Directed Deprotonation−Transmetalation as a Route to Substituted Pyridines

Abstract

Regioselective C-4 deprotonation of 3-bromopyridine, followed by Li/Zn transmetalation and Pd-mediated coupling processes, provides a flexible entry to 4-substituted and 3,4-disubstituted pyridines. Application of a similar sequence to 2-bromopyridine (with LDA as base) provides 2,3-disubstituted pyridines, but using lithium 2,2,6,6-tetramethylpiperidide (LiTMP) provides access to both the 2,3- and 2,4-disubstituted isomers.

Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library

“…Installation of boronates onto oligonucleotides by Suzuki coupling has been shown previously 22 23 , including in the context of encoded libraries 24 . We adapted procedures commonly used for Suzuki coupling under aqueous conditions 25 26 27 . After completion of the final step, the wells were pooled and the library purified by reverse-phase HPLC.…”

Recent applications of the Suzuki–Miyaura cross-coupling reaction in organic synthesis

“…Similarly, Gallagher reported the synthesis of the 2,3-disubstituted pyridine 67 from 2-bromopyridine. 133 The PdCl 2 (dppf)-and Pd(PPh 3 ) 4 -catalysed reactions of 4-pyridylboronic acid with the corresponding bromides gave 68, which can furnish pyridine-substituted salicylaldehydes on further functional group transformations. 134 The reaction of carboxybenzeneboronic acid with heteroaryl bromides and chlorides gave the heteroaryl benzoic acids 69 in moderate to good yields.…”

Review. Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange

“…Negishi cross-coupling of 22 with aryl halides such as 4-nitrophenyl iodide produces the 4-arylated pyridine 23 in 78 % yield. The remaining bromide in pyridine 23 can be used for the performance of a subsequent Suzuki cross-coupling reaction (Scheme 6) [28,29].…”