Synthesis of Biaryls Having a Piperidylmethyl Group Based on Space Integration of Lithiation, Borylation, and Suzuki–Miyaura Coupling. Issue 5 (29th January 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: European journal of organic chemistry. Issue 5(2020)
• Page Start: 618
• Page End: 622
• Publication Date: 2020-01-29
• Subjects: Borylation -- Flow microreactors -- Lithiation -- Piperidylmethyl groups -- Cross‐coupling; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201901729
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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. Abstract : A flow microreactor enabled the generation of aryllithiums bearing a piperidylmethyl group and their selective borylation with boronic esters. Moreover, lithiation, borylation, and Suzuki–Miyaura cross‐coupling were integrated to obtain nitrogen‐containing biaryl compounds such as a synthetic intermediate of a compound with histone deacetylase (HDAC) inhibitory activity.