Tungsten‐Catalyzed Direct N‐Alkylation of Anilines with Alcohols

Abstract

The implementation of non‐noble metals mediated chemistry is a major goal in homogeneous catalysis. Borrowing hydrogen/hydrogen autotransfer (BH/HA) reaction, as a straightforward and sustainable synthetic method, has attracted considerable attention in the development of non‐noble metal catalysts. Herein, we report a tungsten‐catalyzed N‐alkylation reaction of anilines with primary alcohols via BH/HA. This phosphine‐free W(phen)(CO)4 (phen=1,10‐phenthroline) system was demonstrated as a practical and easily accessible in‐situ catalysis for a broad range of amines and alcohols (up to 49 examples, including 16 previously undisclosed products). Notably, this tungsten system can tolerate numerous functional groups, especially the challenging substrates with sterically hindered substituents, or heteroatoms. Mechanistic insights based on experimental and computational studies are also provided.

Selective C‐alkylation Between Alcohols Catalyzed by N‐Heterocyclic Carbene Molybdenum

“…On one hand, Bullock, [19] Beller, [20] Berke, [21] Topf [22] and Waymouth [23] reported molybdenum complexes in catalyzed hydrogenation reactions and transfer hydrogenation reactions. On the other hand, recently N ‐alkylation of amine by alcohol catalyzed by Cr(III) and W(0) complexes have been disclosed by Kempe's group [24] and our group [25] , respectively. These results indicate the potential of VIB group metal catalysts, especially molybdenum, in BH/HA reactions.…”

N‐Alkylation of α‐Amino Esters and Amides through Hydrogen Borrowing

“…Subsequent imine formation and reduction by the hydrogen stored on the catalyst gives the alkylated amine in a one pot process. Ir [7] and Ru [8] complexes are well known to catalyse this transformation, and more recently Ni, [9] Cu, [10] Co, [11] Mn, [12] Fe, [13] W [14] and organocatalytic [15] systems have been developed.…”

Enhanced Hydride Donation Achieved Molybdenum Catalyzed Direct N-Alkylation of Anilines or Nitroarenes with Alcohols: From Computational Design to Experiment

“…The borrowing hydrogen or hydrogen autotransfer (BH/HA) methodology (Scheme a) using alcohols as alkylation reagents is a green and sustainable method to replace the traditional synthetic way, in which the hazardous alkyl halides are used as reactants while undesirable side products or wastes are unavoidable. Various catalytic systems for N -alkylation have been developed using this BH/HA methodology, including widely investigated noble-metal-based homogeneous catalysts, like Ir, Ru, Pd, etc., and recently emerging nonprecious metal homogeneous systems such as Fe, Co, Mn, , Ni, Cr, and W …”

“…The homogeneous Mo-catalyzed BH/HA N -alkylation of amines or nitroarenes with alcohols is yet to be realized. As part of our ongoing interest in BA/HA, ,, herein, we reported the first example of a non-noble Mo catalytic system for this transformation (Scheme c).…”

“…A possible outer-sphere mechanism for this catalyst system was proposed, ,, which includes precatalyst activation, alcohol dehydrogenation, imine in situ formation, and imine hydrogenation. First, one CO ligand would disassociate to form the active species Mo-1a with a vacant site.…”