Efficient Procedure for Reductive Opening of Sugar 4,6-O-Benzylidene Acetals in a Microfluidic System

Abstract

An efficient procedure for the reductive opening of 4,6-O-benzylidene acetals was established under microfluidic conditions. 4,6-O-Benzylidene acetals of the glucose, glucosamine, and galactose derivatives were selectively converted into the corresponding 4- or 6-O-benzyl derivatives in nearly quantitative yields.

microfluidic system - reductive opening - 4,6-O-benzylidene acetal - oligosaccharides

References and Notes

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Microfluidic Reaction; Typical Procedure: A solution of BF₃·OEt₂ (3 mL, 23.7 mmol, 1.0 M) in CH₂Cl₂ (23.7 mL) was injected in advance to the micromixer by using a syringe pump at a flow-rate of 0.5 mL/min. Subsequently, a solution of benzylidene acetal 1 (1 g, 2.69 mmol, 0.1 M) and Et₃SiH (4.3 mL, 26.9 mmol, 1.0 M) dissolved in CH₂Cl₂ (26.9 mL) was also injected to the micromixer by another syringe pump at the flow rate of 0.5 mL/min and mixed at 0 °C. After the reaction mixture was allowed to flow at r.t. for an additional 45 s through a Teflon reactor tube (Φ = 1.0 mm, l = 0.9 m), the mixture was quenched by pouring it to a sat. NaHCO₃ solution at 0 °C. It took about 7 min to consume 1 g of the substrate 1 under above conditions. The mixture was extracted with EtOAc, washed with brine, dried over Na₂SO₄, filtered, and concentrated in vacuo to give the crude product. The residue was purified by preparative TLC on silica gel (50% EtOAc in hexane) to afford 5 (935 mg, 93%). The conditions established herein can be readily applied to the scale-up synthesis simply by preparing the stock solutions of substrate and reagents and pumping them continuously into the micromixer.