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

• Published in: Angewandte Chemie International Edition 2019-06, Vol.58 (25), p.8341-8345
• Main Authors: Yamada, Shuya, Kaneda, Takeshi, Steib, Philip, Murakami, Kei, Itami, Kenichiro
• Format: Article
• Language: English
• Subjects: 2,2′-bipyridyls; Catalysis; Chemical reactions; Chemical synthesis; C−H arylation; Dehydrogenation; dehydrogenative coupling; Dimerization; Ligands; Palladium; Pyridines; Regioselectivity; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201814701

2,2′‐Bipyridyls have been utilized as indispensable ligands in metal‐catalyzed reactions. The most streamlined approach for the synthesis of 2,2′‐bipyridyls is the dehydrogenative dimerization of unfunctionalized pyridine. Herein, we report on the palladium‐catalyzed dehydrogenative synthesis of 2,2′‐bipyridyl derivatives. The Pd catalysis effectively works with an AgI 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. Two become one: A palladium‐catalyzed dehydrogenative C2‐selective dimerization of pyridine is described. A variety of 2,2′‐bipyridyls can be prepared directly from unfunctionalized pyridine without additional pre‐halogenation or pre‐metalation steps. The reaction is applicable to a series of sterically hindered 3‐substituted pyridine derivatives and enables the concise synthesis of twisted 3,3′‐disubstituted‐2,2′‐bipyridyls, an underdeveloped class of ligands.