Cooperative Brønsted Acid-Type Organocatalysis for the Stereoselective Synthesis of Deoxyglycosides.

Carlos Palo-Nieto,Ryan Williams,Abhijit Sau,M Carmen Galan

doi:10.1021/acs.joc.6b02498

Carlos Palo-Nieto, Ryan Williams + Show 2 more

Open Access

https://doi.org/10.1021/acs.joc.6b02498

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Journal: Journal of Organic Chemistry	Publication Date: Dec 22, 2016
Citations: 58	License type: cc-by

Affiliation: University of Bristol

Abstract

A practical approach for the α-stereoselective synthesis of deoxyglycosides using cooperative Brønsted acid-type organocatalysis has been developed. The method is tolerant of a wide range of glycoside donors and acceptors, and its versatility is exemplified in the one-pot synthesis of a trisaccharide. Mechanistic studies suggest that thiourea-induced acid amplification of the chiral acid via H-bonding is key for the enhancement in reaction rate and yield, while stereocontrol is dependent on the chirality of the acid.

Highlights

Cooperative catalysis between thioureas and Brønsted acids, whereby the enhanced catalytic activity of the thiourea acts as an acid amplifier, has successfully been applied to asymmetric catalysis,[1] and more recently, reports have emerged from the Schmidt group applying this type of synergistic catalysis to glycosylation reactions involving O-glycosyl trichloroacetimidate donors to yield β-selective glycosides.[2]
Acid-catalyzed direct nucleophilic substitution on a glycal is one of the most widely used and efficient methods for their synthesis, these reactions often give anomeric mixtures and side products (e.g., Ferrier rearrangement side-products).4e,4r,5 As part of our ongoing interest in developing stereoselective glycosylation methods,[6] we decided to focus our attention on the synthesis of deoxyglycosides
The reaction is widely applicable to a range of glycosyl donors and nucleophile acceptors, proceeds with excellent yields and high selectivity for the α-anomer, and is tolerant of most common protecting groups

Summary

■ INTRODUCTION

Cooperative catalysis between thioureas and Brønsted acids, whereby the enhanced catalytic activity of the thiourea acts as an acid amplifier, has successfully been applied to asymmetric catalysis,[1] and more recently, reports have emerged from the Schmidt group applying this type of synergistic catalysis to glycosylation reactions involving O-glycosyl trichloroacetimidate donors to yield β-selective glycosides.[2]. Thiourea 1 was chosen as the organocatalyst based on previous successful work from our group and others.1a,b,2,7,8 BINOL-derived phosphoric acids have been shown to be effective in many asymmetric transformations,[9] including some success in glycosylations involving trichloroacetimidate glycoside donors.[10] More recently, chiral phosphoric acids have been shown to catalyze the spiroketalization of cyclic enol ethers bearing a pendant alcohol nucleophile in a highly diastereoselective syn-selective concerted mechanism whereby the phosphoric acid acts as a bifunctional catalyst activating both the alkene and alcohol nucleophile.[11]

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ REFERENCES