Development of Photoredox Cross-Electrophile Coupling of Strained Heterocycles with Aryl Bromides Using High-Throughput Experimentation for Library Construction
Yukiko Mori, Mutsuyo Hayashi, Ryuma Sato, Kuninori Tai, Tsuyoshi Nagase
Abstract
Microscale high-throughput experimentation was used to develop a photoredox-assisted reductive cross-coupling reaction of aryl halides with strained aliphatic heterocycles facilitated via a ring-opening reaction. This methodology was found to be applicable to medicinally relevant substrates including Boc-protected strained aliphatic heterocycles and (hetero)aryl bromides and was used for compound library construction via parallel medicinal chemistry. Furthermore, the coupling reactions were shown to be scalable to the gram scale by continuous flow reaction. A possible reaction mechanism is also discussed.
Topics & Concepts
ChemistryArylElectrophileCombinatorial chemistryMicroscale chemistryCoupling reactionHalideThroughputCoupling (piping)Photoredox catalysisOrganic chemistryComputational chemistryCatalysisAlkylComputer sciencePhotocatalysisMaterials scienceWirelessTelecommunicationsMathematics educationMathematicsMetallurgyRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsInnovative Microfluidic and Catalytic Techniques Innovation