Directed <i>ortho</i> Metalation−Boronation and Suzuki−Miyaura Cross Coupling of Pyridine Derivatives:  A One-Pot Protocol to Substituted Azabiaryls^#

A general method for the synthesis of azabiaryls <b>19a</b>−<b>t</b> by a one-pot procedure involving a Directed <i>ortho</i> metalation (D<i>o</i>M)−boronation−Suzuki−Miyaura cross coupling sequence is described. Aside from the three isomeric pyridyl carboxamides <b>15a</b>−<b>c</b>, chloro-, fluoro-, and <i>O</i>-carbamoyl pyridines are adapted to this method providing a range of azabiaryls (Table ). The method has an advantage in that it avoids the recognized difficult isolation of pyridyl boronic acids and their instability toward deboronation. The efficient synthesis of hydroxypicolinamides <b>12</b>−<b>14</b> (Scheme ) by a one-pot metalation−boronation−oxidation sequence with the LDA-B(O<i>ⁱ</i>Pr)₃ <i>in situ</i> procedure that avoids self-condensation of incipient <i>ortho</i>-metalated species (Scheme ) is delineated. The conversion of azabiaryls <b>19b</b>,<b>e</b>,<b>h</b>,<b><i>l</i></b> into azafluorenones <b>20b</b>,<b>e</b>,<b>h</b>,<b><i>l</i></b> by a directed remote metalation protocol is demonstrated (Table ). A comprehensive survey of pyridyl boronates, of considerable interest in contemporary heterocyclic synthetic chemistry, is given (Figure ).