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

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journal contribution
posted on 02.03.2007, 00:00 by Manlio Alessi, Andrew L. Larkin, Kevin A. Ogilvie, Laine A. Green, Sunny Lai, Simon Lopez, Victor Snieckus
A general method for the synthesis of azabiaryls 19at by a one-pot procedure involving a Directed ortho metalation (DoM)−boronation−Suzuki−Miyaura cross coupling sequence is described. Aside from the three isomeric pyridyl carboxamides 15ac, chloro-, fluoro-, and O-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 1214 (Scheme ) by a one-pot metalation−boronation−oxidation sequence with the LDA-B(OiPr)3 in situ procedure that avoids self-condensation of incipient ortho-metalated species (Scheme ) is delineated. The conversion of azabiaryls 19b,e,h,l into azafluorenones 20b,e,h,l 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 ).