Organic Chemistry Portal

Abstracts

Search:

Merging Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Suzuki-Miyaura-Type Cross-Coupling of Alkyl Iodides and Organoborons

Zhenhua Zhang, Bartosz Górski and Daniele Leonori*

*Department of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, U.K., Email: daniele.leonorirwth-aachen.de

Z. Zhang, B. Górski, D. Leonori, J. Am. Chem. Soc., 2022, 144, 1758-1765.

DOI: 10.1021/jacs.1c12649 (free Supporting Information)


see article for more reactions

Abstract

A mechanistically distinct approach achieves Suzuki-Miyaura-type cross-couplings between alkyl iodides and aryl organoborons. This process requires a copper catalyst but the activation of the alkyl electrophile is based on the halogen-atom-transfer ability of α-aminoalkyl radicals to convert secondary alkyl iodides into the corresponding alkyl radicals that then couple with the boronate species.

see article for more examples

proposed mechanism



Preparation of cumOOTMS

A round bottom flask equipped with a stirring bar was charged with Et3N (10.5 mL, 75.0 mmol) and hexane (100 mL). Cumene hydroperoxide (9.3 mL, 80% technical solution, 50.0 mmol) was slowly added. The reaction media was then cooled in an ice-water bath and TMSCl (8.25 mL, 65.0 mmol) was slowly added. When the addition was completed, the ice-water bath was removed and the reaction was let stirring at room temperature. After 1 hour, H2O (100 mL) was added. The layers were separated and the organic phase was washed with H2O (100 mL x 4) and brine (100 mL), dried (MgSO4), filtered and evaporated to give cumOOTMS as an oil (10.97 g, 98%) with approx density of 0.94 g/mL.

Stability studies of cumOOTMS: CumOOTMS does not have explosion propagating property and can be used on scale.

General Procedure for the Boronate Preparation

An oven-dry tube equipped with a stirring bar was charged with the boronic ester (1.1 equiv.). The tube was capped with a Supelco aluminium crimp seal with septum (PTFE/butyl), evacuated and refilled with N2 (x 3). Dry and degassed THF (0.5 M) was added and the tube was cooled to -78 °C. n-BuLi (1.0 equiv., 2.5 M in hexanes) was added dropwise and after 1 minute the cooling bath was removed and the stirring was continued for 1 h. The THF solution of the boronate was directly used in the coupling reactions.

General Procedure for the C-C Coupling Reaction

An oven-dry tube equipped with a stirring bar was charged with the alkyl iodide (0.10 mmol, 1.0 equiv) and [Cu(MeCN)4]PF6 (7.5 mg, 0.020 mmol, 20 mol%). The tube was capped with a Supelco aluminium crimp seal with septum (PTFE/butyl), evacuated and refilled with N2 (x 3). Dry and degassed DMSO (1.0 mL), TMHD (5.2 μL, 0.025 mmol, 25 mol%), NEt3 (42 μL, 0.30 mmol, 3.0 equiv.) and the boronate (0.5 mL, 0.25 mmol, 2.5 equiv., 0.5M in THF) were sequentially added. cumOOTMS (67 mg, 72 μL, 0.30 mmol, 3.0 equiv.) was added dropwise to the vigorously stirred solution. Stirring was continued for 1 h, then NH4Cl sat. (20 mL), EtOAc (20 mL) were added. The organic layer was separated and the aqueous layer was extracted with EtOAc (15 mL x 2). The combined organic phases were washed with water (20 mL), brine (20 mL), dried (MgSO4), filtered, and evaporated. The crude mixture was purified by flash column chromatography on silica gel.


Key Words

azetidines, cumene hydroperoxide


ID: J48-Y2022