Synthesis Of Planar Chiral Alkoxy [2.2]Paracyclophane Imidazolium Salts And Their Application In Asymmetric Catalysis

Since the last century, the homogeneous asymmetric catalysis plays an increasingly important role in modern organic chemistry. [2.2]Paracyclophane needs only one substituent to generate planar chirality, and its derivatives are so stable that they racemize only at high temperature. Because of these properties, [2.2]Paracyclophane is regarded as very good backbone for chiral ligand which applied in asymmetric catalysis. Recently, much attention has been paid to the asymmeric 1,2-addition of arylboronic acid to aldehydes beacause the chiral diarylmethanols are key intermediates for the synthesis of pharmaceutically and biologically active compounds, since Miyaura first reported in 1998. On the other hand, N-heterocyclic carbenes (NHCs) have been succesfully employed in various homogeneous metal-catalyzed reactions. Among these, NHC-metal complexes showed good potential in asymmetric addition of arylboronic acid derivatives to aldehydes derivatives, as they are neutral,?-donating ligands with negligible?backbonding. However, there are scarce succesful examples that employed N-heterocyclic carbene ligands in this type of reaction. More efficient chiral catalysts were desired to improve the enantioselectivities.According to the above mentioned, we synthesized a new family of planar chiral alkoxy [2.2] paracyclophane imidazolium salts, and employed them in the asymmeric1,2-addition of arylboronic acid to aldehydes as carbene precursors.The main content of the thesis was shown as follows:1. Review of the [2.2]paracyclophane derivatives and N-heterocyclic carbenes compands.Planar chiral [2.2]paracyclophane ligand possesses a rigid [2.2]paracyclophanyl unit, and the versatile backbone structure offers the possibility of designing different types of chiral ligands. The known [2.2]paracyclophane-based ligands include imidazoliums, oxazoline-phosphanes, oxazoline-alcohols, imine, diphosphanes ligands and so on. In addition, the [2.2]paracyclophane ligands based have demonstrated catalytic activity for a number of reactions such as hydrosilylation, allylic substitution, hydrogenation, arylamination and organozinc addition reactions etc.2. Developed an efficient catalyst system for Pd-Catalyzed amination of[2.2]paracyclophanyl bromidesA practical Buchwald-Hartwig amination of [2.2]paracyclophanyl bromides with benzhydrylideneamine is developed. The method provides a facile route to a variety of imino and amino [2.2]paracyclophanes that are otherwise not readily synthesized.3. A new family of planar chiral alkoxy imidazolium salts based on[2.2]paracyclophane was synthesized.Several planar chiral alkoxy imidazolium salts have been prepared. Starting from optical pure 4-amino-12-bromo[2.2]paracyclophane and 4-amino-13-bromo[2.2] paracyclophane, treatment of this substrate with excess NaNO2 in 2:1 acetic anhydride/acetic acid at 0?, followed by warming to room temperature,was carried out to synthesize acetoxy [2.2]paracyclophane.During hydrolysis and alkylation of the acetoxy compound,we got alkoxy [2.2]paracyclophane. Amination of alkoxy[2.2]paracyclophane bromides with benzhydrylideneamine, used Pd-DPPF as catalyst, NaOBu-t as the base, and toluene as the solvent, was performed to give benzhydrylideneamino[2.2]paracyclophane derivatives. After cleavage of the imine with HCl, we treated amino[2.2]paracyclophane derivatives with aqueous glyoxal in THF to obtain corresponding diimines.The diimine was treated with the solution of AgOTf and chloromethyl pivalate in dark at 40?to form the imidazolium trifluoromethanesulfonates. In addition, the methoxyl imidazolinium tetrafluoroborate was synthesized from [2.2]paracyclophane diimine, by hydrogenation with NaBH4/20% H2SO4 and then ring-closure with triethyl orthoformate in the presence of a catalytic amount of formic acid. All the imidazolium and imidazolinium salts were purified, and fully characterized by NMR, mass spectrometry.4 The application of the synthesized planar chiral alkoxy imidazolium salts as NHC precursors in the rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes.Imidazolium salts thus obtained were then used as precursors for rhodium-NHC complexes, which were applied in the catalytic addition of arylboronic acids to aromatic aldehydes. We began by optimizing the reaction conditions, a number of parameters were varied using phenylboronic acid and 1-naphthaldehyde as model substrates. These ligands reveal high activity in the rhodium-catalyzed asymmetric additions of arylboronic acids to aromatic aldehydes. The optimized protocol was tested in the asymmetric arylation of aldehydes with different steric and electronic properties. In most cases, the reaction can proceed with notable efficiency (up to 99% isolated yield) and moderate enantioselectivity (up to 54%).5. Synthesis of silver N-Heterocyclic Carbene Complexes and their application in the rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes.Silver NHC complexes have proven themselves to be very adept at transferring to a variety of other metals. Transmetalation reactions can be carried out under aerobic conditions and in the presence of water.In addition, three novel planar chiral crown ether-based imidazolium salts were synthesized. And then Treatment of the imidazolium salts with silver oxide gave the desired silver NHC complexes. The silver NHC complexes reacted with rhodium sources to form the desired product rhodium-NHC complexes. Then the synthesized Rh- NHC complexes were applied in the asymmertic addition of arylboronic acids to aromatic aldehydes. For methoxy ligand, the complexes revealed almost the same selectivities with the optimized protocol in the part three.The main innovation of this thesis is the development of efficient catalyst system for Pd-Catalyzed amination of [2.2]paracyclophanyl bromides. Another innovation of this thesis includes:the synthesis of the planar chiral alkoxy imidazolium triflates and their applicability in rhodium-catalyzed asymmetric additions of arylboronic acids to aromatic aldehydes, synthesis of the silver NHC complexes and Rh-NHC complexes from silver NHC complexes. The Rh-NHC complexes were successfully applied in the asymmeric addition of arylboronic acids to aromatic aldehydes.