Continuous flow-ultrasonic synergy in click reactions for the synthesis of novel 1,2,3-triazolyl appended 4,5-unsaturated l-ascorbic acid derivatives

Abstract

A combination of flow chemistry and batch-based synthetic procedures has been successfully applied to the assembly of novel 4,5-unsaturated l-ascorbic acid series 6a-6n with diverse C-6-substituted 1,2,3-triazole moiety. We report herein the first Cu(i)-catalyzed 1,3-dipolar cycloaddition of azido functionalized l-ascorbic acid derivative and selected alkynes to provide target 1,2,3-triazolyl appended 4,5-didehydro-5,6-dideoxy-l-ascorbic acid library 6a-6n under both micro-flow and batch conditions. Implementation of ultrasound with flow chemistry accelerated hour-scale reaction conditions in batch to the minute range in micro-flow device and considerably improved the yields for the flow syntheses of 6a-6n. Moreover, the synergistic use of microreactor technology and ultrasonic irradiation highlights the sustainable eco-friendly aspect of utilized method.