Continuous Flow-Enabled Synthesis of Bench-Stable Bicyclo[1.1.1]pentane Trifluoroborate Salts and Their Utilization in Metallaphotoredox Cross-Couplings
Michael D. VanHeyst, Ji Qi, Anthony J. Roecker, Jonathan M. E. Hughes, Lili Cheng, Zheyu Zhao, Jingjun Yin
Abstract
Bicyclo[1.1.1]pentane motifs have gained increasing popularity in medicinal chemistry as bioisosteres because of their ability to impact key physicochemical properties. However, reports of direct C(sp2)–C(sp3) cross-coupling of these fragments to afford biaryl isosteres have been scarce. Herein we describe the development of continuous flow-enabled synthesis of bench-stable bicyclo[1.1.1]pentane trifluoroborate salts. Furthermore, we demonstrate the use of metallaphotoredox conditions to enable cross-coupling of these building blocks with complex aryl halide substrates.
Topics & Concepts
ChemistryPentaneHalideBicyclic moleculeContinuous flowArylCombinatorial chemistryCoupling (piping)Organic chemistryBiochemical engineeringAlkylMaterials scienceMetallurgyEngineeringRadical Photochemical ReactionsInnovative Microfluidic and Catalytic Techniques InnovationCatalytic C–H Functionalization Methods