Catalytic control over selectivity in the synthesis of glycosides and quaternary centers

Abstract

In Chapter 1, we describe the development of bis-thiourea hydrogen-bond-donor catalyzed chemo- and stereoselective b-mannosylations of phenols in the presence of alcohols, thiols, and thiophenols. Achieving chemoselective glycosylation of functionally complex phenols containing potentially competing nucleophilic sites remains challenging due to the relatively poor nucleophilicity of phenols. In this work, we explored how specific catalyst design and noncovalent interactions can enable differentiation between different classes of nucleophiles. We found that differentiation between phenols over alkyl alcohols and thiols can be achieved through a combination of matched secondary aromatic interactions and H-bonding between catalyst and nucleophile. In contrast, selectivity of phenols over more acidic thiophenols is achieved exclusively through preferential binding to the catalyst. The catalytic method described here operates under neutral reaction conditions, making it distinct and complementary to existing methods that rely on chemoselective deprotonation of phenols. In Chapter 2, we describe our ongoing efforts towards developing an enantioselective and catalytic homologation reaction to access tertiary α-chloro pinacol boronic esters from commercially available boronic esters and 1,1-dichloroethane. The synthetic utility of these intermediate products as chiral building blocks is investigated through sequential stereospecific elaborations of both the halogen and boronic ester to access tertiary alcohols in high enantiomeric excess. We present efforts to enhance the yield and enantioselectivity of this reaction, achieving up to 52% yield with 87% ee. Enantioselectivities as high as 92% were observed in reactions with lower yields.