Transition metal-free catalytic reduction of primary amides using an abnormal NHC based potassium complex: integrating nucleophilicity with Lewis acidic activation.

Mrinal Bhunia,Sreejyothi P,Swadhin K Mandal,Jasimuddin Ahmed,Arpan Das,Sumeet Ranjan Sahoo

doi:10.1039/c9sc05953a

Mrinal Bhunia, Sreejyothi P + Show 4 more

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An abnormal N-heterocyclic carbene (aNHC) based potassium complex was used as a transition metal-free catalyst for reduction of primary amides to corresponding primary amines under ambient conditions. Only 2 mol% loading of the catalyst exhibits a broad substrate scope including aromatic, aliphatic and heterocyclic primary amides with excellent functional group tolerance. This method was applicable for reduction of chiral amides and utilized for the synthesis of pharmaceutically valuable precursors on a gram scale. During mechanistic investigation, several intermediates were isolated and characterized through spectroscopic techniques and one of the catalytic intermediates was characterized through single-crystal XRD. A well-defined catalyst and isolable intermediate along with several stoichiometric experiments, in situ NMR experiments and the DFT study helped us to sketch the mechanistic pathway for this reduction process unravelling the dual role of the catalyst involving nucleophilic activation by aNHC along with Lewis acidic activation by K ions.

Highlights

Amines belong to a privileged class of compounds, routinely present in many ne and bulk chemicals, drugs, agrochemicals, dyes, surfactants, detergents and organic materials.[1,2,3,4,5,6] One of the most attractive methods for synthesis of amines is the deoxygenative reduction of amides.[7]
We have achieved the reduction of primary amides to amines through deoxygenative hydroboration exploiting an abnormal N-heterocyclic carbene based potassium complex[34] (1) under ambient conditions in which the catalyst acts by integrating the nucleophilicity of weakly bound aNHC and Lewis acidic activation imparted by the K ions
Only KN(SiMe3)[2] failed to afford any reduction product. These results clearly suggest that combination of KN(SiMe3)[2] and aNHC is accountable for reduction of primary amides

Summary

Introduction

Amines belong to a privileged class of compounds, routinely present in many ne and bulk chemicals, drugs, agrochemicals, dyes, surfactants, detergents and organic materials.[1,2,3,4,5,6] One of the most attractive methods for synthesis of amines is the deoxygenative reduction of amides.[7]. Aluminum hydride or sodium borohydrides are unattractive in terms of atom economy and environmental issues They suffer from safety and selectivity of the process generating a stoichiometric amount of inorganic waste.[7] In contrast, atom economical catalytic hydrogenation of primary amides is highly desirable and to date no example of catalytic hydrogenation of primary amides has been reported (Scheme 1).[26]. We have achieved the reduction of primary amides to amines through deoxygenative hydroboration exploiting an abnormal N-heterocyclic carbene (aNHC) based potassium complex[34] (1) under ambient conditions in which the catalyst acts by integrating the nucleophilicity of weakly bound aNHC and Lewis acidic activation imparted by the K ions. We posed a question, whether a weakly bound N-heterocyclic carbene (NHC) in the form of its potassium complex is able to utilize its s-donating (nucleophilic) properties in activating a hydride transfer reagent (such as borane) to reduce primary amides in a catalytic fashion. We probed reduction of primary amides in the presence of sterically encumbering groups such as 2,6-dimethoxybenzamide, 2,6di uorobenzamide, 2-methyl-3-chlorobenzamide, and 2methyl-5- uorobenzamide which rendered very good yields

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Conclusions

51 Crystal data for 1a