Syntheses and Application of New Chiral Phosphines as Ligands and Catalysts

Chiral phosphines are central to the development of enantioselective organic transformations because they are used extensively as ligands or organocatalysts. The work presented in this thesis describes efforts to develop new phosphine ligands, either through supramolecular self-assembly or through novel synthetic methods. Chapter 1 describes the development of chiral phosphines that self-assemble through reversible covalent iminoboronate linkages. By utilizing a facile condensation process driven by an intramolecular B–N interaction, a 100-ligand library was generated. Incorporation of various 2-formylarylboronic acids, chiral aminophosphines and vicinal diols, resulted in phosphine ligands with great structural diversity. The self-assembled ligands were employed in transition metal-catalyzed enantioselective transformations. Likely coordination modes and ligand decomposition pathways in the presence of transition metals are discussed. Synthesis of chiral beta-aminophosphines possessing different diarylphosphino moieties is presented in Chapter 2. The protocol made use of the nucleophilic ring-opening of sulfamidates derived from serval optically pure amino alcohols. Through the use of phosphine oxides as ‘masked’ phosphine equivalents, purification and isolation of intermediates from otherwise challenging synthetic steps were made possible. P- versus O-alkylation in the reactions of diarylphosphinites with sulfamidates will also be discussed. ii Chapter 3 describes an extension of the synthesis of beta-aminophosphines described in Chapter 2 to P-chiral variants. Treatment of an enantiopure sulfamidate with a racemic unsymmetrical secondary phosphine oxide resulted in diastereomeric intermediates that could be separated either by fractional recrystallization or silica gel chromatography. A BH3-mediated stereospecific phosphine oxide reduction was developed and implemented to convert these adducts to the corresponding diastereomerically enriched beta-aminophosphines. Finally, Chapter 4 describes the application of the thiourea derivatives of these P-chiral aminophosphines as organocatalysts. Evaluation of their catalytic performance in enantioselective Morita-Baylis-Hillman reactions revealed that the P-chiral catalysts afforded superior levels of selectivity compared to the non-P-chiral variant. Additionally, the spatial disposition of the two different P-aryl groups was found to influence catalytic activity as a result of matching/mismatching effects.Ph.D