ZnMe2-Mediated, Direct Alkylation of Electron-Deficient N-Heteroarenes with 1,1-Diborylalkanes: Scope and Mechanism
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- Title
- ZnMe2-Mediated, Direct Alkylation of Electron-Deficient N-Heteroarenes with 1,1-Diborylalkanes: Scope and Mechanism
- Authors
- CHO, SEUNG HWAN; HWANG, CHIWON
- Date Issued
- 2020-07-29
- Publisher
- AMER CHEMICAL SOC
- Abstract
- The regioselective, direct alkylation of electron-deficient N-heteroarenes is, in principle, a powerful and efficient way of accessing alkylated N-heteroarenes that are important core structures of many biologically active compounds and pharmaceutical agents. Herein, we report a ZnMe2-promoted, direct C2- or C4-selective primary and secondary alkylation of pyridines and quinolines using 1,1-diborylalkanes as alkylation sources. While substituted pyridines and quinolines exclusively afford C2-alkylated products, simple pyridine delivers C4-alkylated pyridine with excellent regioselectivity. The reaction scope is remarkably broad, and a range of C2- or C4-alkylated electron-deficient N-heteroarenes are obtained in good yields. Experimental and computational mechanistic studies imply that ZnMe2 serves not only as an activator of 1,1-diborylalkanes to generate (alpha-borylalkyl)methylalkoxy zincate, which acts as a Lewis acid to bind to the nitrogen atom of the heterocycles and controls the regioselectivity, but also as an oxidant for rearomatizing the dihydro-N-heteroarene intermediates to release the product.
- Keywords
- FREE REGIOSELECTIVE ALKYLATION; C-H FUNCTIONALIZATION; SELECTIVE ALKENYLATION; DIORGANOZINC COMPOUNDS; MOLECULAR CALCULATIONS; NITROGEN-HETEROCYCLES; FACILE SYNTHESIS; OXIDES; ARYLATION; METHYLATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/104103
- DOI
- 10.1021/jacs.0c06827
- ISSN
- 0002-7863
- Article Type
- Article
- Citation
- JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 142, no. 30, page. 13235 - 13245, 2020-07-29
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