Synthesis Of Planar Chiral N-Heterocyclic Carbene Precursors Derived From [2.2] Paracyclophane And Their Application In Asymmetric Catalysis

The element of planar chirality plays an increasingly important role in modern organometallic chemistry. The field of [2.2]paracyclophane chemistry has developed considerably since these compounds first attracted the interest of chemists in the middle of the last century. Recently, there has been notable progress, especially regarding the synthesis of new derivatives and their applications in asymmetric catalysis. The asymmetric arylation of aldehydes has recently received considerable attention because chiral diarylmethanols are key structural elements in an array of pharmacologically active compounds and are, for that reason, important synthetic targets. Complexes with N-heterocyclic carbenes (NHCs) have, during the years, gathered considerable interest from the organic chemistry community and have been widely used in homogeneous metal catalysis. The Rh-NHC-catalyzed addition of arylboronic acid derivatives to aldehydes deserves particular mention because these methods present high efficiency with a reasonable tolerance towards polar substituents in the substrates.The above findings and our interests in [2.2]paracyclophane chemistry and C-C formation reactions triggered our efforts to develop new planar chiral imidazolium salts as NHC precursors based on [2.2]paracyclophane for application in homogeneous catalysis. We herein report the synthesis of a new family of planar chiral imidazolium salts based on [2.2]paracyclophane and their application in the asymmetric rhodium-catalyzed 1,2-addition of arylboronic acids to aldehydes.The main content of the thesis was shown as follows:1. Review of the synthesis and application of the chiral ligands based on [2.2]paracyclophane.Planar chiral [2.2]paracyclophane-based ligand possesses a rigid [2.2]paracyclophanyl unit, and such a versatile backbone structure opens the possibility of designing different types of chiral ligands. The thus far reported [2.2]paracyclophane-based ligands include oxazoline-phosphanes, imidazoliums, oxazoline-alcohols, imine, diphosphanes ligands and so on. In addition, the ligands based on [2.2]paracyclophane have demonstrated catalytic activity for a series of reactions such as hydrosilylation, hydrogenation, allylic substitution, arylamination and organozinc addition reactions etc.2. A new family of planar chiral imidazolium salts based on [2.2]paracyclophane was synthesized.In our synthetic pathway to the planar chiral imidazolium salts, the compounds Sp-4-amino-12-bromo[2.2]paracyclophane 1a and (4Rp,13Sp)-amino-13-bromo[2.2] paracyclophane 2a are the key structural elements. Following the literature methods, we got the two intermediates and we improved the reaction conditions in many ways. One of the important characteristics of 1a and 2a is the fact that they are easily tunable in their steric profile. Suzuki-Miyaura coupling with arylboronic acids under Pd-dppf catalysis gave the sterically hindered amino[2.2]paracyclophanes in good to excellent yields (85-99%). Treatment of the substituted amino[2.2] paracyclophanes with aqueous glyoxal in THF at room temperature gave corresponding diimines in essentially quantitative yield. We were pleased to find that a reagent formed from equal amounts of silver triflate and chloromethyl pivalate resulted in the formation of the desired imidazolium triflates in moderate to good yields (54-91%).3. The application of the synthesized planar chiral 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 with one ligand, 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. Even with 0.03 mol % of the catalyst, the reactions were carried out rapidly and gave the chiral diarylmethanols in excellent yields. The optimized protocol was tested in the asymmetric arylation of aldchydes 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 52%) with only 0.3 mol% catalyst. 4. Silver N-Heterocyclic Carbene Complexes were synthesized successfully and their application in the synthesis of carbene-Rh complexes was studied.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. Three novel planar chiral crown ether-based imidazolium salts were synthesized. And then we transferred the synthesized imidazolium triflates into the corresponding imidazolium chloride. Treatment of the imidazolium chloride with silver oxide gave the desired silver NHC complexes. The silver NHC complexes reacted with rhodium precatalyst to form the desired product rhodium-NHC complexes. Then the synthesized Rh-NHC complexes were applied in the catalytic addition of arylboronic acids to aromatic aldehydes. For some ligand, the complexes revealed almost the same activity with the optimized protocol in the part three and a slight superior enantioselectivity.5. Chrial thiourea derivatives based on the [2.2]paracyclophane were synthesized and their application in homogeneous catalysis was reported.Over the last decade the potential for N,N-dialkyl thiourea derivatives to serve as active metal free organocatalysts for a wide range of synthetically useful reactions susceptible to the influence of general acid catalysis has begun to be realised. In this part, we synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral [2.2]paracyclophanes scaffold. Among them, thiourea bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be efficient for the asymmetric Michael reaction of 1,3-dicarbonyl compounds to nitroolefins.6. Chiral diamine ligands based on the [2.2]paracyclophane were synthesized and their application in enantioselective transfer hydrogenation was studied.Asymmetric transfer hydrogenation of ketone is an intriguing and useful synthetic methodology to yield chiral alcohols. Chiral diamine ligands have been utilized as catalysts for this purpose and exhibit excellent activity and enantioselectivity. In this thesis, a series of new chiral ligands based on the [2.2]paracyclophanes was synthesized and show certain activity in the asymmetric transfer hydrogenation of ketone.The main innovation of this thesis is the synthesis of the planar chiral imidazolium triflates and their applicability in rhodium-catalyzed asymmetric additions of arylboronic acids to aromatic aldehydes. Another innovation of this thesis is the synthesis of the silver NHC complexes and Rh- NHC complexes from silver NHC complexes. The Rh- NHC complexes were successfully applied in the catalytic addition of arylboronic acids to aromatic aldehydes.