Direct Catalytic Hydrogenation of Simple Amides: A Highly Efficient Approach from Amides to Amines and Alcohols

Abstract

A highly chemoselective and reactive direct catalytic reduction of various amides to amines and alcohols was developed by using a tetradentate ruthenium complex. The catalytic system showed excellent activity (turnover numbers up to 19 600) and great functional group tolerance under mild reaction conditions, compared to several bidentate and tridentate ruthenium-catalyzed systems.

Multifaceted catalytic hydrogenation of amides via diverse activation of a sterically confined bipyridine–ruthenium framework

“…In the meantime, remarkably high TON of 8800 was observed in the hydrogenation of 3a catalyzed by a ( P , N py , N H, P )Ru complex, albeit with much higher P H2 ( P H2  = ca. 5 MPa, t  = 20 h) 36 .

Figure 2Precatalysts tested and diverse catalysts derived from 1a . ( a ) Hydrogenation of 3a using different Ru-complexes 1a – f and 2a ([Ru] 0  = 3.3 mM) as precatalysts.

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“…In any event, the H 2 -adsorption site with bulky i Pr (or Cy) groups is non-innocent and undergoes meaningful structural changes via multiple hydrogen additions before producing the diverse, active forms of catalyst. These results further suggest that a Ru complex bearing a ( P ,( N , N ) bpy , P ) ligand is more versatile and robust in the production of diverse catalysts than Ru precatalysts bearing simple bidentate ( P , N py ) 38, 40 and ( P , N H) 18–21, 26–28, 37 , tridentate ( P ,( N , N ) bpy ) 22–25 , and tetradentate ( P , N py , N H, P ) 36 ligand(s).…”

“…Unfortunately, however, those metal complexes hydrogenate majorly a range of strongly or moderately activated amides, including N -aryl-, N -acyl-, N -(di)methyl-, and α-alkoxy amides and morpholino ketones, as well as relatively simple and small amides (e.g., formamides, acetamides, trifluoroacetamides). Very recently, Zhang 36 reported an extremely active ( P , N py , N H, P )Ru catalyst that hydrogenates, in most cases, activated amides, where a rather low hydrogenation temperature (100 °C) was only tested. Mashima 37 reported the use of a combination of a Ru complex (2 mol %) bearing two bidentate ( P , N H 2 ) ligands, KO t Bu (20 mol %) and Zn salts (4 mol %), which promoted the hydrogenation of N -methyl amides at 100 °C, but the reactivity of sterically more demanding amides and primary amides was scant to moderate; the catalysis does not seem to be sustainable at elevated temperatures.…”

Ruthenium‐Pincer‐Catalyzed Hydrogenation of Lactams to Amino Alcohols

“…Recently,anumber of catalytic systems have demonstrated that ruthenium pincerc omplexes could function as advantageous catalysts in the directh ydrogenation of linear amides for the synthesis of the corresponding amines and primary alcohols. [10][11][12][13] Under mild reaction conditions, ruthenium pincer complex 1 (Ru-MACHO, Scheme 1), ac ommercially available bifunctional catalyst, has exhibited extremelyh igh catalytic activity in the hydrogenation of ketones, amides, and carboxyl esters in the presenceo fasuitable strong base. [14] In contrast, hydride analogue 2 (Ru-MACHO-BH,S cheme 1b) does not require as trong base for activation in similarh ydrogenation reactions,d ue to lack of ac hloride ligand.…”

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides

“…[1] Among them, reduction of carboxamides, commonly mediated by metal hydrides,i so ne of the most frequently used processes that potentially delivers three possible products:a ldehydes,a lcohols,a nd amines (Scheme 1A). In contrast, alcohols or amines could be formed when I fragments through either CÀNo rC ÀOb ond scission, respectively,a nd the resulting aldehydes or imine/iminium intermediates are reduced by the second hydride.Atpresent, the state-of-the-art approaches for reduction of amides to alcohols are catalytic hydrogenation by well-defined pincer complexes,b ased on Ru, Fe,a nd Mn, under ah ighly pressurized H 2 atmosphere, [4] whereas those for the production of amines are facilitated by either hydrosilylation [5] with various metals [6] or organoboranes [7] as catalysts or electrophilic activation of amides with triflic anhydride. In contrast, alcohols or amines could be formed when I fragments through either CÀNo rC ÀOb ond scission, respectively,a nd the resulting aldehydes or imine/iminium intermediates are reduced by the second hydride.Atpresent, the state-of-the-art approaches for reduction of amides to alcohols are catalytic hydrogenation by well-defined pincer complexes,b ased on Ru, Fe,a nd Mn, under ah ighly pressurized H 2 atmosphere, [4] whereas those for the production of amines are facilitated by either hydrosilylation [5] with various metals [6] or organoboranes [7] as catalysts or electrophilic activation of amides with triflic anhydride.…”