Ruthenium-Catalyzed Redox-Neutral and Single-Step Amide Synthesis from Alcohol and Nitrile with Complete Atom Economy

Abstract

A completely atom-economical and redox-neutral catalytic amide synthesis from an alcohol and a nitrile is realized. The amide C-N bond is efficiently formed between the nitrogen atom of nitrile and the α-carbon of alcohol, with the help of an N-heterocyclic carbene-based ruthenium catalyst, without a single byproduct. A utility of the reaction was demonstrated by synthesizing (13)C or (15)N isotope-labeled amides without involvement of any separate reduction and oxidation step.

2‐Furanylboronic Acid as an Effective Catalyst for the Direct Amidation of Carboxylic Acids at Room Temperature

“…The best solvents for catalyst 1g turned out to be similar to those reported for 1c, [8b] with CH 2 Cl 2 (entry 1) and toluene (entry 4) being the most suitable, and diethyl ether (entry 7) also performed well. [12] Having identified the best solvent, we next turned our attention to other reaction parameters, including the amount of 4 Å molecular sieves used, substrate concentration and catalyst loadings ( Table 2, entries [12][13][14][15][16][17][18][19]. [12] Having identified the best solvent, we next turned our attention to other reaction parameters, including the amount of 4 Å molecular sieves used, substrate concentration and catalyst loadings ( Table 2, entries [12][13][14][15][16][17][18][19].…”

“…Higher polarity solvents including tetrahydrofuran (THF), 2-Me-THF, acetonitrile, dioxane and ethanol gave much lower yields, whereas the use of N,N-dimethylformamide (DMF) led to transamidation, forming N-benzylformamide as a side-product. [12] Having identified the best solvent, we next turned our attention to other reaction parameters, including the amount of 4 Å molecular sieves used, substrate concentration and catalyst loadings ( Table 2, entries [12][13][14][15][16][17][18][19]. Optimal conditions were found to be 10 mol-% catalyst loading, 0.16 m carboxylic acid 2a in CH 2 Cl 2 and 1 g of 4 Å molecular sieves (MS) per millimole of amine 3a (entry 17).…”

“…The mixture was stirred vigorously for 10 min before amine (1.0 mmol, 1.0 equiv.) N-(4-Chlorobenzyl)-2-phenylacetamide (4ab): [18] Yield 251 mg (97 %); white solid. The resulting mixture was stirred at room temperature for 24 h. The reaction mixture was filtered through a pad of Celite, and the filtrate was washed with 0.1 m HCl solution, followed by saturated sodium carbonate solution and brine.…”

Ruthenium-Catalyzed Amide-Bond Formation

“…Worthy of note, this methodology offered an easy entry to 15 Nlabeled amides starting from 15 N-azides, which are readily accessible from alkyl halides and commercially available 15 N-labeled NaN 3 [134]. More recently, the same authors have extended their studies to the synthesis of amides from alcohols and nitriles, via formation of a transient hemiaminal intermediate (Scheme 27) [135]. Among the different catalysts tested, the best performances were reached with the dihydride-ruthenium derivative [RuH 2 (CO)(PPh 3 ) 3 ].…”

Atom-economic dehydrogenative amide synthesis via ruthenium catalysis

“…However, they usually require stoichiometric amounts of reagents and generate equimolar amounts of by-products as waste, which is not in accordance with the concept of "green and sustainable chemistry". [16][17][18][19][20][21] In this article, recent development of these methods and current challenges in this area are presented. 1).…”