A Heterogeneous‐Catalyst‐Based, Microwave‐Assisted Protocol for the Synthesis of 2,2′‐Bipyridines

Abstract

A new method to prepare 2,2'-bipyridines in short reaction times using microwave assistance and heterogeneous catalysts has been developed. Using a Negishi-like protocol, it was found that Ni/ Al 2 O 3 -SiO 2 afforded 2,2'-bipyridine products in up to 86 % yields in 1h. Palladium supported on alumina also provided comparable yields of 2,2'-bipyridines to that seen for homogeneous PEPPSI™ and tetrakis(triphenylphosphine) palladium complexes.

Reductive Couplings of 2-Halopyridines without External Ligand: Phosphine-Free Nickel-Catalyzed Synthesis of Symmetrical and Unsymmetrical 2,2′-Bipyridines

“…It clearly indicated that NiCl 2 could hardly catalyze the coupling in the absence of 2,2′-bipyridine; instead, the addition of external 2,2′-bipyridine promoted the reaction in 83% yield. Interestingly, it is generally believed that the preparation of 2,2′-bipyridines through the coupling reaction is usually more difficult relative to those of 3,3′-bipyridines, , our findings lead to the opposite conclusion: the present reductive coupling of 2-halopyridines can proceed facilely without the external ligands, leading to 2,2′-bipyridine, conversely, the coupling of 3-bromopyridines to 3,3′-bipyrdine cannot take place under the same conditions.…”

“…Transition-metal-catalyzed coupling reactions have found application in the synthesis of various biaryl compounds including arylpyridines and bipyridines; however, the preparation of 2,2′-bipyridines by these coupling reactions is usually considered to be most difficult relative to 2,3′- or 2,4′-bipyridines. , This is due to two main problems associated with 2,2′-bipyridine-forming cross-coupling reactions: (a) the coordination ability of 2,2′-bipyridines can have an inhibition effect on the catalytic cycle , and (b) the preparation of the 2-pyridyl organometallics can be problematic. To circumvent the difficulty with the 2-pyridyl organometallic preparation, Ni-catalyzed direct couplings of 2-halopyridines in the presence of reducing agents provide an alternative .…”

Microwave Assisted Suzuki-Miyaura and Ullmann Type Homocoupling Reactions of 2- and 3-Halopyridines Using a Pd(OAc)2/Benzimidazolium Salt and Base Catalyst System

“…But most of the reported synthesis require a long reaction time and provide only moderate yields. To our knowledge there is only one report of a catalytic synthesis of bipyridine under microwave irradiation using a phosphine based ligand and there is no example of palladium NHC catalyzed direct arylation using halopyridines and phenylboronic acid and homocoupling of the halopyridines under microwave heating conditions [ 52 ].…”

Environmentally benign synthesis of heterocyclic compounds by combined microwave-assisted heterogeneous catalytic approaches†

“…In a convenient synthesis of symmetrical and unsymmetrical bipyridines by cross coupling reactions Moore et al illustrated the use of heterogeneous Ni and Pd catalysts under microwaveassisted conditions (Scheme 28). 64 In the case of Ni catalysis, the This journal is © The Royal Society of Chemistry 2012 most practical conditions involved Ni/Al 2 O 3 -SiO 2 (50 mol% loading) with no phosphine ligand. Yields were moderate under Pd-catalysis; however, only 5 mol% catalyst loading was required.…”