Ruthenium-catalyzed carbonylations

The typical operating conditions used by Braca et al in their study were 150 atm and 200°C (see Table VI). Because of the efficiency of the WGS reaction, reactions starting with charged H20 and CH3OH were often characterized by production of high levels of dimethyl ether, C02, and H2 according to the following equations (71)  

For mechanistic studies, then, it was necessary to minimize the effects of the WGS reaction (70, 72). As a result, the reaction conditions were essentially anhydrous, using dimethyl ether as substrate. Even so, complications of homologation reactions to ethyl-containing species were still significant. 

Carbonylation and Homologation of Dimethyl Ether and Homologation of Methanol and Methyl 

Reagents MeOH Me20 Me20 Me20 AcOMe Me20 Me20 

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Ruthenium-catalyzed carbonylations of a variety of heterocycles have been disclosed. With benzimidazole derivatives, the regioselectivity changes upon introduction of a C(2) substituent (Equations (107) and (108)).100... 

Allyl methylcarbonate reacts with norbornene following a ruthenium-catalyzed carbonylative cyclization under carbon monoxide pressure to give cyclopentenone derivatives 12 (Scheme 4).32 Catalyst loading, amine and CO pressure have been optimized to give the cyclopentenone compound in 80% yield and a total control of the stereoselectivity (exo 100%). Aromatic or bidentate amines inhibit the reaction certainly by a too strong interaction with ruthenium. A plausible mechanism is proposed. Stereoselective CM-carboruthenation of norbornene with allyl-ruthenium complex 13 followed by carbon monoxide insertion generates an acylruthenium intermediate 15. Intramolecular carboruthenation and /3-hydride elimination of 16 afford the -olefin 17. Isomerization of the double bond under experimental conditions allows formation of the cyclopentenone derivative 12. 

An allenylaldehyde can be transformed efficiently into an a-methylene-y-butyro-lactone by a ruthenium-catalyzed carbonylative cycloaddition process (Scheme 16.34) [37]. The reaction mechanism may involve a metallacyclopentene, which undergoes insertion of CO and reductive elimination leading to the product. 

Lee s group has also reported ruthenium-catalyzed carbonylative cyclization of 1,6-diynes. The noteworthy aspect of this cyclization is the unprecedented anti nucleophile attack on a 7i-alkyne complex bearing a ruthenium vinylidene functionality. A catalytic system based on [Ru(p-cymene)Cl2]2/P(4-F-C6H4)3/DMAP was active for the cyclization of 1,6-diyne 103 and benzoic acid in dioxane at 65 °Cto afford cydohexenylidene enol ester 104a in 74% yield after 24h [34]. Additional examples are shown in Scheme 6.35. 

Comparable lactones 19 can be synthesized from allenyl alcohols 18 by a ruthenium-catalyzed carbonylative cyclization [19] and an extension of this procedure to the synthesis of lactames 21 has also been reported [20]. 

Ruthenium complexes are also suitable catalysts for carbonylation reactions of a variety of substrates. Indeed, when a reaction leads to C-Ru or het-eroatom-Ru bond formation in the presence of carbon monoxide, CO insertion can take place at the coordinatively unsaturated ruthenium center, leading to linear ketones or lactones. Thus, ruthenium-catalyzed carbonylative cyclization was involved in the synthesis of cyclopentenones by reaction of allylic carbonates with alkenes in the presence of carbon monoxide [124] (Eq. 93). 

Abstract Ruthenium-catalyzed carbonylation reactions are described. The purpose of this chapter is to show how ruthenium complexes as catalysts are important in the recent development of carbonylation reactions. This review does not present a complete, historical coverage of ruthenium-catalyzed carbonylation reactions,but presents the most significant developments of the last 10 years. The emphasis is on novel and synthetic transformations of genuine value to organic chemists. Especially, this review will focus on carbonylative cycloadditions and carbonylation of C-H bonds. The review is generally organized according to the nature of the reaction. 

Scheme 7. Suggested mechanism for the ruthenium-catalyzed carbonylations of alcohols.

Ruthenium-catalyzed carbonylations of allylic compounds [62] were described in Chapter 11. Here, ruthenium-catalyzed carbonylative cyclization of allylic carbonates with alkenes, not alkynes, which offers a new route to cyclopentenones is revealed [63]. Treatment of allyl methyl carbonate with 2-norbornene in the presence of 2.5 mol% [RuCl2(CO)3]2 and 10 mol% Et3N in THE at 120°C for 5 h under 3 atm of carbon monoxide gave the corresponding cyclopentenone, exo-4-methyltri-cyclo[5.2.1.0 ]dec-4-en-3-one, in 80% yield with high stereoselectivity exo 100%) (Eq. 5.37). 

Scheme 1.3 (a-c) Ruthenium-catalyzed carbonylative synthesis of pyrones. 

Scheme 1.5 Ruthenium-catalyzed carbonylative reaction of cyclopropyl imines.

In addition to palladium catalysts, ruthenium catalysts were applied in carbonylative C-H activation reactions as well. Moore and colleagues described the first ruthenium-catalyzed carbonylative C-H activation reaction in 1992 [52], Orf/io-acylation of pyridine and other nitrogen-containing aromatic compounds can be carried out with olefins and CO, using Ru3(CO)i2 as the catalyst (Scheme 6.16). Interestingly, internal olefins, such as cis- and frawi-2-hexene, yield the same linear/branched product ratio as terminal olefins. 

In addition to the above-mentioned reactions, Murai s group developed several other ruthenium-catalyzed carbonylations of arenes with similar reaction conditions (Scheme 6.19). Here, aza-heterocycle [58], 2-phenyloxazolines [59], iV-py-ridylindolines [60], A -arylpyrazoles [61, 62], and 2-phenylpyridines [63], were carbonylated into the corresponding products with Ru3(CO)i2 or Ru/C as the catalyst. Besides these novel carbonylation reactions, ruthenium-catalyzed de-carbonylative cleavage of alkyl phenyl ketones producing phenyl derivatives were also discovered by this group [64]. 

More recently, Chatani and his researchers developed the ruthenium-catalyzed carbonylation at the ortho-C-H bonds of aromatic amides [65] to give phthali-mides as their products. Analogously, this reaction can also be transferred to even inactivated C(sp )-H bonds and yield the corresponding succinimides. (Scheme 6.20) [66] In both cases, the presence of 2-pyridinylmethylamino moiety is necessary for these transformations, because it plays an important role as a N,N-bidentate ligand to form a dinuclear ruthenium complex with Ru3(CO)i2. Interestingly, in the absence of ethylene, no carbonylation product could be detected while the efficiency of the reaction decreased in the absence of water. In the latter case, a long reaction time (5 days) is still needed. 

Zbieg JR, Mclnturff EL, Krische MI (2010) Allenamide hydro-hydroxyalkylation 1,2-aminoalcohols via ruthenium-catalyzed carbonyl ann -aminoallylation. Org Lett 12 2514—2516... 

Liang T, Nguyen KD, Zhang W, Krische MI (2015) Enantioselective ruthenium-catalyzed carbonyl allylation via alkyne-alcohol C-C bond forming transfer hydrogenation aUene hydrometallation vs. oxidative coupling. J Am Chem Soc 137 3161-3164... 

A ruthenium-catalyzed carbonylative coupling of furfural imine 41 and ethylene was described by Murai and co-workers (Schane 10.13)." The imine directing group was found to be necessary to attain high efficiency and regioselectivity for cleavage of the C—H bond ortho to the imine." Product formation probably occurs via metallation of the furfural imine (I), reaction with ethylene and CO insertion... 

Pyridine itself can be reacted with olefins and carbon monoxide in the presence of a catalytic amount of Ru3(CO)i2 to give a-acylated pyridines (eq 8)T A number of olefins react with the pyridine to afford the corresponding linear p)ridyl ketones as the major products. The ruthenium-catalyzed carbonylation of 1,2-disubstituted imidazoles with olefins and carbon monoxide provides C-C bond formation at the 4-position (eq Various functional groups, e.g., ether, acetal, ester, imide, and nitrile are tolerant to the reaction conditions. The reaction of 1-methylpyrazole under similar carbonylation conditions gives 3-pyrazolyl ketones (eq 10). This result is in contrast to the Friedel-Crafts acylation of a pyrazole ring, which yields 4-pyrazolyl ketones. ... 

This monograph is not intended to provide a comprehensive view of all ruthenium-catalyzed reactions, as this metal and its numerous complexes are now involved in many useful catal3 tic transformations. For instance, ruthenium-catalyzed carbonylation, polymerization, enantioselective hydrogenation and cyclopropanation... have not been included in spite of their high interest in synthesis. 

Development of new methods for the synthesis of cyclic amide compounds is important in view of medicinal chemistry. Scheme 11.12 indicates an example of ruthenium-catalyzed carbonylation of allenylamines with CO [15]. 

Scheme 7.14 Proposed mechanism for ruthenium-catalyzed carbonylation and cyclization of aliphatic amides.

Ruthenium-catalyzed carbonylative [5+1] cyclo-addition of cyclopropyl imines and CO Summary References... 

Ruthenium-Catalyzed Carbonylative [5+1] Cycloaddition of Cyclopropyl Imines and CO... 

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