Directed ortho 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 19a-t 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 15a-c, chloro-, fluoro-, and O-carbamoyl pyridines are adapted to this method providing a range of azabiaryls (Table 2). 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 12-14 (Scheme 3) 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 2) 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 3). A comprehensive survey of pyridyl boronates, of considerable interest in contemporary heterocyclic synthetic chemistry, is given (Figure 1).
Alessi
Manlio
M
Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario K7L 3N6, Canada.
Larkin
Andrew L
AL
Ogilvie
Kevin A
KA
Green
Laine A
LA
Lai
Sunny
S
Lopez
Simon
S
Snieckus
Victor
V
D001372:Aza Compounds / Q000138:chemical synthesis*; D001895:Boron / Q000737:chemistry; D001896:Boron Compounds / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D007202:Indicators and Reagents; D008094:Lithium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000138:chemical synthesis*
D001372:Aza Compounds; D001896:Boron Compounds; D007202:Indicators and Reagents; D008670:Metals; D011725:Pyridines; D008094:Lithium; D001895:Boron