Development of an Efficient Process to Prepare Methyl 4,5,6-Trichloropicolinate Using Highly Selective C–H Borylation/Chlorodeborylation Reactions

This report details the development of an efficient process to prepare methyl 4,5,6-trichloropicolinate using Ir-catalyzed C–H borylation followed by CuCl₂-mediated chlorodeborylation under optimized conditions. The process featured extremely low loadings (as low as 0.0005 equiv) of an [Ir(OMe)cod]₂ precatalyst with outstanding reactivity and regioselectivity (>150:1) during C–H borylation. The impurity from product dechlorination can be significantly reduced by >30-fold to <0.4%. The excellent reactivity and control of the protodeborylation impurity in subsequent copper-mediated chlorodeborylation was also highlighted. This enabled successful demonstration of a highly efficient process at a 46 mmol scale with an excellent overall yield (75%). Furthermore, it was showcased that the Ir catalyst and 4,4′-di-tert-butyl-2,2′-bipyridyl (dtbpy) ligand can be directly recycled and reused after filtration of the product. All these developments would offer significant economic benefits as well as process simplification for applying Ir chemistry.