Transamidation of Amides and Amidation of Esters by Selective N–C(O)/O–C(O) Cleavage Mediated by Air- and Moisture-Stable Half-Sandwich Nickel(II)–NHC Complexes

Abstract

The formation of amide bonds represents one of the most fundamental processes in organic synthesis. Transition-metal-catalyzed activation of acyclic twisted amides has emerged as an increasingly powerful platform in synthesis. Herein, we report the transamidation of N-activated twisted amides by selective N–C(O) cleavage mediated by air- and moisture-stable half-sandwich Ni(II)–NHC (NHC = N-heterocyclic carbenes) complexes. We demonstrate that the readily available cyclopentadienyl complex, [CpNi(IPr)Cl] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), promotes highly selective transamidation of the N–C(O) bond in twisted N-Boc amides with non-nucleophilic anilines. The reaction provides access to secondary anilides via the non-conventional amide bond-forming pathway. Furthermore, the amidation of activated phenolic and unactivated methyl esters mediated by [CpNi(IPr)Cl] is reported. This study sets the stage for the broad utilization of well-defined, air- and moisture-stable Ni(II)–NHC complexes in catalytic amide bond-forming protocols by unconventional C(acyl)–N and C(acyl)–O bond cleavage reactions.

Facile Synthesis of Amides through Transamidation with Iodine under Neat Conditions

“…[15][16][17][18][19][20][21][22][23] The utilization of metal catalysts to generate amides from various starting materials has a particular area of interest for the various research groups. Ni(II) metal complex, [24] Ni-(quin) 2 , [25] has recognized as a highly efficient catalyst for the Nformylation and N-acylation of aromatic, aliphatic, and heterocyclic amines. Gong and co-workers have also reported the transamidation reaction, using 15 mol% Cobalt (II) at 150 °C temperature.…”

[Ni(Np#)(η5-Cp)Cl]: Flexible, Sterically Bulky, Well-Defined, Highly Reactive Complex for Nickel-Catalyzed Cross-Coupling

“…Simultaneously, Ni–NHC complexes have recently garnered significant attention as homogeneous catalysts in organic synthesis owing to the advantages of Ni as an abundant and inexpensive 3d transition metal. − However, despite intensive research efforts, there are still few examples of well-defined and air-stable Ni­(II)–NHC precatalysts for cross-coupling reactions. , Out of several classes of well-defined Ni­(II)–NHCs available, − [Ni­(NHC)­(η 5 -Cp)­Cl] complexes supported by the cyclopentadienyl throw-away ligand are considered particularly attractive owing to the ease of synthesis, high air and moisture stability, and facile activation to Ni(0). − …”

“…The major challenge in developing new [Ni­(NHC)­(η 5 -Cp)­Cl] complexes includes less defined reactivity trends in NHC ligands coordinated to Ni, especially as compared with Pd–NHC catalysis − where IPr (IPr = 1,3-bis­(2,6-diisopropylphenyl)­imidazol-2-ylidene) is generally considered as the “first-choice” privileged ligand for catalysis . However, it is worth pointing out that some of the reactivity of IPr have been superseded by IPr* and IPent and derivatives, especially in the field of palladium catalysis. − , Further challenges in developing new Ni–NHC catalysts include the shorter lifetime of active catalyst species and high activation barrier to generate the active Ni catalyst. , Consequently, these challenges have created an attractive research frontier to access new well-defined Ni–NHCs for catalysis research. − …”

Environmentally Benign Transamidation Protocol for Weakly Nucleophilic Aromatic Amines with N‐Acyl‐2‐piperidinones: Catalyst‐, Additive‐, Base‐ and Solvent‐Free Condition

“…For example, N-activation by acylation/tosylation, [12,5] N-activation-metal catalyzation, [5,9,13,14] amide bond twist, [4,15] and amide bond twist-metal catalyzation. [15,16] Most of these developed methods deploy either catalyst that is metals such as Ni, [10,[17][18][19] Pd, [9,20,21] Ce, [22,23] Fe, [24] Cu, [25] W [6] and lanthanides [26] or activating agents to realize transamidation. In metal-catalyzed reactions, metals have to be carefully removed to obviate metal toxicity especially in pharmaceuticals.…”