MoS2-Catalyzed transamidation reaction

The MoS2-catalyzed transamidation reaction with high yields using N,N-dimethylformamide and other amides as carbonyl sources is developed here. The protocol is simple, does not require any additive such as acid, base, ligand, etc., and encompasses a broad substrate scope for primary, secondary and heterocyclic amines. Moreover, the acetylation and propanylation of amines also can be achieved with good to excellent yield by this strategy.

www.nature.com/scientificreports www.nature.com/scientificreports/ compound 2o which containing trifluoromethyl group, a marker for fluoxetine 51 , could be synthesized by this strategy with good yield (78%). However, the substrate with obvious steric hindrance group, such as ethyl (1j) on nitrogen was suffered from a reduced yield. This transamidation strategy was also applicable to primary amines, and good results as well as secondary amines were achieved (2p-v). Particularly, substrate containing hydroxyl group also converted to desired product with good yield (2 u). The transamidation reaction and the corresponding product are valuable in organic synthesis reaction. For example, the natural product homoveratrylamine (1x) can be modified with formyl group by this strategy, and the corresponding product 2x could be converted to a series of natural compounds such as pseudopalmatine, 8-oxopseudopalmatine, and ilicifoline B 52 . However, when aromatic amines such as aniline, tetrahydroquinoline and tetrahydroindole were used as substrates, only trace amount of desired products could be detected.
After the expanded substrate scope of amines, we then considered other appropriate carbonyl sources except DMF (Fig. 5). The results showed this reaction could also be proceeded with excellent yield by using formamide or N-methylformamide as formyl sources (entries 1-2). However, in the case of using sterically hindered amide such as N,N-diethylformamide as substrate, the yield would be reduced seriously (entry 3). Delightedly, acetamide and propionamide could be applied as carbonyl sources, and the corresponding N-acetylation and N-propionylation reaction were achieved with excellent yields (entries 4-5). These results further confirmed the transamidation strategy developed by us has a broad scope and is valuable. Moreover, in the case of aromatic amides used as carbonyl sources, a yield of 30~40% still could be found (entries 6-7). www.nature.com/scientificreports www.nature.com/scientificreports/ To verification the practicability of this strategy, the N-acetylation and N-propionylation reaction were expanded (Fig. 6). Either primary amines or secondary amines were converted to corresponding products with good to excellent yields (2zc-zl).
Significantly, the gram-scale synthesis of 2g using only 3 mol% MoS 2 as catalyst was proceeded (Fig. 7A), and an excellent yield of 93% was obtained with an extended reaction time (4 days). Subsequently, the radical blocking experiments were performed using 1 equiv butylated hydroxytoluene (BHT), quinone, or 1,1-diphenylethene as a blocker, and the transamidation products were achieved with 80%, 83%, and 82% yield, respectively (Fig. 7B). These results indicated that this process is not a radical reaction, but a nucleophilic reaction.
Based on the radical blocking experiments and previous reported metal-catalyzed transamidation reactions [13][14][15] , the reaction mechanism was proposed (Fig. 8). First, MoS 2 coordinated with DMF, and the carbonyl group is activated. Then, substrate amine acting as a nucleophilic reagent attacks the carbonyl group of the acti-

Conclusions
In summary, an efficient MoS 2 -catalyzed transamidation reaction using amides as carbonyl sources was reported. The advantages of this reaction are the readily available and inexpensive metal applied as catalyst, cheap amides applied as carbonyl source, scalable, broad scopes, free of any additives such as acid, base, ligand, and etc.

Materials and Methods
General Information. The prepared thin-layer chromatography (Prep TLC) was performed for product purification using Sorbent Silica Gel 60 F254 TLC plates and visualized with ultraviolet light. IR spectra were recorded on a new Fourier transform infrared spectroscopy. 1 H, 13 C and 19 F NMR spectra were recorded on 400, 100, 377 MHz NMR spectrometer using CDCl 3 as solvent unless otherwise stated. HRMS were made by means of ESI. Melting points were measured on micro melting point apparatus and uncorrected. Unless otherwise noted, all reagents were weighed and handled in the air, and all reactions were carried out in a sealed tube under an atmosphere of argon. Unless otherwise noted, all reagents were purchased from reagent company, and used without further purifications. Notably, the powder MoS 2 were used in this work.   www.nature.com/scientificreports www.nature.com/scientificreports/ experimental section. A typical experimental procedure for transamidation was conducted as follows: A solution of amine (0.2 mmol), MoS 2 (12.5 mol%, 4 mg) in DMF (1.0 mL) was stirred in a sealed tube under an atmosphere of argon at 150 °C for 18 h. After being cooled to room temperature, the reaction mixture was filtered, washed with ethyl acetate (20 mL). Afterward, the solution was added 10 mL water and extracted with ethyl acetate (3 × 15 mL), and then the combined organic layers were dried with Na 2 SO 4 . The solvent was evaporated under vacuum and the crude product was purified by Prep TLC on silica gel with petroleum ether and ethyl acetate to obtain the pure product.