Design and synthesis of chiral organopalladium-amine complexes

This thesis describes the design and synthesis of chiral organopalladium-amine complexes and their applications in stoichiometric asymmetric synthesis. A brief introduction on the organopalladium-amine complexes, the research development and the objective of this project were presented in Chapter 1. In Chapter 2, a functionalized amine, 1-(2,5-di-tert-butylphenyl)-N,N-dimethylethanamine was designed and synthesized, but the ortho¬-palladation reaction did not give the desired palladacycle. An unexpected C−N bond cleavage was observed and gave two C−N bond cleavage complexes. The mechanistic studies on the formation of C−N bond cleavage complex was carried out, but no substantial conclusion can be made yet. The initial step is likely β-hydride elimination and it is a base promoted reaction. Chapter 3 describes the synthesis of slightly less bulky amine ligand, 1-(2,5-di-iso-propylphenyl)-N,N-dimethylethanamine from p-di-iso-propylbenzene. By optimizing the reaction conditions including replacement of some of the reagents, it resulted in increased of the overall yield of the amine ligand. The ortho¬-palladation reaction gave the desired palladacycle and C−N bond cleavage complex by varying the palladating agent used. The racemic dimeric complex was resolved by separation of the (S)-prolinate diastereomeric derivatives via column chromatography. The efficiency of the palladacycle was assessed via the asymmetric intramolecular endo-cycloaddition reaction and a better stereoselectivity was obtained. In chapter 4 describes the synthesis of an electron-withdrawing group functionalized benzyl palladacycle to investigate the electronic effect of the palladacycle in asymmetric Diel-Alder reaction. The amine ligand, 1-(2,5-dichlorophenyl)-N,N-dimethylethanamine was synthesized via three step synthetic route with high overall yield and ortho¬-palladation with Pd(OAc)2 to give the acetate-bridged dimeric palladacycle. The racemic dimer was resolved with optically active sodium prolinate and by treatment of the corresponding diastereomer with aqueous 1M HCl produced the chiral chloro-bridged dimer. The efficiency of the palladacycle was examined via Diels-Alder reaction between DMPP-coordinated complex and ethyl vinyl ketone, however poor stereoselectivity was observed. The chiral dimeric complex was converted to the cationic complex and used in asymmetric hydrophosphination reaction between diphenylphosphine and DMAD to give one diastereomeric product.DOCTOR OF PHILOSOPHY (SPMS

Synthesis, optical resolution, and stereochemical properties of a rationally designed chiral C–N palladacycle

A novel racemic tertiary amine, 1-(2,5-diisopropylphenyl)-N,N-dimethylethanamine, was synthesized from 2,5-diisopropylbenzaldehyde via a multistep approach in high overall yield. The ortho palladation of this ligand was found to be sensitive to the reaction conditions and the palladating reagents employed. The metal complexation process could thus generate a cyclopalladated complex in high yield, lead to an unexpected N-demethylated amine palladium(II) complex, or both. Both products have been isolated and characterized crystallographically in the solid state and spectroscopically in solution. The racemic cyclopalladated complex could be efficiently resolved via the formation of (S)-prolinato derivatives. The absolute stereochemistries of the resolved diastereomeric complexes were determined by single-crystal X-ray crystallography in the solid state and by 1H–1H rotating frame Overhauser effect (ROESY) NMR spectroscopy in solution. An evaluation of the sterically hindered resolved cyclopalladated units as chiral auxiliaries was conducted in the endo-cycloaddition reaction between 3,4-dimethyl-1-phenylphosphole (DMPP) and ethyl vinyl ketone. The two expected phosphanorbornene adducts were generated with moderate stereoselectivity.Accepted versio

Synthesis, Optical Resolution, and Stereochemical Properties of a Rationally Designed Chiral C–N Palladacycle

A novel racemic tertiary amine, 1-(2,5-diisopropylphenyl)-<i>N</i>,<i>N</i>-dimethylethanamine, was synthesized from 2,5-diisopropylbenzaldehyde via a multistep approach in high overall yield. The ortho palladation of this ligand was found to be sensitive to the reaction conditions and the palladating reagents employed. The metal complexation process could thus generate a cyclopalladated complex in high yield, lead to an unexpected N-demethylated amine palladium­(II) complex, or both. Both products have been isolated and characterized crystallographically in the solid state and spectroscopically in solution. The racemic cyclopalladated complex could be efficiently resolved via the formation of (<i>S</i>)-prolinato derivatives. The absolute stereochemistries of the resolved diastereomeric complexes were determined by single-crystal X-ray crystallography in the solid state and by ¹H–¹H rotating frame Overhauser effect (ROESY) NMR spectroscopy in solution. An evaluation of the sterically hindered resolved cyclopalladated units as chiral auxiliaries was conducted in the endo-cycloaddition reaction between 3,4-dimethyl-1-phenylphosphole (DMPP) and ethyl vinyl ketone. The two expected phosphanorbornene adducts were generated with moderate stereoselectivity