Abstract
The main objective of this thesis is to design and synthesize chiral Brønsted acids capable of catalyzing the functionalization of weakly basic olefins. Olefins are a particularly intriguing substrate class because while they are widely available, many being considered feedstock chemicals, they have so far eluded asymmetric organocatalysis. In our efforts to resolve this major limitation of the field, our group recently reported an intramolecular asymmetric hydroalkoxylation using highly confined and chiral Brønsted acids, imidodiphosphorimidates (IDPi), to provide enantioenriched tetrahydrofurans and tetrahydropyrans in high yields and excellent enantioselectivities. Mechanistic investigations, including computational and kinetic analyses, suggest that the reaction proceeds via a concerted, though asynchronous pathway, in which the reaction is initiated by protonation of the olefin followed by C−O bond formation. The PhD studies described herein have focused on accessing similar reactivity in intermolecular systems. Namely, in chapter 2 of this thesis, the development of an intermolecular hydroalkoxylation reaction of styrenyl olefins with oxygenated nucleophiles is described. In particular, we report the hydroalkoxylation of styrene with benzyl alcohol to afford the corresponding ether in 95% yield with a very promising enantioselectivity (er = 76.5:23.5). The reaction is tolerant of a range of nucleophilic partners, including alcohols, carboxylic acids, and phenols to yield the corresponding functionalized products with moderate degrees of enantioinduction. Our efforts to increase the enantioselectivity of these transformations through catalyst optimization are delineated. Further, we report preliminary investigations into the asymmetric hydroalkoxylation of structurally-simple olefins. In chapter 3, we report the development of a new class of highly acidic chiral catalysts, deemed imido-(N,Nʹ-bis(sulfonimidoyl))-diphorphorimidates (I2DPi’s). This development was inspired by the work of Yagupolskii, who, among others, has described dramatic increases in the acidity of neutral molecules toward superacids by substituting S=O bonds with S=NSO2CF3 (S=NTf) bonds. These novel scaffolds not only enable significantly increased reactivity in both Brønsted and Lewis acid catalysis, but uniquely provide two additional chiral handles for tuning enantioselectivity within the catalyst pocket, potentially offering new avenues in acid catalyzed transformations.
