Continuous-Flow Divergent Lithiation of 2,3-Dihalopyridines: Deprotolithiation versus Halogen Dance |
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Authors: | Dr Thibaud Brégent Dr Maria V Ivanova Prof?Dr Thomas Poisson Prof?Dr Philippe Jubault Dr Julien Legros |
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Institution: | Normandie Univ., INSA Rouen, UNIROUEN, CNRS, COBRA (UMR 6014), 76000 Rouen, France |
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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. |
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Keywords: | continuous flow flash chemistry halogen dance lithiation pyridines |
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