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A low viscosity ionic liquid [bmim]NTf 2 was successfully used as a reaction medium in Pd-catalyzed Mizoroki-Heck, Suzuki-Miyaura and Stille coupling reactions. The yields are good to high, and comparable to those reported previously for high viscosity ionic liquids, such as [bmim]PF 6 and [bmim]BF 4 . The products are readily separated and a reaction medium containing the Pd-carbene catalyst was successfully recycled.

The radical carbonylation of 1,5-enynes la and 1b using TTMSS as radical mediator gave the predicted carbonylative cyclization products 2a and 2b, respectively, in poor yields. The isolation and characterization of reaction byproducts by X-ray crystallographic analysis suggest that the poor chain propagation can be attributed to the formation of long-lived 3-silyl-1-siloxyallyl radicals, produced by the addition of a (TMS) 3 Si radical onto the O-C double bond of the initially formed cyclopentanones.

The Mizoroki-Heck reaction was carried out using a fluorous ether F-626 as the solvent and a fluorous Pd carbene complex as the catalyst. When carboxylic acids are the products, separation of both the F-626 and the Pd catalyst from the products can be conveniently carried out by simple filtration. The F-626 filtrates containing the Pd catalyst can be recycled.

4-[(Trimethylstannyl)diphenylsilyl]butanoyl radical, arising from the corresponding 3-(stannylsilyl)propyl radical and CO, undergoes an SHi reaction at Si with extrusion of trimethyltin radical to give silacyclopentanone. The parent 3-(stannylsilyl)propyl radical was also found to isomerize to (3-stannylpropyl)silyl radical via a 1,4-Sn shift from Si to C with a rate constant of 9.3 x 10(4) s-1 at 80 degrees C. Ab initio and DFT MO calculations support a front-side attack mechanism.

Free-radical mediated stannylcarbonylation of azaenynes provides a general [n + 1]-type annulation approach leading to alpha-stannylmethylene lactams. The cyclization is unusual in its breadth, covering 4-exo, 5-exo, 6-exo, 7-exo, and 8-exo modes.

Diastereoselective [2 + 2] photocycloaddition of chiral cyclohexenone 1 with cyclopentene was conducted using a continuous microflow reactor. This reaction led to photoadducts 2 and 3 in a shorter ...

Figure 1. Concept of ketenyl radical trapping Radical carbonylation reactions are becoming a powerful tool for the introduction of carbon monoxide into organic molecules. We have previously reported that free-radical mediated stannylcarbonylation of alkynes provides a useful entry to α,βunsaturated acyl radicals, which are likely to exist in an equilibrium with α-ketenyl radicals. Intraand intermolecular trapping attempts of α,β-unsaturated acyl radicals/α-ketenyl radicals led us to postulate that ketenyl carbonyl has an electrophilic nature sufficient enough to allow for the attack of nitrogen nucleophiles, such as imines, oxazolines, and amines. While stannylcarbonylation of amino-substituted alkynes gave lactams, we were curious at knowing if the stannylcarbonylation of hydroxy-substituted alkynes would give the corresponding lactones or not, since nucleophilicity of alcohols is not so strong as that of amines. We report herein the results of the free-radical mediated stannylcarbonylation reaction of 5-hydroxyalkynes, which gave cyclized carbonylated products, lactols, as principal carbonylated products. Interestingly recent work of Nishii, Tanabe, and coworkers reported that lactols can be formed by radical carbonylation of cyclopropyl radicals, through the trapping of intermediary acyl radicals by an internal hydroxyl group. Choosing 4-pentyn-1-ol (1a), as a model compound, we examined AIBN-initiated stannylcarbonylation reaction. As shown in Scheme 1, the reaction gave cyclized carbonylated products, unsaturated lactone 3a and lactol 4a, whereas lactone 2a was formed in only a trace amount. The formation of lactol 4a presumably requires two equivalents of tributyltin hydride. In consistent with this, the reaction using 1.3 equiv of tributyltin hydride caused the shortage of tin hydride resulting in the recovery of 1a. With 3.1 equivalents of tin hydride, the yield of 4a increased up to 46%. We also examined stannylcarbonylation of 3-butyn-1-ol (1b) and 5-hexyn-1-ol (1c). These results are shown in Scheme 2.

The ruthenium-catalyzed carbonylation at the C−H bond of five-membered N-heteroaromatic compounds is described. The reaction of imidazoles with CO and olefins in toluene in the presence of a catalytic amount of Ru3(CO)12 results in carbonylation of the C−H bond at the 4-position (adjacent to the sp2-nitrogen) of the imidazole ring to give acylated imidazoles in good to high yields. A wide range of olefins can be utilized in the carbonylation reaction, and a variety of functional groups are compatible under the reaction conditions. Other five-membered N-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can also be used for the carbonylation reaction, and in all cases, carbonylation takes place exclusively at a C−H bond α to the sp2 nitrogen. The reactivity of the five-membered heterocycles corresponds to the pKa of the conjugate acid of these heterocycles. The higher the pKa of the substrate, the higher is the reactivity. This indicates that the pKa values are related to the ability of ...

The ruthenium-catalyzed carbonylation at the C-H bond of five-membered N-heteroaromatic compounds is described. The reaction of imidazoles with CO and olefins in toluene in the presence of a catalytic amount of Ru(3)(CO)(12) results in carbonylation of the C-H bond at the 4-position (adjacent to the sp(2)-nitrogen) of the imidazole ring to give acylated imidazoles in good to high yields. A wide range of olefins can be utilized in the carbonylation reaction, and a variety of functional groups are compatible under the reaction conditions. Other five-membered N-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can also be used for the carbonylation reaction, and in all cases, carbonylation takes place exclusively at a C-H bond alpha to the sp(2) nitrogen. The reactivity of the five-membered heterocycles corresponds to the pK(a) of the conjugate acid of these heterocycles. The higher the pK(a) of the substrate, the higher is the reactivity. This indicates that the pK(a) values are related to the ability of the nitrogen atom in the substrates to coordinate to a ruthenium center. The coordination of the substrates to the ruthenium center in the catalyst complex is a necessary prerequisite for the carbonylation to proceed.

The ruthenium-catalyzed carbonylation at a C-H bond in the benzene ring of a 2-phenyloxazoline is described. The reaction of 2-phenyloxazolines with CO and ethylene in toluene in the presence of a catalytic amount of Ru(3)(CO)(12) resulted in propionylation at an ortho C-H bond in the benzene ring. The presence of the oxazoline ring on the benzene ring is essential for the carbonylation to proceed. Other heterocycles, such as oxazine, oxazole, and thiazoline rings, also served as acceptable directing groups as did the oxazoline ring. A wide functional group compatibility was observed. The site selectivity of the carbonylation was examined using meta-substituted phenyloxazolines. It was found that the carbonylation took place exclusively at the less-hindered C-H bond, irrespective of the nature of substituents, indicating that the site selectivity was determined by steric factors. The reaction was also applicable, not only to a benzene ring, but also to naphthyl and thiophenyl rings. Olefins such as propene and trimethylvinylsilane in place of ethylene could also be used in the carbonylation reaction, while other olefins, such as 1-hexene, tert-butylethylene, vinylcyclohexane, isoprene, 1,5-hexadiene, cyclohexene, 1, 5-cyclooctadiene, styrene, methyl acrylate, vinyl acetate, allyltrimethylsilane, and triethoxyvinylsilane did not afford the coupling products. An equilibrium between 2-phenyloxazolines, carbon monoxide, and olefins exists on one hand and the corresponding ketones on the other hand, and product composition is governed by the equilibrium thermodynamics of the system. The results of deuterium labeling experiments suggest that the catalysis involves a reversible C-H bond cleavage and that the rate-determining step is not the cleavage of a C-H bond. The results of kinetic study of the effects of CO pressure show that the reaction rate accelerates with decreasing CO pressure.

An efficient cross-addition reaction of dienes with aldehydes was developed by using RuHCl(CO)(PPh3)3 as a catalyst to give a wide variety of beta,gamma-unsaturated ketones, where a pi-allylruthenium species, derived from hydroruthenation of diene, may be involved as a key intermediate.

Microreactors have brought significant improvements to chemical synthesis and production because of their advantageous characteristics over batch reactors, which include highly efficient mixing, efficient heat and mass transfer ability, precise control of the residence time, large surface area-to-volume ratio and high operational safety. Microreactor technology has been found to be beneficial for gas–liquid biphasic reactions, for which the large interfacial area between the two phases is ensured. Carbonylation reactions with carbon monoxide, by which a wide range of carbonyl compounds can be prepared, deal with a variety of reactive species, such as organo transition metals, radicals, cations and anions. These reactions have long been carried out using a glass batch flask or a stainless-steel made autoclave, however, carbonylation reactions using a flow microreactor are now rapidly increasing in popularity. This review focuses on a new greener wave of carbonylation reactions using a flow microreactor.

Free-radical carbonylation of omega-alkynylamines with tributyltin hydride gives a mixture of alpha-methylene lactams and alpha-stannylmethylene lactams. Nucleophilic addition of an internal amino group to the carbonyl group of alpha-ketenyl radicals is proposed as the cyclization step. The subsequent unusual 1,4-H shift from the resulting 1-hydroxyallyl radical, followed by elimination of the beta-tributyltin radical leads to the formation of alpha-methylene lactams.

The α-alkylation reaction of acetamides with primary alcohols to afford the corresponding amides was accomplished effectively using RuHCl(CO)(PPh3)3 as a catalyst, nitrogen tridentate ligand L1 as an additive, and KOtBu as a base. While the addition of bpy was effective only for benzylic alcohols, L1 affected the alkylation reaction when both benzylic and non-benzylic type alcohols were used.

The catalytic decarbonylation reaction of aliphatic carboxylic acids can be carried out in the presence of an iron complex, and it proceeds smoothly to give α-olefins with high selectivity.

Tin hydride mediated radical carbonylation and cyclization reaction was investigated using a variety of ω-alkynyl amines as substrates. In this reaction α-methylene and α-stannylmethylene lactams having five to eight membered rings were obtained as principal products. In cases where the nitrogen has a substituent capable of giving stable radicals, such as an α-phenethyl group, the lactam ring formation again took place with extrusion of an α-phenethyl radical. Coupled with the subsequent protodestannylation procedure (TMSCl plus MeOH), these reactions provide a useful entry to α-methylene lactams with incorporation of CO as a lactam carbonyl group. In cases where the amines do not have a substituent acting as a radical leaving group, a reaction course involving a 1,4-H shift is chosen so as to liberate tin radicals ultimately. Thus the proposed mechanism involves (i) nucleophilic attack of amine nitrogen onto a carbonyl group of α,β-unsaturated acyl radicals/α-ketenyl radicals via lone pair-π* interaction, which leads to zwitterionic radical species, (ii) the subsequent proton shift from N to O to give hydroxyallyl radicals, (iii) 1,4-hydrogen shift from O to C, and (iv) β-scission to give lactams with liberation of tin radicals. DFT calculations reveal that the 1,4-hydrogen shifts, the key step of the reaction mechanism, can proceed under usual reaction conditions. On the other hand, an S(H)i type reaction to give lactams may be the result of the β-scission of the similar zwitterionic radical intermediates. DFT calculations also predict that an S(H)i type reaction would result when the intermediate has a good (radical) leaving group such as a phenethyl group.

A novel [5+1] type carbonylative cycloaddition reaction has been developed using a Rh complex as catalyst. This reaction can convert readily available 3-acyloxy-1,4-enynes and CO to a wide range of functionalized resorcinols in good yields. A mechanism involving Rh-catalyzed cyclocarbonylation of 3-acyloxy-1,4-enynes accompanied by a 1,2-acyloxy shift is proposed for the present [5+1] type cycloaddition reaction.

Heteroarylsilanes can be synthesized by the reaction of heteroaromatic compounds with triorganovinylsilanes with the aid of a Ru3(CO)12-catalyst. A variety of heteroaromatic compounds can be used in this C–H/SiR3 coupling. The coupling reaction was observed to take place at a position β to the directing carbonyl group, e.g., ketone, ester, and amide, in the case of heteroaromatic compounds.

Lactonization of dialdehydes and keto aldehydes was effectively catalyzed by RuHCl(CO)(PPh(3))(3). A cascade lactonization sequence accompanied by cross-coupling with enones was also attained.