Catalytic Amination of Alcohols Using Diazo Compounds under Manganese Catalysis Through Hydrogenative N‐Alkylation Reaction

Abstract

Sustainable chemical production requires fundamentally new types of catalysts and catalytic technologies. The development of coherent and robust catalytic systems based on earth‐abundant transition metals is essential, but highly challenging. Herein, we systematically explored a general hydrogenative cleavage/N‐alkylation tandem of cyclic and acyclic diazo (N=N) compounds to value‐added amines under manganese catalysis. The reaction is catalyzed by a single‐site molecular manganese complex and proceeds via tandem dehydrogenation, transfer hydrogenation, and borrowing hydrogenation strategies. Interestingly, the reaction involves abundantly available renewable feedstocks, such as alcohols, that can act as (transfer)hydrogenating and alkylating agents. The synthetic application of our approach in large‐scale pharmaceutical synthesis and easy access to highly demanding N‐CH3/CD3 derivatives are also demonstrated. Kinetic studies show that the reaction rate depends on the concentration of alcohol and Mn‐catalyst and follows fractional orders. Several selective bond activation/formation reactions occur sequentially via amine–amide metal‐ligand cooperation.

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

“…Recently, Balaraman’s group introduced a new method for N-alkylation with diazo compounds as an amine source and alcohols as alkylating agents via a tandem process using a manganese(I)-PNP pincer complex [ 47 ]. Symmetrical, unsymmetrical, and cyclic azoarenes were studied with benzyl alcohol using catalyst Mn9 (5 mol %) and t- BuOK (2 equiv) at 130 °C for 24 h in octane, resulting in the corresponding N-alkylated amines with up to 96% yield ( Scheme 19 ).…”