Stereoselective Synthesis of Iminosugar-C-Glycosides through Addition of Organometallic Reagents to N-tert-Butanesulfinyl Glycosylamines: A Comprehensive Study

A comprehensive study of the preparation and reactivity of N-tert-butanesulfinyl glycosylamines with simple Grignard and organo lithium reagents in batch vs. continuous flow chemistry is reported. As they readily react as latent imine equivalents with a variety of carbon nucleophiles, these carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides. A hybrid protocol, involving the addition of benzylmagnesium chloride to a (S-R)-arabinofuranosylamine substrate in flow, at room temperature, combined with a cyclization protocol in batch is also described for the first time. Of note, this semi-continuous flow process shortens the synthesis of imino-C-glycoside scaffolds to a single workday.

Automated summary

This study comprehensively investigates the preparation and reactivity of N-tert-butanesulfinyl glycosylamines with simple Grignard and organo lithium reagents in batch and continuous flow chemistry. These carbohydrate derivatives, acting as latent imine equivalents, react readily with various carbon nucleophiles, making them useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides. Additionally, a hybrid protocol combining flow addition of benzylmagnesium chloride to a (S-R)-arabinofuranosylamine substrate at room temperature with a batch cyclization protocol is introduced for the first time. Notably, this semi-continuous flow process shortens the synthesis of imino-C-glycoside scaffolds to a single workday.