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Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones as Amidating Reagents

Noah Wagner-Carlberg and Tomislav Rovis*

*Department of Chemistry, Columbia University, New York, New York 10027, United States, Email: tr2504columbia.edu

N. Wagner-Carlberg, T. Rovis, J. Am. Chem. Soc., 2022, 144, 22426-22432.

DOI: 10.1021/jacs.2c10552



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Abstract

Rh(III) catalyzes an intermolecular anti-Markovnikov hydroamidation of unactivated alkenes with dioxazolone amidating reagents and isopropanol as hydride source under mild conditions. The reaction tolerates a wide range of functional groups and efficiently converts also electron-deficient, styrenes, and 1,1-disubstituted alkenes to their corresponding linear amides.

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proposed mechanism



General Procedure for Hydroamidation of Alkenes

To a 1.5-dram vial with magnetic stir bar were added 3.6 mg [Cp*CF3RhCl2]2 (0.005 mmol, 5 mol%), and 15.2 mg K2CO3 (0.11 mmol, 1.1 equiv.) under air. To a second 1.5-dram vial were added alkene (0.1 mmol, 1 equiv.) and dioxazolone* (0.5 mmol, 5 equiv.) under air. In an argon atmosphere glovebox, the alkene and dioxazolone were dissolved in 200 L of dry DCE, and the resulting solution was transferred to the vial containing [Cp*CF3RhCl2]2 and K2CO3. 50 L of dry i-PrOH were then added to this vial, and it was sealed by a screw cap with PTFE septum. Soon after the addition of i-PrOH, the reaction mixture darkened in color to a deep red. The vial was removed from the glovebox and heated to 70 C in a heating block for two hours, with stirring. The reaction was then removed from heat and quenched by the addition of about 1 mL of EtOAc. Successful reactions generally exhibited pressure buildup due to the evolution of CO2. This solution was filtered through a short celite plug, and the vial was rinsed with two further 1 mL portions of EtOAc that were also filtered through the plug. The plug was then flushed with one final portion of EtOAc. The filtrate was concentrated by rotary evaporator and a crude 1H NMR spectrum was taken using CDCl3 as solvent and 0.1 mmol mesitylene as internal standard. Purification of the products was carried out using Teledyne Isco Lumen CombiFlash, and 4 g RediSep Rf Disposable Flash columns. Hexanes/EtOAc or hexanes/acetone was used as eluent, and linear gradients from pure hexanes to the desired solvent ratio were generally used.

*Note: dioxazolones that are solid at room temperature were instead weighed into the vial containing [Cp*CF3RhCl2]2 and K2CO3.


Key Words

protected primary amines, amides, isopropanol


ID: J48-Y2022