The discovery of efficient methods for gaining access to enantiomerically pure compounds has been a substantial challenge for chemists. Among the various ways to produce enantiopure compounds, asymmetric organic synthesis using either a stoichiometric or a substoichiometric amount of chiral auxiliaries/ligands has revealed a variety of versatile stereoselective reactions that complement biological processes. This thesis research focuses on design and synthesis of chiral arsines and applications in asymmetric Wittig reactions and the Pd-catalyzed asymmetric allylic alkylation and asymmetric Heck reaction....[ Read more ]

The discovery of efficient methods for gaining access to enantiomerically pure compounds has been a substantial challenge for chemists. Among the various ways to produce enantiopure compounds, asymmetric organic synthesis using either a stoichiometric or a substoichiometric amount of chiral auxiliaries/ligands has revealed a variety of versatile stereoselective reactions that complement biological processes. This thesis research focuses on design and synthesis of chiral arsines and applications in asymmetric Wittig reactions and the Pd-catalyzed asymmetric allylic alkylation and asymmetric Heck reaction.

Organic arsenic compounds, being the phosphorus analogs, play an important role in organic synthesis. A brief survey of current literature on preparation and applications of arsenic(III) and arsenic(IV) compounds is given in Chapter 1. Although arsines are known to be the ligands superior to phosphines in a number of transition metal-catalyzed organic reactions both in rate acceleration and product yield enhancement, but research on chiral arsenic compounds in asymmetric synthesis and catalysis still lacks much attention.

We designed and developed a new protocol for the synthesis of a class of novel monodentate chiral arsines, which possess the C₂-symmetric 1,1'-dinaphthyl-2,2'- bis(methylene) backbone. Details of the chiral arsine syntheses are presented in Chapter 2, including the structural characterization by X-ray crystallographic analysis. As the first application, these chiral arsines were used for stoichiometric asymmetric Wittig reactions with 4-substituted cyclohexanones. Reversal of stereochemistry caused by metal cations was observed and discussed in terms of conformational flexibility of the chiral arsonium ylides. Up to ca. 40% ee of the olefinic products was obtained.

The chiral arsines were then examined as the monodentate ligands for asymmetric carbon-carbon bond forrning reactions. Chapters 3 and 4 describe the results of Pd-catalyzed asymmetric allylic alkylation (AAA) and asymmetric Heck reaction (AHR), respectively. For AAA, up to 95% ee was obtained for the reactions of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate (rt, 4 h) and 2,4-pentanedione (75 ℃, 5 h) after optimization of reaction conditions. A 1:1 Pd complex with a bulky chiral arsine was confirmed by X-ray crystallographic analysis, which provides the basis for construction of a working model for asymmetric induction. For AHR, a number of aryl triflates was reacted with 2,3-dihydrofuran to give chiral 2-aryl-2,5-dihydrofurans as the major products with up to 96% ee. A 1:2 Pd complex with a less sterically demanding arsine was established by X-ray crystallographic analysis, which suggests a possible model of asymmetric induction via the cationic pathway.

Finally, Chapter 5 presents some preliminary results on preparation of a polymer-bound non-C₂-symmetric chiral arsine and use as the heterogeneous chiral ligand in AAA. Three rounds of recycling of the ligand were demonstrated, giving moderate (44-52%) ees for the AAA product compared to 71% ee obtained with the corresponding non-polymer-bound analog. With these encouraging results, we demonstrated that loss of C₂-symmetry in the chiral arsine ligands is not detrimental to enantioselectivity. Moreover, the feasibility of the polymer-bound chiral arsine ligand for easy recycling has been confirmed and it deserves for further investigation.