Design, synthesis and applications of chiral functionalized phosphapalladacycles

• Main Author: Li, Xirui
• Other Authors: Leung Pak Hing
• Format: Theses and Dissertations
• Language: English
• Published: 2019
• Subjects: DRNTU::Science::Chemistry
• Online Access: https://hdl.handle.net/10356/81278; http://hdl.handle.net/10220/47497
• Institution: Nanyang Technological University

This thesis is focused on the design, synthesis and application of a series of Cstereogenic functionalized naphthyl CP phosphapalladacycles with five-membered organometallic ring within its framework via a stepwise asymmetric hydrophosphination and metalation procedure. According to the effective catalytic properties and tedious synthesis procedures of the chiral CP palladacycle derived from 1-(1-naphthyl)ethyldiphenylphosphine, it is urgent to design new catalysts. We designed and synthesized its analogues with catalytic methods through atom economic green way and saving the chiral auxiliaries to proceed the resolution. The optically active phosphine ligands for the palladacycles were synthesized via the asymmetric catalytic P-H addition of diphenylphosphine across activated double bonds. The optimization of the conditions was conducted by screening the solvents, temperature, base, catalysts and functional group. The enantiomeric excess values of the chiral phosphine ligands were determined by 31P{1H} NMR spectroscopy upon coordination of the ligands to chiral CN palladium complexes forming a pair of diastereomers or by HPLC after sulfuration of the free air-sensitive ligands. The conversion of the phosphine ligands was determined by 31P{1H} NMR spectroscopy. Normally polar solvents tend to accelerate the reaction rates and shorten the reaction time. A lower temperature induced better enantiomeric excess albeit with long time. The base was necessary to activate the P-H bond. The mechanism of the P-H addition was also explained in this thesis in Chapter 5. The conditions of metalation were optimized by screening the base, solvent, palladium source, and purify procedures. In Chapter 1, an introduction to the synthesis and application of CN and CP cyclopalladated five-membered complexes with/without the chiral center is presented. In the end, the works of our lab in the past decade were classified and discussed. The CN complexes and their CP and CAs analogues have similar synthetic pathway andVI properties as they belong to the same main group in the periodic table, and all of them have a lone pair electron that can coordinate to the metal such as Pd, Ir, Pt, Fe etc. However, they are different with each other as the phosphorus and arsenic have the vacant orbitals, which can back-donating from the metal. In Chapter 2, the intricate reason of how various functional groups borne on the substrate can influence the performance of selected palladacycle catalysts is explored in this study, providing valuable insights on the choice of catalyst for structurally distinct substrates. The employment of a mono-coordination site palladium pincer catalyst circumvents catalyst inactivation by the starting material, facilitating the first known asymmetric preparation of phosphines bearing a diketone functionality. While the ee values obtained are at best moderate, modifications to the pincer catalyst could potentially engender improvements in the obtained results. A plausible mechanistic cycle has been proposed for the asymmetric hydrophosphination reaction. In Chapter 3, a chiral phosphine auxiliary was generated quantitatively with excellent ee via catalytic asymmetric hydrophosphination of 3-(naphthalen-1- ylmethylene)pentane-2,4-dione. The subsequent metal complexation of the monophosphine yielded two different coordination complexes depending on the reaction conditions. The ortho-palladation of both coordination complexes resulted in the formation of a single dimeric phosphapalladacycle complex that could be further converted to the monomeric bisacetonitrile derivative. Moreover, the palladium complex exhibits interesting oxophilicity as the stable bisaquo derivative could be isolated and characterized crystallographically. The catalytic potential of the phosphapalladacycle was also demonstrated. The main factor preventing the advancement of bidentate phosphapalladacycles in asymmetric catalysis has been overcome successfully. The simple catalytic protocol (Scheme 38, Table 6) is attractive due to the efficiency in preparing chiral phosphine auxiliaries quantitatively without the need for classical resolution techniques. A preliminary investigation on the catalytic potential of the new palladacycle was promising, yielding the desired product with excellent ee. It was keptVII a positive outlook towards the prospects of the new phosphapalladacycle catalyst. In light of previous experience, the benefits of installing an ester functional group as opposed to a simple methyl group in the palladacycle backbone should be highlighted. It was reported that a P-H bond addition reaction did not proceed in the presence of a pincer catalyst with methyl substituents, but the same reaction could be conducted with an analogous pincer catalyst with ester functionalities. Further developments in the architecture of the palladacycle complexes will be conducted and their application in other transformation reactions will be examined. In Chapter 4, four functionalized chiral phosphapalladacycle complexes have been efficiently prepared by sequential asymmetric hydrophosphination (P-H reaction) and cyclometallation reaction. The impact of installation of malonate moiety at the chiral carbon as well as the modification of the naphthalene ring system was studied for the asymmetric hydrophosphination reaction. These preliminary results will serve as a guide for the rational design of other functionalized phosphapalladacycles using this alternate synthetic methodology. In Chapter 5, an optically active fluorosulfonyl-phosphine ligand has been prepared via cyclopalladated complex catalyzed asymmetric P-H addition reaction in technically quantitative yield with up to 90% ee under mild conditions. Several readily available CP-palladacycles could be employed as catalysts with similar efficiency for the asymmetric addition reaction. Currently, the synthetic applications and biological properties of the novel chiral sulfonyl-substituted phosphine and its metal complexes are studied in our group