A novel amine ligand, 1-(2,5-dichlorophenyl)-N,N-dimethylethanamine, was synthesized from 1-(2,5-dichlorophenyl)ethanone via a three step synthetic route. Direct ortho-palladation of the amine ligand with Pd(OAc)(2) gave the racemic dimeric complex in high yield. This racemic palladacycle was efficiently resolved through the formation of its (S)-prolinato derivatives. The resulting diastereomeric complexes were separated efficiently by column chromatography. In the solid state, the structure and absolute configuration of the two optically resolved palladium complexes were determined by single crystal X-ray crystallography. In solution, their absolute conformations were also investigated by the 2D (1)H-(1)H rotating frame nuclear Overhauser enhancement (ROESY) NMR spectroscopy. Both (R,R) and (S,S)-di-μ-chloro dimeric palladium complexes could be obtained chemoselectively by treating the corresponding prolinato derivatives with dilute hydrochloric acid. The amine auxiliary could be subsequently removed from the palladium center by treatment with concentrated hydrochloric acid. The enantiomerically pure palladacycle was used to promote the asymmetric hydrophosphination reaction between diphenylphosphine and dimethyl acetylenedicarboxylate. The (31)P{(1)H} NMR spectroscopy indicated that only one stereo-isomeric product was formed.
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 1 H− 1 H 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.
Two structurally isomeric substituted N,N-dimethylethanamines have been prepared. Treatment of the 2,4-di-tert-butylphenyl isomer with Pd II ions generated the ortho-metalated complexes. On the other hand, treatment of the 2,5-di-tertbutylphenyl-substituted amine resulted in the unexpected chemoselective cleavage of one of the three N-C bonds, thus generating the corresponding secondary amine. The N-demethylation process could be catalyzed at room temperature by palladium(II) catalysts such as PdCl 2 or Pd(OAc) 2 .
Bn benzyl Bu butyl br broad c concentration for optical rotation analysis calcd calculated conc. concentrated CDCl3 chloroform-d1 CD2Cl2 dichloromethane-d2 CHCl3 chloroform CH3CN acetonitrile Claisen's alkali a strong base prepared by 8.81 g KOH dissolved in 6 ml of XI Summary 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,Ndimethylethanamine 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-diiso-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 endocycloaddition 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-(2,5dichlorophenyl)-N,N-dimethylethanamine was synthesized via three step synthetic XII route with high overall yield and ortho-palladation with Pd(OAc)2 to give the acetatebridged 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.