Search

The synthesis of new functional organic molecules that cannot be obtained by a simple combination of conventional synthetic methods is a challenging subject in organic, organometallic, and industrial chemistry as well as in atom-efficient and environmental organic synthesis. Among the various possibilities that have been considered, the catalytic cleavage and reconstruction of the C–C bond has opened the door to a new branch of synthetic organic chemistry. This microreview summarizes progress on the ruthenium- and rhodium-catalyzed strain-driven cleavage of the C–C bond, the methods of which were mostly developed by the author. The direct oxidative addition of 2,5-norbornadienes, cyclopropenones, cyclobutenones, and cyclobutenediones, and to catalytically active metal species followed by the construction of the C–C bond has been used for the preparation of new organic molecules.

We report the application of one-dimensional triple-resonance NMR to metabolic analysis and thereon-based evaluation of drug activity. Doubly (13)C/(15)N-labeled uracil ([(15)N1,(13)C6]-uracil) was prepared. Its catabolic (degradative) conversion to [(13)C3,(15)N4]-β-alanine and inhibition thereof by gimeracil, a clinical co-drug used with the antitumor agent 5-fluorouracil, in mouse liver lysates were monitored specifically using one-dimensional triple-resonance ((1)H-{(13)C-(15)N}) NMR, but not double-resonance ((1)H-{(13)C}) NMR, in a ratiometric manner. The administration of labeled uracil to a mouse resulted in its non-selective distribution in various organs, with efficient catabolism to labeled β-alanine exclusively in the liver. The co-administration of gimeracil inhibited the catabolic conversion of uracil in the liver. In marked contrast to in vitro results, however, gimeracil had practically no effect on the level of uracil in the liver. The potentiality of triple-resonance NMR in the analysis of in vivo pharmaceutical activity of drugs targeting particular metabolic reactions is discussed.

A novel zerovalent ruthenium complex with a π-acidic ligand, Ru(η (6)-cyclooctatriene)(η (2)-dimethyl fumarate)2 (1), was prepared from Ru(η (4)-cyclooctadiene)(η (6)-cyclooctatriene) [Ru(cod)(cot)]. Complex 1 or Ru(cod)(cot) catalyzes various new carbon-carbon bond-forming reactions that include the [2 + 2] cycloaddition of alkenes and alkynes via ruthenacycles, the creation of a new hydrocarbon, pentacyclo[6.6.0.0(2,6).0(3,13).0(10,14)]tetradeca-4,11-diene [PCTD], by dimerization of 2,5-norbornadiene via C-C bond cleavage, and the codimerization of alkynes and/or alkenes. Complex 1 was shown to be an excellent mother complex for various zerovalent ruthenium complexes. Complex 1 reacts with amines, phosphines or water to give new zerovalent ruthenium complexes with the ligands. The resulting aqua complexes have a water ligand with an oxygen atom that is a chiral center, i.e., ruthenium complexes with a 'chiral water' ligand were prepared and fully characterized.

A neutral rhodium(I) complex, ‘RhCl(PPh 3 ) 2 ’ generated by the combination of [RhCl(C 2 H 4 ) 2 ] 2 with a fourfold amount of PPh 3 , effectively catalyzed the cyclocotrimerization of alkynes ( 1 ) and isocyanates ( 2 ) to give 2-pyridones ( 3 ) and/or pyrimidine-2,4-diones ( 4 ), selectively, by controlling the molar ratio of alkynes ( 1 ) and isocyanates ( 2 ).

Formal [4 + 2] cycloaddition of alkynes with electron-deficient alkenes, which affords 3,6-dialkyl-4-cyclohexene-1,2-dicarboxylates, was achieved using Ru(η 6 -1,3,5-cyclooctatriene)(η 2 -dimethyl fumarate) 2 as a catalyst. The reaction mechanism consists of two steps, isomerization of an alkyne to conjugated dienes and successive Diels–Alder reaction of the generated dienes with an electron-deficient alkene.

The novel title catalyst system enables a simple, selective, and practical synthesis of indoles from aminoalcohols.

Low-valent ruthenium complexes often show intriguing and characteristic catalytic activity for novel organic transformations with high atom efficiency. The design and synthesis of novel low-valent ...

Indole derivatives were readily prepared from the reductive N-heterocyclization of o-nitrostyrene derivatives in the presence of a catalytic amount of PdCl2(PPh3)2–SnCl2 under carbon monoxide pressure (20 kg/cm2) at 100 °C for 16 h. With o-nitrostilbene, 2-phenylindole was obtained in 75% yield.

Allylamines react with acrylic compounds in the presence of Ru(cod)(cot) catalyst to give cyclobutane-β-amino acid derivatives in high yield (up to 85%); cod = cycloocta-1,5-diene, cot = cycloocta-1,3,5-triene.

Ru(cod)(cot) catalyzes highly selective codimerization of 1,3-dienes with acrylic compounds and first linear coupling reaction of allylic carbonates with the acrylic amide to give 3,5-dienoic acid derivatives; cod = cycloocta-1,5-diene, cot = cycloocta-1,3,5-triene.

Allylic carbonates except for allyl methyl carbonate reacted with carbonucleophiles such as ethyl acetoacetate in the presence of a catalytic amount of Ru(cod)(cot) [cod = cycloocta-1,5-diene, cot = cycloocta-1,3,5-triene] in N -methylpiperidine at 80°C to give the corresponding monoallylated carbonucleophiles in high yields with high regioselectivity. The regioselectivity was quite different from that in the palladium-catalyzed reactions. The allylation of carbonucleophiles using allyl methyl carbonate selectively gave the diallylated carbonucleophiles in high yields.

Ruthenium complex-catalyzed N-heterocyclization of 2-aminopyridines with vicinal-diols offers a novel synthetic method for various imidazo[1,2-a]pyridines. For example, the reaction of 2-amino-4-methylpyridine with 1,2-cyclohexanediol in the presence of a catalytic amount of RuCl2(PPh3)3 under reflux in diglyme for 24 h afforded 2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]benzimidazole in 74% yield.

Co2(CO)8-catalyzed ring-opening carbonylation of oxiranes and oxetane smoothly proceeds with high regioselectivity under 1 atm of carbon monoxide at room temperature to give the corresponding β- and γ-siloxy amides in high yields, respectively. [(R3Si)2NR1R2]+[Co(CO)4]− is thought to be an active catalyst species and directs the high regioselectivity of the carbonylation.

The dichlorobis(triphenylphosphine)palladium (PdCl 2 (PPh 3 ) 1 )-tin(II) chloride (SnCl 2 ) system shows high catalytic activity for the reductive N-heterocyclization of various 2-nitrostyrene and N-(2-nitrobenzylidene)amine derivatives when employed at 100 o C for 16 h under 20 kg cm -2 of initial carbon monoxide pressure, to give the corresponding indole and 2H-indazole derivatives in good yield. For example, 2-phenylindole was obtained in 75% yield from the reductive N-heterocyclization of 2-nitrostilbene

Ru{sub 3}(CO){sub 12}/1,10-phenanthroline catalyzes the carbonylation of allylic alkyl carbonates to give esters. The authors studied this reaction with various substrates at different CO pressures.

A combination of the palladium complex PdCl2(PPh3)2 with MoCl5 shows a high catalytic activity for the intermolecular reductive N-heterocyclization of 2-nitrobenzaldehyde or 2-nitrophenyl ketones with formamide to give the corresponding quinazoline derivatives in moderate yields. For example, in the reaction of 2-nitrobenzaldehyde with formamide, quinazoline was obtained in 46% yield. We assume that the present reaction proceeds via an active nitrene intermediate which would be generated by selective deoxygenation of nitro group by carbon monoxide.

The following ruthenium-catalyzed novel transformations of alkyl formates have been developed: (1) selective decarbonylation of alkyl formates to the corresponding alcohols; (2) alkylation of arenes and alkenes using alkyl formates as an alkylating reagent via decarboxylation. Also the ruthenium-catalyzed addition of alcohols to alkenes has been developed as an appendant reaction, providing an effective method for the protection of alcohols.

Heteroaromatic amines were N-alkylated with primary alcohols at 150−200 °C in the presence of a catalytic amount of various ruthenium complexes to give the corresponding monoalkylated and dialkylated amines in good to high yields. For example, 2-aminopyridine reacted with an excess of ethanol at 180 °C for 20 h in the presence of dichlorotris(triphenylphosphine)ruthenium [RuCl2(PPh3)3] to give 2-(ethylamino)pyridine (1) and 2-(diethylamino)pyridine (2) in 9% and 70% yields, respectively. On the other hand, when (η4-1,5-cyclooctadiene)(η6-1,3,5-cyclooctatriene)ruthenium [Ru(cod)(cot)] was used as a catalyst, even in the presence of excess ethanol, 1 was obtained in 85% yield with high selectivity. The addition of tertiary phosphines and phosphites to Ru(cod)(cot) increased the yield of the dialkylated amine.

Various N,N‘-disubstituted and trisubstituted ureas were obtained in high yields by the ruthenium-complex-catalyzed dehydrogenation of N-substituted formamides and amines under reflux in mesitylene for 12 h under an argon atmosphere. From formanilide (1a) and aniline (2a), N,N ‘-diphenylurea (3a) was obtained in 92% yield. During this reaction, a stoichiometric amount of gaseous hydrogen was spontaneously evolved; thus, the addition of a hydrogen acceptor was not required. Formamide itself, i.e., HCONH2 (4), can also be used as a versatile carbonyl source. From HCONH2 (4) and primary amines, the corresponding N,N‘-disubstituted ureas were obtained in high yields together with the evolution of hydrogen and ammonia. To identify a catalytically active species, the stoichiometric reaction of RuCl2(PPh3)3 with formanilide (1a) was carried out in CH2Cl2 at room temperature to give a novel oxygen-atom-bridged dinuclear ruthenium complex, Ru2(μ-Cl)2Cl2(μ-PhNHCHO-O,O)(PPh3)4 (5), in 87% yield. Complex 5 showed a h...

Unsymmetrically substituted hydroquinones were obtained in high yields by the novel ruthenium-catalyzed cross-carbonylation of alkynes and 2-norbornenes. For example, treatment of 4-octyne and 2-norbornene with 2 mol % Ru3(CO)12 in N-methylpiperidine under 60 atm of carbon monoxide at 140 °C for 20 h gave the corresponding hydroquinone, 4,5-dipropyltricyclo[6.2.1.02,7]undeca-2(7),3,5-triene-3,6-diol, in 85% yield. The reaction apparently involves a maleoylruthenium intermediate which is generated by the reaction of an alkyne and two molecules of carbon monoxide on the ruthenium.

A novel ruthenium catalyst system of [PPN][Ru3H(CO)11]/PCy3 [PPN = bis(triphenylphosphine)iminium, Cy = cyclohexyl] for the direct hydroamidation and hydroesterification of alkenes with formamides and alkyl formates has been developed. These addition reactions proceeded smoothly under an argon atmosphere, and carbon monoxide is not needed to suppress decarbonylation of formyl compounds or to maintain the catalytic activity.

Low-valent ruthenium complexes with a p-acidic ligand, such as Ru(h 6 -cot)(dmfm)2 [cot 1,3,5-cyclooctatriene, dmfm dimethyl fumarate] and Ru3(CO)12, showed high catalytic activity for the intramolecular hydroamination of aminoalkynes. The reaction is highly regioselective, in which a nitrogen atom is selectively attached to an internal carbon of alkynes to give five-, six-, and seven-membered nitrogen heterocycles as well as indoles in good to high yields. © 2001 Elsevier Science B.V. All rights reserved.

The development of efficient methods for the selective formation and cleavage of C-C bonds leading to construction of new carbon skeletons catalyzed by transition-metal complexes is a central and challenging subject of modern organic synthesis. Among the various transition-metal complexes, we have recently focused our attention on novel catalytic activity of low valent ruthenium complexes, since ruthenium complexes often show interesting catalytic activity and product selectivity, which are quite different from those with palladium and other transition-metal complexes. Here, we report our recent results of novel catalytic performance of ruthenium complexes for organic synthesis, which include (1) ruthenium-catalyzed novel C-C bond formation using an ambiphilic reactivity of π-allylruthenium complexes as well as the selective cleavage of C-C bonds via β-allyl elimination, (2) ruthenium-catalyzed novel methods for preparation of cyclopentenones via ruthenacycle intermediates, and (3) ruthenium-catalyzed novel transformation of sulfur-containing compounds, which enables simple, selective and general syntheses of vicinal-dithioethers and allylic sulfides.

Novel alkenylene-bridged oligosilsesquioxanes composed of half-caged structures with 16- or 17-membered rings as well as a titanium-containing molecule with a twisted 21-membered macrocycle have been synthesized by ruthenium or rhodium-catalyzed ring-closing reactions of silsesquioxanes with bis(allyldimethylsilyl) groups.

[RuCl2(CO)3]2/dppp is shown to be a highly effective catalyst system for the first intramolecular oxidative amination of a variety of aminoalkenes when it is used concomitantly with K2CO3 and allyl acetate in N-methylpiperidine, to give the corresponding cyclic imines and indoles in excellent yields. For example, the reaction of 2,2-diphenyl-4-pentenyl-1-amine performed in the presence of 2 mol % of [RuCl2(CO)3]2, 4 mol % of dppp, K2CO3, and allyl acetate in N-methylpiperidine at 140 °C for 8 h gives 4,4-diphenyl-2-methyl-1-pyrroline in quantitative (>99%) yield.

Novel catalytic reactions via ruthena- or rhodacyclic intermediates developed by our research group are reviewed. We initiate our study from (1) ruthenium-catalyzed [2 + 2] cycloaddition of alkynes with alkenes, followed by developing (2) intramolecular Pauson-Khand-type reaction of 1, 6-enynes, (3) hydroquinone synthesis, (4) codimerization of styrenes with ethylene . Another approach to construct novel functional monomers, such as cyclopentenones, pyranopyrandiones, and phenols, involves cleavage of carbon-carbon bonds in cyclobutenediones, cyclopropenones, and cyclobutenones. All reactions proceed with high atom-efficiency via ruthena- or rhodacyclicintermediates. In addition, rhodium-catalyzed [2 + 2 + 2] cocyclization of alkynes with isocyanates as well as novel ruthenium-catalyzed [2 + 2 + 1] cocyclization of alkynes, isocyanates, and carbon monoxide have been disclosed.

Novel catalytic reactions via ruthena- or rhodacyclic intermediates have been developed by our research group. We initiated our study from (1) ruthenium-catalyzed [2+2] cycloaddition of alkynes with alkenes, followed by developing (2) intramolecular Pauson-Khand-type reaction of 1,6-enynes, (3) hydroquinone synthesis, (4) cyclocotrimerization reactions, and (5) codimerization of styrenes with ethylene. Another approach to construct novel functional monomers, such as cyclopentenones, pyranopyrandiones, and substituted phenols, involves cleavage of carbon-carbon bonds in cyclobutenediones, cyclopropenones, and cyclobutenones. All reactions may proceed with high atom-efficiency via ruthena- or rhodacyclic intermediates, represented by ruthenacyclopentene, (maleoyl)ruthenium, and rhodacyclopentenone intermediates. In addition, rhodium-catalyzed [2+2+2] cocyclization of alkynes with isocyanates as well as novel ruthenium-catalyzed [2+2+1] cocyclization of alkynes, isocyanates, and carbon monoxide have been disclosed. 1 Introduction 2 Ruthenium-Catalyzed Cycloaddition of Alkynes with Alkenes 2.1 [2+2] Cycloaddition of Alkynes with 2-Norbornenes 2.2 Intramolecular Pauson-Khand-Type Reaction of Enynes with Carbon Monoxide 2.3 Cross-Carbonylation of Alkynes with 2-Norbornenes or Electron-Deficient Alkenes to Hydroquinones 2.4 Synthesis of Benzenepolycarboxylates by Cross-Benzannulation of Acetylenedicarboxylates with Allylic Compounds 2.5 [2+2+2] Cocyclization of Three Different Alkynes 2.6 Regio- and Stereoselective Dimerization of Styrenes and Linear Codimerization of Styrenes with Ethylene 3 Ruthenium- and Rhodium-Catalyzed Cleavage of C-C Bonds Leading to Reconstructive Synthesis of Novel Functional Monomers 3.1 Ru-Catalyzed Selective Monodecarbonylative Coupling of Cyclobutenediones with Alkenes to Cyclopentenones 3.2 Ru-Catalyzed Carbonylative Dimerization of Cyclopropenones and Cross-Carbonylation of Cyclopropenones with Alkynes to Pyranopyrandiones 3.3 Ru- and Rh-Catalyzed Ring-Opening Reactions of Cyclobutenones 3.4 Rh-Catalyzed Direct Synthesis of Substituted Phenols from Cyclobutenones and Electron-Deficient Alkenes 4 Ruthenium- and Rhodium-Catalyzed Cocyclization of Alkynes and Isocyanates 4.1 Rh-Catalyzed Cyclocotrimerization of Alkynes and Isocyanates to 2-Pyridones or Pyrimidine-2,4-diones 4.2 Ru-Catalyzed [2+2+1] Cocyclization of Alkynes, Isocyanates, and Carbon Monoxide 5 Summary

A novel zerovalent ruthenium complex with a π-acidic ligand, Ru(η6-cyclooctatriene)(η2-dimethyl fumarate)2 (1), was prepared from Ru(η4-cyclooctadiene)(η6-cyclooctatriene) [Ru(cod)(cot)]. Complex 1 or Ru(cod)(cot) catalyzes various new carbon-carbon bond-forming reactions that include the [2 + 2] cycloaddition of alkenes and alkynes via ruthenacycles, the creation of a new hydrocarbon, pentacyclo[6.6.0.02,6.03,13.010,14]tetradeca-4,11-diene [PCTD], by dimerization of 2,5-norbornadiene via C-C bond cleavage, and the codimerization of alkynes and/or alkenes. Complex 1 was shown to be an excellent mother complex for various zerovalent ruthenium complexes. Complex 1 reacts with amines, phosphines or water to give new zerovalent ruthenium complexes with the ligands. The resulting aqua complexes have a water ligand with an oxygen atom that is a chiral center, i.e., ruthenium complexes with a ‘chiral water’ ligand were prepared and fully characterized.

Ruthenium complex-catalyzed reactions often require highly qualified tuning of reaction conditions with substrates to attain high yield and selectivity of the products. In this review, our strategies for achieving characteristic ruthenium complex-catalyzed co-oligomerization of different alkenes are disclosed: 1) The codimerization of 2-norbomenes with acrylic compounds by new ruthenium catalyst systems of RuCl 3 (tpy)/Zn [tpy = 2,2':6',2"-terpyridine] or [RuCl 2 (η 6 -C 6 H 6 )] 2 /Zn in alcohols, 2) A novel synthesis of 2-alkylidenetetrahydrofurans from dihydrofurans and acrylates by zerovalent ruthenium catalysts, such as Ru(η 4 -cod)(η 6 -cot) [cod = 1,5-cyclooctadiene, cot = 1,3,5-cyclooctatriene] and Ru( η 6 -cot)( η 2 -dmfm) 2 [dmfm = dimethyl fumarate], 3) Regio- and stereoselective synthesis of enamides by Ru(η 6 -cot)(η 2 -dmfm) 2 -catalyzed codimerization of N-vinylamides with alkenes, and 4) Unusual head-to-head dimerization of styrenes and linear codimerization of styrenes with ethylene by Ru(η 6 -cot)(η 2 -dmfm) 2 catalyst in the presence of primary alcohols.

A novel rhodium-catalyzed synthesis of substituted phenols by the ring-opening reaction of cyclobutenones with alkynes as well as electron-deficient alkenes has been developed. Both reactions involve C–C bond cleavage of cyclobutenones, and an (η4-vinylketene)rhodium complex rather than a rhodacyclopentenone is considered to be a key intermediate.