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Chan-Lam Amination of Secondary and Tertiary Benzylic Boronic Esters

James D. Grayson, Francesca M. Dennis, Craig C. Robertson and Benjamin M. Partridge*

*Department of Chemistry, University of Sheffield, Dainton Building, Sheffield S3 7HF, United Kingdom, Email: b.m.partridgesheffield.ac.uk

J. D. Grayson, F. M. Dennis, C. C. Robertson, B. M. Partridge, J. Org. Chem., 2021, 86, 9883-9897.

DOI: 10.1021/acs.joc.1c00976 (free Supporting Information)



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Abstract

A Chan-Lam coupling reaction of benzylic and allylic boronic esters with primary and secondary anilines provides valuable alkyl amine products. Both secondary and tertiary boronic esters can be used as coupling partners, with mono-alkylation of the aniline occurring selectively.

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Experimental Procedure for the Cu-Promoted Amination of Alkylboronic Esters

Preparative Scale Cu-Catalyzed Amination of Alkylboronic Esters

A flask containing the corresponding boronic ester (0.50 mmol, 1 equiv), aniline (2.00 mmol, 4 equiv), Cu(OAc)2 (0.182 g, 1.00 mmol), and Cs2CO3 (0.0820 g, 0.252 mmol) was purged with argon. Methanol (1.0 mL) and pyridine (0.33 mL) were added, and the mixture was stirred at 50 or 65 C until the reaction was complete (as determined by TLC). The mixture was cooled to room temperature, NH4OH (10 mL) was added, and the mixture was extracted with Et2O (3 10 mL), dried (MgSO4), filtered, and concentrated in vacuo. The crude material was purified by column chromatography.

Preparative Scale Cu-Catalyzed Amination of Alkylboronic Esters with Oxidative Workup

A flask containing the corresponding boronic ester (0.50 mmol, 1 equiv), aniline (2.00 mmol, 4 equiv), Cu(OAc)2 (0.182 g, 1.00 mmol), and Cs2CO3 (0.082 g, 0.25 mmol) was purged with argon. Methanol (1.0 mL) and pyridine (0.33 mL) were added, and the mixture was stirred at 50 or 65 C until the reaction was complete (as determined by TLC). The mixture was cooled to room temperature, NH4OH (10 mL) was added, and the mixture was extracted with Et2O (3 10 mL), dried (MgSO4), filtered, and concentrated in vacuo. THF (1 mL), H2O (1 mL), and sodium perborate (0.382 g, 2.50 mmol) were added, and the mixture was stirred at RT for 1 h. The mixture was diluted with H2O (10 mL) and extracted with EtOAc (3 10 mL). The combined organic phases were dried (MgSO4), filtered, and concentrated in vacuo. The crude material was purified by column chromatography.


Key Words

Chan-Lam Coupling, Aryl Amines, Benzyl Amines, Copper Salts


ID: J42-Y2021