Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance
Thibaud Brégent, Maria V. Ivanova, Thomas Poisson, Philippe Jubault, Julien Legros
Abstract
Abstract We describe herein the first halogen dance (HD) in continuous flow on 2‐chloro‐3‐bromopyridine by selectively trapping a (pyridin‐4‐yl)lithium species that is known to undergo the halogen‐dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. The HD process was extended to fluoro‐iodopyridines by using various electrophiles to afford 28 examples with yields ranging from 42 to 97 % with very short residence times. Finally, scale up of the reaction was demonstrated, affording a promising space‐time yield (STY) of 4.2 kg.h −1 .L −1 .
Topics & Concepts
HalogenElectrophileDanceYield (engineering)Continuous flowChemistryLithium (medication)Residence time (fluid dynamics)Medicinal chemistryMaterials scienceOrganic chemistryArtCatalysisPhysicsMetallurgyPsychologyMechanicsVisual artsEngineeringGeotechnical engineeringPsychiatryAlkylInnovative Microfluidic and Catalytic Techniques InnovationNanomaterials for catalytic reactionsAsymmetric Hydrogenation and Catalysis