Dehydrogenative Synthesis of 2,2′‐Bipyridyls through Regioselective Pyridine Dimerization

Abstract

2,2'-Bipyridyls have been utilized as indispensable ligands in metal-catalyzed reactions.T he most streamlined approach for the synthesis of 2,2'-bipyridyls is the dehydrogenative dimerization of unfunctionalized pyridine.H erein, we report on the palladium-catalyzed dehydrogenative synthesis of 2,2'-bipyridyl derivatives.The Pd catalysis effectively works with an Ag I salt as the oxidant in the presence of pivalic acid. A variety of pyridines regioselectively react at the C2-positions. This dimerization method is applicable for challenging substrates such as sterically hindered 3-substituted pyridines, where the pyridines regioselectively react at the C2-position. This reaction enables the concise synthesis of twisted 3,3'disubstituted-2,2'-bipyridyls as an underdeveloped class of ligands.

Geometric and electronic effects on the performance of a bifunctional Ru2P catalyst in the hydrogenation and acceptorless dehydrogenation of N-heteroarenes

“…In particular, 2,2'-biquinoxaline was formed upon hydrogenation of quinoxaline in the presence of Ru2P/AC, except for the product 1,2,3,4-tetrahydro-quinoxline (Table 3). This out- come may be attributed to the dehydrogenative dimerization of quinoxaline, which is the most straightforward and attractive route [49][50][51][52][53]. The tetrahydro-quinoxaline product (4a) was obtained in 9.1% yield under 10 bar H2 atmosphere at 60 °C using the Ru2P/AC catalyst, while 5a was detected in 6.1% yield.…”

Recent Advances in the Synthesis of 2,2′-Bipyridines and Their Derivatives

“…A further advancement to the area was reported recently by Yamada et al (Scheme 11). 34 The optimized catalytic system consisted of palladium acetate (10 mol%) and silver pivalate serving as a stoichiometric oxidant; pivalic acid was shown to accelerate product formation and improved the regioselectivity of the coupling. Notably, only trace amounts of isomeric 3,3′-bipyridines were observed.…”

Synthesis of 2,2’‐Bipyridines through Catalytic C−C Bond Formations from C−H Bonds

“…[15] In 2019 Murakami, Itami and co-workers have developed a general and practical method for synthesizing 2,2'-bipyridines in high yields using Pd-catalyzed dehydrogenative coupling pyridine (Scheme 3). [16] The reaction was performed using 5 mol % Pd(OAc) 2 in the presence of AgOPiv as base/oxidant in CPME (cyclopentyl methyl ether) at 140 °C. Interestingly, under these conditions, the dimerization of pyridine occurred in 80 % yield.…”