| The range of commercially available aryl boronic acids is increasing due to the popularity of the Suzuki-Miyauri cross coupling reaction. However, pyridyl boronic acids are of limited availability due to difficulties in preparation/isolation by conventional methods. The scope and application of a new method for the preparation pyridyl boronic acids has been shown. This method involved the Directed ortho Metalation (DoM) of pyridine derivatives with in situ boronation. This method has been used to prepare the following new pyridyl boronic acid derivatives: 3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine-2-carboxylic acid, N,N-Diethyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinamide, N,N-Diethyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-isonicotinamide, 3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine, 3-[1,3,6,2]Dioxazaborocan-2-yl-pyridine-2-carboxylic acid diethylamide, 4-[1,3,6,2]Dioxazaborocan-2-yl-N,N-diethyl-nicotinamide, 3-[1,3,6,2]Dioxazaborocan-2-yl-N,N-diethyl-isonicotinamide, Diethyl-carbamic acid 4-[1,3,6,2]dioxazaborocan-2-yl-pyridin-3-yl ester, 4-[1,3,6,2]Dioxazaborocan-2-yl-pyridine-3-sulfonic acid diethylamide, and 2-(3-Fluoro-pyridin-4-yl)-[1,3,6,2]dioxazaborocane.; As an application, this methodology was linked to the Suzuki-Miyaura cross coupling reaction to produce the following new azabiaryl compounds: 3-Phenyl-pyridine-2-carboxylic acid diethylamide, N,N-Diethyl-3-phenyl-isonicotinamide, 3-Fluoro-4-phenyl-pyridine, N,N-Diethyl-4-(3-methoxy-phenyl)-nicotinamide, and N,N-Diethyl-4-thiophen-3-yl-nicotinamide. |
