Application of the Photoredox Coupling of Trifluoroborates and Aryl Bromides to Analog Generation Using Continuous Flow

Abstract

A method for the coupling of aryl bromides with potassium alkyl trifluoroborates, via nickel/photoredox dual catalysis, has been developed for use in continuous flow. This operationally simple protocol is able to form Csp-Csp bonds with significantly reduced reaction times and a broader substrate scope than when conducted in batch. The utility of this method for rapid analog synthesis has been demonstrated by the synthesis of a small library of alkyl-substituted quinazolines.

Synergistic Photoredox/Transition‐Metal Catalysis for Carbon–Carbon Bond Formation Reactions

“…Finally, alkyl‐aryl cross‐coupling reaction using organotrifluoroborates as radical precursors can be adapted in continuous flow methodologies, widening the chemical scope, increasing the reaction yields and reducing the reaction time too. Several examples were reported by Boyd and co‐workers in order to couple secondary alkyltrifluoroborates with (hetero)aryl bromides . Further developments led to a successful coupling of primary alkyl radical as well, via silicates radical precursors .…”

A Laser Driven Flow Chemistry Platform for Scaling Photochemical Reactions with Visible Light

“…13,14 Reactors of this type have been applied across academia and industry with excellent success for gram-scale reactions. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] However, extension of these plug flow reactors to kilogram-scale production remains a significant challenge. One approach that has been pursued involves increasing the number of identical reactors operating in parallel, thereby increasing the overall throughput.…”

A 3D-Printed Open Access Photoreactor Designed for Versatile Applications in Photoredox- & Photoelectrochemical Synthesis

“…[4a, 16] With the 3D-printed photoreactor the same results as with the integrated photoreactor were obtained with a yield of 86% after 8.5 h. Flow: The flow unit was tested using the sp 2sp 3 cross coupling method using trifluoroborates and aryl bromides (Scheme 5) from the Boyd lab at Vertex Pharmaceuticals Incorporated. [17] They used the Vapourtec E-series UV-150 device with a capacity of 10 ml. At a flow rate of 0.25 ml/min the residue time was 40 min and a yield of 62% was achieved.…”