalysts. As a promising alternative ligand to the currently used phosphines, the NHC ligands showed great application potentiality in the asymmetric arylation reaction.In conclusion, we focus on the [2.2]paracyclophane chemistry and NHC catalytic C-C formation reactions. A series of halo/alkoxy/sulfonate-substituted planar chiral carbene precursors and novel planar chiral N-heterocyclic carbene complexes based on the [2.2]paracyclophane skeleton have been prepared and applied in asymmetric additions of organoboronic acids to aldehydes and asymmetric β-boration of α,β-unsaturated carboxylic esters/ketones. All the transformations show better selectivity and higher catalytic activity by optimizing the reaction conditions.The main contents of the thesis are shown as follows:Chapter1The review of the [2.2]paracyclophane derivatives, N-heterocyclic carbenes precursors, NHC-metal complexes and their application in asymmetric catalysis introduce our research background, which supported our research in theory.Examples of [2.2]paracyclophane-based ligands include carboxylic acid derivatives, imines, oxazoline-phosphanes, oxazoline-benzyl alcohols, imidazoliums, dihydroimidazoliums, diphosphanes and so on. They have been applied successfully in various reactions, such as asymmetric hydrosilylation, asymmetric hydrogenation and asymmetric organozinc addition reactions etc. In the other hand, a great deal of methods to synthesize NHC precursors provided adequate support for our research. They also have achieved great success in a series of reactions such as olefin metathesis, hydrosilylation, and cross-coupling reactions etc. The preparation of NHC-precursors based on [2.2]paracyclophane has allowed an almost infinite access to the asymmetric catalysis.Chapter2Design and synthesis of new alkoxy/sulfonate-substituted carbene precursors derived from [2.2]paracyclophane. They were applied in the Rh-catalyzed asymmetric addition of arylboronic acids to aromatic aldehydes, affording chiral products with high yields and moderate enantioselectivities.We designed and synthesized various new planar chiral imidazoliums and imidazoliniums derived from [2.2]paracyclophane. The synthesis began with the [2.2]paracyclophane. By several synthesis procedures and resolve methods, we got enantiomerically pure4-amino-12-bromo[2.2]paracyclophane and4-amino-13-bromo[2.2]paracyclophane. Then, by diazotization, hydrolization, alkylation and sulfonation, we obtained several4,12-disubstituted [2.2]paracyclophanyl amines and4,13-disubstituted [2.2]paracyclophanyl amine. These amines reacted with aqueous glyoxal to furnish the corresponding diimines. The diimines were treated with the solution of silver triflate and chloromethyl pivalate to form imidazolium triflates. The imidazolium bromide was obtainded from its triflate analogue by anion exchange with saturated KBr aqueous solution. In addition, the imidazolinium tetrafluoroborate was synthesized by converting dimine into the corresponding diamine with B2H6, and ring-closing with triethyl orthoformate. With these novel imidazoliums and imidazoliniums in hand, we then turned our attention to their application in asymmetric arylation of aldehydes. Finally, by testing solvents, rhodium sources, ligands and substrates, these planar chiral carbene precursors showed better enantioselectivity than our reported ligands (up to99%yields, up to54%ee).Chapter3Design and synthesis of novel planar chiral Ag and Rh N-heterocyclic carbene complexes derived from [2.2]paracyclophane, their structure were characterized, even single-crystal X-ray diffraction data further confirmed the molecular structure. They were applied in ultrasound assisted asymmetric addition reactions of organoboronic acids to aromatic aldehydes, higher catalytic activities were obtained (up to94%yields, up to67%ee).We designed and synthesized several new planar chiral NHC-Ag and NHC-Rh complexes based on [2.2]paracyclophane. Our synthetic route to the new NHC-metal complexes were started from enantiomerically pure [2.2]paracyclophanyl imidazolium triflate. By anion exchange of the imidazolium triflates, then reacted with Ag2O in CH2Cl2, we obtained NHC-Ag complex. NHC-Ag2undergo a facile reaction with rhodium sources to form NHC-Rh complex. The X-ray diffraction data further confirmed the molecular Rh[(COD)NHC]Cl. With the planar chiral NHC-metal complexes, we preliminarily examined their application in the asymmetric additions of organoboronic acids to aldehydes. Finally, under ultrasound irradiation, the planar chiral NHC-Rh complexes can achieve higher catalytic activities in the asymmetric addition of arylboronic acids to aromatic aldehydes, and the best results are observed with the combination of NHC-Ag5and RhCl3(up to94%yields, up to67%ee). However, the reaction condition above were not suitable for the heterocyclic substrates, only low enantioselectivities could be obtained.Chapter4Design and synthesis of new halogen/methoxyl-substituted NHC-Cu complexes derived from [2.2]paracyclophane, the ligand structures were characterized. They were applied in the asymmetric β-boration of α,β-unsaturated ketones and carboxylic esters, the better catalytic results were obtained.We designed and synthesized several new planar chiral halogen/methoxyl-substituted NHC-Cu complexes based on[2.2]paracyclophane. By diazotization, amination, hydrolization and so on, we obtained several fluoro-substituted [2.2]paracyclophanyl amines. These amines reacted with aqueous glyoxal to furnish the corresponding diimines. The diimines were treated with the solution of silver triflate and chloromethyl pivalate to form imidazolium triflates. The imidazolium bromide was obtainded from its triflate analogue by anion exchange with KBr. The imidazolium bromides undergo a facile reaction with Cu2O to form NHC-Cu complexes. With these NHC-Cu complexes, we then turned our attention to their application in the asymmetric β-boration of a, β-unsaturated ketones and carboxylic esters. Finally, by testing solvents, rhodium sources, ligands and substrates, the planar chiral NHC-Cu complexes can achieve higher catalytic activities in the asymmetric β-boration of α, β-unsaturated ketones and carboxylic esters (up to94%yields, up to94%ee).The main innovation of this thesis was shown as follows:1. A serious of new planar chiral imidazoliums and imidazoliniums based on [2.2]paracyclophane skeleton were designed and synthesized. New alkoxy/sulfonate-substituted NHC precursors, halo-substituted NHC precursors, planar chiral [2.2]paracyclophane dihydroimidazoliums/imidazoliums were synthesized. Their structures were characterized by1H and13C NMR, high-resolution mass spectrometry (HRMS), elemental analysis and Single-crystal X-ray diffraction.2. Several novel planar chiral N-heterocyclic carbene metal complexes based on [2.2]paracyclophane have been prepared. These complexes were fully characterized by1H and13C NMR, high-resolution mass spectrometry (HRMS) and elemental analysis. Single-crystal X-ray diffraction data further confirmed the molecular structure of NHC-Rh complex3.3. We examined the NHC precursors and NHC-metal complexes in the asymmetric addition of organoboronic acids to aldehydes. By optimized the reaction conditions, these planar chiral NHC precursors can achieve higher catalytic activities for the in stu Rh-catalyzed asymmetric arylation of aldehydes. In order to improve the enantioselective, NHC-Rh complexes were used in the asymmetric addition of organoboronic acids to aldehydes and the best results are observed in67%ee.4. We have also examined these NHC precursors in the Cu(Ⅰ)-catalyzed asymmetric β-boration of α, β-unsaturated ketones and carboxylic esters. The procedure tolerates a relatively wide range of substrates and shows high reactivity (up to94%yield) and excellent selectivity (up to94%ee). |
PDF Full Text Request