Selective Iron-Catalyzed Deaminative Hydrogenation of Amides

Abstract

The five-coordinate iron(II) hydride complex ( iPr PNP)Fe(H)CO ( iPr PNP = N[CH 2 CH 2 (P i Pr 2 )] 2 ) was found to selectively catalyze deaminative hydrogenation of amides to the corresponding amines and primary alcohols. It is one of the most active amide hydrogenation catalysts reported to date, with turnover numbers (TONs) in excess of 1000 observed for multiple substrates and TONs greater than 4000 obtained for activated formanilides. The amide C−N cleavage reactions occur with a preference for electron-withdrawing substituents and with greater activity for formamides compared with acetamides and benzamides. Stoichiometric reactions between ( iPr PNP)Fe(H)CO and formanilide afforded the new iron(II) complex ( iPr PN H P)Fe(H)CO(N(Ph)HCO) resulting from N−H addition across the Fe−N bond. Complexes of this type were identified as the resting state during catalytic hydrogenation reactions containing secondary amides. Addition of a Lewis acid cocatalyst provided further enhancement of the productivity of catalytic amide hydrogenations.

Manganese Complexes for (De)Hydrogenation Catalysis: A Comparison to Cobalt and Iron Catalysts

“…[71] Except for precatalyst Fe-2 a,i ntroduced by the group of Milstein, which can hydrogenate activated trifluoroacetamides, [72] all reports of iron-catalyzed amide hydrogenations are based on the Fe complex Fe-25 b [73,74] or its cyclohexyl derivative Fe-25 c. [75] Bernskoetter and co-workers achieved, to date,the lowest reported catalyst loadings for amide reduction (0.07 mol %, formamides) using Fe-4. [76] 2.6. Hydrogenation of CO 2…”

Rational selection of co-catalysts for the deaminative hydrogenation of amides

“…[1][2][3] However, the reduction of electron rich carboxylic acid derivatives, such as amides, is still difficult. 4,5 The ubiquity of the amide functional group in biological systems, pharmaceuticals, and industrial chemicals 6 has spurred considerable effort to create efficient catalytic systems for amide hydrogenation. Nevertheless, amides are still typically reduced using waste generating stoichiometric reagents, such as LiAlH 4 , and to date only a small number of homogenous catalysts can directly hydrogenate amides to amines.…”

From Ruthenium to Iron and Manganese—A Mechanistic View on Challenges and Design Principles of Base‐Metal Hydrogenation Catalysts

“…In the case of iron, the utilization of aminophosphines allowed the preparation of stable octahedral complexes such as cis ‐[(H 2 N‐CH(Ph)‐CH(Ph)‐PPh 2 ) 2 FeBr(CO)](BPh 4 ) . However, this complex was reported to be catalytically inactive in the transfer hydrogenation of ketones and no activity was reported for structurally related iron complexes .…”