Direct Amide Synthesis from Either Alcohols or Aldehydes with Amines: Activity of Ru(II) Hydride and Ru(0) Complexes

Abstract

An in situ generated catalyst from readily available RuH(2)(PPh(3))(4), an N-heterocyclic carbene (NHC) precursor, NaH, and acetonitrile was developed. The catalyst showed high activity for the amide synthesis directly from either alcohols or aldehydes with amines. When a mixture of an alcohol and an aldehyde was reacted with an amine, both of the corresponding amides were obtained with good yields. Homogeneous Ru(0) complexes such as (eta(4)-1,5-cyclooctadiene)(eta(6)-1,3,5-cyclooctatriene)ruthenium [Ru(cod)(cot)] and Ru(3)(CO)(12) were also active in the amidation of an alcohol or an aldehyde with the help of an in situ generated NHC ligand.

Ruthenium-Catalyzed Amide-Bond Formation

“…In general, the reactions showed to be strongly sensitive to the steric hindrance of the substrates. Thus, branched primary alcohols and amines, such as 2,2-dimethylpropanol, 2-methylbutanol or 2-heptanamine, gave rise to lower conversions than the linear ones [101,115,116,119,124,125,129]. In the same line, cyclic secondary amines (e.g.…”

“…Ruthenium complexes, and especially NHC-compounds, have been the most widely studied [94], albeit highly efficient processes promoted by rhodium or silver have also been described [112,113]. In regard to ruthenium, both in-situ-generated catalytic systems (Table 1) [114][115][116][117][118][119][120][121][122][123] as well as well-defined catalysts 38-44 ( Figure 10) [124][125][126][127][128][129][130][131] have been reported. In most of the cases, high metal loadings (usually 5 mol%) and an excess of a strong base (10-40 mol% of NaH or KO-t-Bu) were required to achieve satisfactory yields in the amides.…”

“…On this basis, the same authors subsequently developed an effective protocol for synthesizing amides from aldehydes using [RuH 2 (PPh 3 ) 4 ] [119]. In combination with the imidazolium salt 35b (see Table 1), sodium hydride and acetonitrile, this complex readily converted a variety of aliphatic and aromatic aldehydes into amides (Scheme 30).…”

6.11 N-Acylation Reactions of Amines

“…Phosphinefree 399 NHC ruthenium-based catalytic systems have also been shown to display good activity for these types of oxidative amidation processes. 400 Other heterogeneous metal-based systems for the amidation of amines using alcohol donors include heterogeneous alumina-supported silver clusters, 401 and gold, gold/iron, nickel, or cobalt nanoparticles. 402 Related rutheniumbased catalytic systems have also been developed that employ alcohols for the N-acylation of azides as masked amine donors.…”

Amino-alcohol cyclization: selective synthesis of lactams and cyclic amines from amino-alcohols

“…10 Later, Murahashi showed the cyclization of 1,4-and 1, 5-amino-alcohols to cyclic amides by applying a hydrogen acceptor. [14][15][16][17] Results and discussion As Ru 3 (CO) 12 /CataCXium W PCy was shown to be a very effective catalytic system for alcohol amination, 6 we decided to use this system for the cyclization of amino-alcohols (Scheme 3). 11 Van Koten's group performed reactions of diols with aniline employing Ru-pincer complexes.…”