β‑Selective C‑Arylation of Silyl Protected 1,6-Anhydroglucose with Arylalanes: The Synthesis of SGLT2 Inhibitors

The stereoselective arylation of hydroxy protected 1,6-anhydro-β-d-glucose with arylalanes to provide β-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Brønsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy...

Full description

Saved in:
Bibliographic Details
Published inJournal of organic chemistry Vol. 80; no. 4; pp. 2295 - 2309
Main Authors Henschke, Julian P, Wu, Ping-Yu, Lin, Chen-Wei, Chen, Shi-Feng, Chiang, Pei-Chen, Hsiao, Chi-Nung
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 20.02.2015
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
ORGANOALUMINUM
ALUMINUM
KETONES
ARYLALUMINUM REAGENTS
NUCLEOSIDES
OLIGOSACCHARIDE ANALOGS
POLYSACCHARIDES
ARYL
STEREOSELECTIVE-SYNTHESIS
GLYCOSYLATION
Online AccessGet full text

Cover

More Information
Summary:The stereoselective arylation of hydroxy protected 1,6-anhydro-β-d-glucose with arylalanes to provide β-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Brønsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me3Al and i-Bu2AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-3263
1520-6904
DOI:10.1021/jo502839e