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Synthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki–Miyaura Coupling
Author(s) -
Takahashi Yusuke,
Ashikari Yosuke,
Takumi Masahiro,
Shimizu Yutaka,
Jiang Yiyuan,
Higuma Ryosuke,
Ishikawa Susumu,
Sakaue Hodaka,
Shite Ibuki,
Maekawa Kei,
Aizawa Yoko,
Yamashita Hiroki,
Yonekura Yuya,
Colella Marco,
Luisi Renzo,
Takegawa Toshihiro,
Fujita Chiemi,
Nagaki Aiichiro
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901729
Subject(s) - borylation , chemistry , biphenyl , boron , combinatorial chemistry , group (periodic table) , component (thermodynamics) , suzuki reaction , coupling (piping) , organic chemistry , catalysis , palladium , aryl , thermodynamics , mechanical engineering , alkyl , physics , engineering
In a flow microreactor, aryllithiums bearing a piperidylmethyl group were generated using n BuLi by precise residence time control and effective temperature control, and then selectively borylated with boronic esters such as 2‐isopropoxy‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane (BpinO i Pr) and trimethyl borate B(OMe) 3 by fast mixing. Moreover, the direct integration with Suzuki–Miyaura cross coupling were successfully achieved to obtain nitrogen‐containing biaryl compounds. The present method could be applied for the straightforward synthesis of the key intermediate of a bioactive component bearing a piperidylmethyl‐biphenyl framework.