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DOI: 10.1002/adsc.201400940

Recent Advances in Transition Metal-Catalyzed Hydrogenationof Nitriles

Dattatraya B. Bagala and Bhalchandra M. Bhanagea,*a Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai 400 019, India

Fax: (++91)-22-24145614; phone: (++ 91)-22-3361-1111/2222; e-mail: [email protected] [email protected]

Received: September 25, 2014; Revised: November 25, 2014; Published online: January 22, 2015

Abstract: Amines are important building blocks pos-sessing various applications in agrochemicals, thefine chemical industry, pharmaceuticals, materialsscience and biotechnology. The catalytic hydrogena-tion of nitriles is an important reaction for the one-step synthesis of diverse amines. However, significantamounts of side product formation during the courseof the reaction is a major issue. In recent years, anenormous amount of work has been reported usingboth homogeneous and heterogeneous transitionmetal complex catalysts for the selective reduction ofnitriles. Transition metal catalysts are the most cru-cial factor that controls the selectivity in this reac-tion. Therefore, transition metal catalysts are thecentral point of this review. We have also briefly dis-cussed the effect of reaction parameters, selectivityto different substrate structures and reaction mecha-nisms. This review provides an overview of recent

developments in transition metal-catalyzed nitrile re-duction along with examples which highlight its vastpotential in organic transformations.

1 Introduction2 Catalytic Reductions of Nitriles2.1 Ruthenium2.2 Rhodium Complexes2.3 Palladium Complexes2.4 Iridium Complexes2.5 Platinum Complexes2.6 Other Transition Metal Complexes3 Conclusion and Outlook

Keywords: amines; chemoselectivity; heterogeneouscatalysis; homogeneous catalysis; hydrogenation; ni-triles

1 Introduction

Amines are versatile intermediates and precursors inthe synthesis of various natural products, pharmaceut-icals, dyes, pigments, agrochemicals and polymers.[1–4]

Among the amines, the terminal primary amines arethe most useful, but their selective synthesis is a chal-lenging task due to their high reactivity. In particular,the selective catalytic hydrogenation of nitriles repre-sents an atom-economic and valuable route to pri-mary amines. However, the reduction of nitriles tothe corresponding amines has been less investigatedso far compared to reductions of C=C, C=O, C=Nand NO2 bonds. This is primarily due to the highredox potential of nitriles compared to other carbox-ylic acid derivatives and the low C¢CN bond dissocia-tion energy, which leads to undesired reductive decya-nations, side reactions via fragmentation to alkyl radi-cals and cyanide anions; and the instability of imine/iminium intermediates under the reaction conditions,

which results in alcoholysis, transimination or reduc-tive polymerization pathways.[5]

Conventionally, nitriles are reduced using stoichio-metric amounts of metal hydrides,[6,7] either lithiumaluminium hydride (LiAlH4) at room temperature,sodium borohydride (NaBH4) at higher temperaturesor in the presence of heterogeneous catalysts basedon nickel,[8] palladium,[9] cobalt,[10] etc. Metal hydridereagents are effective, however; they are not environ-mentally benign due to the coproduction of stoichio-metric amounts of waste metal salts. The heterogene-ous metal catalysts demonstrate low selectivity to-wards primary amines and significant amounts of sec-ondary and tertiary amines are formed.[11] It also haslimitations with respect to functional group toleranceand the use of excess ammonia needed for high che-moselectivity.[12]

Hydrogenation of nitriles to primary amines (A) isusually accompanied by the formation of secondaryamines (B) and even tertiary amines (C) as shown inScheme 1. The reaction of the primary amine 3 with

Adv. Synth. Catal. 2015, 357, 883 – 900 Õ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 883

REVIEWS

the imine intermediate 2 gives the secondary imine 4with elimination of ammonia. Subsequent reductionof the secondary imine 4 gives the diamine 5. Further-more, the secondary amine reacts with the imine in-termediate 2 with exclusion of ammonia followed byreduction, which results in the formation of tertiaryamines 6. The formation of significant amounts ofside products such as secondary imines/amines andtertiary amines lowers the selectivity and overall atomefficiency of the reaction. The selectivity of the re-spective amines depends on the structure of the sub-strate, the nature and amount of the catalyst, basicand acidic additives, the reaction medium, and otherreaction parameters. Among these factors, the natureof the catalyst appears to be the most important for

determining the selectivity. Apparently, there are twopossibilities to improve the chemoselectivity towardsthe primary amine: (i) a low concentration of imine 2is desirable to suppress formation of the secondaryamine and (ii) the equilibrium between 2 and 4should be shifted towards 2 by the addition of ammo-nia or an appropriate base.

Until now, very few examples of an efficient reduc-tion of nitriles have been reported. There seems to beno review exclusively dedicated to the nitrile reduc-tion in the scientific literature with a comprehensiveand critical assessment of catalytic methods so far,except for the review published by Bellefon andFouilloux in 1994.[13] Recently, BellerÏs group pub-lished an excellent review entitled “Catalytic hydroge-

Dattatraya B. Bagal complet-ed his M.Sc. degree in organ-ic chemistry from the Univer-sity of Pune in 2008. Afterworking as a research chem-ist at Sai Life Sciences Ltd.Pune, India for two years, hemoved to the Institute ofChemical Technology (for-merly UDCT), Mumbai in2010 to begin his Ph.D. pro-gramme under the supervi-sion of Prof. Bhalchandra M. Bhanage. His Ph.D. re-search focuses on the development of greener cata-lytic systems for hydrogenation reactions. In 2012,he was awarded a DAAD research fellowship tocarry out research at the University of Regensburg,Germany with Prof. Oliver Reiser. At RegensburgUniversity he was engaged in the development ofnew chemical reactions using visible light photore-dox catalysis, with a particular focus on trifluorome-thylation reactions.

Bhalchandra M. Bhanage ob-tained his doctorate fromPune University in 1996. Hespent more than one year atTohoku University, Japan(1997–1998), and four yearsat Hokkaido University,Japan (2000–2003) as a post-doctoral fellow with Prof. M.Arai. In 2004, he joined theInstitute of Chemical Tech-nology, Mumbai, India asprofessor of industrial and engineering chemistry.His current research interest includes developingnovel catalytic systems for carbonylation, CO2 fixa-tion for valuable chemicals, hydrogenation, hydro-formylation, various coupling reactions, aminationreactions, etc. He is also working on nanomaterials,enzymatic catalysis and the use of non-conventionaltechniques like ultrasound and microwaves for vari-ous reactions.

Scheme 1. Hydrogenation of nitriles and possible side reactions.

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REVIEWSDattatraya B. Bagal and Bhalchandra M. Bhanage

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nation of carboxylic acid esters, amides, and nitrileswith homogeneous catalysts”, containing a short sec-tion on the catalytic reduction of nitriles.[14] However,they have not presented a comprehensive assessmentof the overall area of nitrile hydrogenation. More-over, nitrile reduction has been scarcely investigatedin comparison with C=C, C=N, and NO2 reductions.The various factors that control the selectivity, thelack of previous research, the low selectivity towardsprimary amines and the significant amounts of secon-dary amine formation, are the main reasons for this.Therefore, considering all these aspects, we describehere the recent developments in nitrile reduction withhomogeneous and heterogeneous transition metal cat-alyst in detail.

2 Catalytic Reductions of Nitriles

2.1 Ruthenium

Ruthenium complexes have attracted great attentionso far owing to their excellent performances in termsof activity and selectivity compared to other transitionmetals used for the catalytic hydrogenation of nitriles.

2.1.1 Ruthenium Complexes

Among the earliest reports, in 1969 Dewhirst dis-closed RuCl2(PPh3)3 and RuH2(PMePh2)4 as catalystsfor nitrile reduction.[15] Later, Bianchini and Psaro ex-plored the immobilised heterogeneous [(sulphos)-Ru(NCMe)3](OSO2CF3)/SiO2 7 and [(sulphos)-Ru(NCMe)3](OSO2CF3) 8 [(sulphos)=¢O3S(C6H4)-CH2C(CH2PPh2)3] as catalysts for the hydrogenationof benzonitrile.[16] On employing the silica-supportedheterogeneous complex 7 at 100 88C in THF as a sol-vent, the secondary imine was obtained as a majorproduct (87%). In contrast, on using homogeneouscomplex 8, the secondary amine was obtained in 65%yield along with the primary amine (34%). However,on decreasing the temperature to 70 88C, the secondaryimine was obtained exclusively in excellent yield(98%) within 1.5 h.

Later in 2002, Hidai and co-workers synthesisedamidoruthenium complexes 9, 10 and used them forthe selective reduction of benzonitrile in the presenceof PCy3 (PCy3 = tricyclohexylphosphine).[17] On apply-ing these complexes, benzylamine was obtained asa major product; however the presence of additionalbase (t-BuONa) improves the conversion (98%) andselectivity towards benzylamine (up to 92%). More-over, they observed that the product distribution wassignificantly affected by the substituent on the amideligand (Scheme 2).

Subsequently, BellerÏs group developed two appro-priate catalytic systems by applying [Ru(cod)-methyl-allyl]2 as precursor and DPPF [1,2-bis-(diphenylphos-phino)ferrocene] 11 or PPh3 (triphenylphosphine) 12as ligand for the hydrogenation of nitriles (Scheme 3and Scheme 4).[18,19] Various reaction parameters suchas the effect of various ruthenium precursors, differ-ent organic and inorganic bases, pressure and temper-ature were studied. The catalytic systems were appli-cable for the hydrogenation of various aromatic ni-triles with electron-donating and electron-withdraw-ing groups in ortho- and para-positions, heteroaromat-ic substrates as well as alkyl nitriles also giveexcellent yield and selectivity towards the primaryamine.

Furthermore, the same group explored the rutheni-um/N-heterocyclic carbene catalytic system for thehydrogenation of various nitriles at ambient condi-tions (Scheme 5).[20] This was the first example forRu/N-heterocyclic carbene-catalyzed selective reduc-tions of C�N triple bonds. To investigate the influenceof the ligand structure on the reduction of benzoni-trile, the authors studied various imidazolium salts asN-heterocyclic carbene precursors. The mesitylene-

Scheme 2. Hydrogenation of benzonitrile by amido-rutheni-um complexes.

Scheme 3. Reduction of nitriles by using an in situ generatedruthenium/DPPF catalytic system.

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REVIEWS Recent Advances in Transition Metal-Catalyzed Hydrogenation of Nitriles


based imidazolium salts (carbenes 1 and 2) gave thebest catalystic activity. Interestingly, further increasingthe bulkiness at the 2,6-positions of the aryl substitu-ent by isopropyl groups (carbenes 5 and 6) gave de-creased conversion. However, on changing the N-sub-stituent of the imidazolium salts from aryl to alkyl,

a decrease in the yield of benzyl amine was observed.Using the optimised reaction conditions, the hydroge-nation of substituted benzonitriles proceeded in goodto excellent yields under mild reaction conditions(40–80 88C) within 6–16 h. In particular, electron-richaryl nitriles are suitable substrates for this reaction.However, the substrate scope of the parent Ru/car-bene catalyst is lower compared to that of the Ru/phosphine systems.[18,19]

In 2012, Bruneau et al. explored for the first timethe use of ruthenium-benzylidene and ruthenium-in-denylidene catalysts for the selective hydrogenationof nitriles into the corresponding primary amines(Scheme 6).[21]

It was observed that the absence of base leads tothe reduction of olefinic bond; however the presenceof t-BuOK further favours the reduction of the nitrileto the amine and strongly inhibits the formation ofsecondary amines. The amount of catalyst used wasalso important in this conversion, when the amount ofcatalyst was lowered to 1 mol%, the reduction of thenitrile did not occur and only the olefinic bond wasfully hydrogenated. This result indicated that not onlythe presence of base was important, but also theamount of catalyst used in the reaction. These cata-

Scheme 4. Reduction of nitriles using the [Ru(cod)methyl-allyl]2/PPh3 catalyst.

Scheme 5. Ruthenium-catalyzed hydrogenation of nitriles by applying Ru/N-heterocyclic carbene complexes.




lysts are not only active for the hydrogenation of aro-matic nitriles but also for that of long-chain aliphaticnitriles. Their selective transformation from renewa-ble plant oil into industrially applicable a,w-linearamino esters in high yields has been achieved at 80 88Cunder 20 bar of hydrogen pressure with the additionof t-BuOK in the presence of catalyst 17.

In 2013, Beller and co-workers explored the selec-tive transfer hydrogenation of nitriles to the primaryamines catalyzed by the [{Ru(p-cymene)Cl2}2]/DPPBsystem.[22] Various reaction parameters such as the ef-fects of various phosphine ligands and the effects ofbases and different alcohols as hydrogen source werescreened. Among the alcohols, 2-butanol was foundto be the best hydrogen donor with a 79% yield ofthe primary amine. The catalytic system is applicablefor the transfer hydrogenation of a variety of aromat-ic and aliphatic nitriles giving good to excellent yieldsof the corresponding amines. The authors claim thatthe protocol is the most general transfer hydrogena-tion methodology demonstrated to date (Scheme 7).

Later in the same year, BellerÏs group investigatedthe domino ruthenium-catalysed transfer hydrogena-

tion of nitriles with subsequent N-monoalkylation byusing alcohols.[23] A variety of aromatic, heteroaro-matic, aliphatic, and disubstituted nitriles was con-verted with isopropanol into the secondary amineswith excellent yields of up to 99%. The effects of dif-ferent alcohols such as ethanol, 2-butanol, and 2-pen-tanol were studied on the transfer hydrogenation ofbenzonitrile, resulting in N-monoalkylation of benzo-nitrile to form the corresponding secondary amines inlow to excellent yields (Scheme 8). The proposedmechanism for the N-monoalkylation reaction pro-ceeds with hydrogenation of nitrile 19 by usingRuCl2(PPh3)3 with isopropanol and sodium hydroxideas the base to give primary amine 21. Whilst isopro-panol is dehydrogenated to acetone, the acetone fur-ther reacts with 21 through reductive amination togive the desired secondary imine 22 by releasingwater as a side product. Finally, imine 22 is subse-quently hydrogenated to furnish the desired secon-dary amine 20.

Following this work, recently Beller and co-workersreported the hydrogenation of various aliphatic andaromatic nitriles to the corresponding primary aminesin high to excellent yields.[24] The combination of[Ru(cod)(methylallyl)2] and imidazolylphosphine li-gands generate active homogeneous catalyst systems,which allow the hydrogenation of linear, branched,and cyclic aliphatic nitriles as well as aromatic nitriles(Scheme 9).

Scheme 6. Hydrogenation of benzonitrile and methyl (E)-11-cyanoundec-2-enoate catalyzed by ruthenium-alkylidenecomplexes.

Scheme 7. Transfer hydrogenation of nitriles with various al-cohols as hydrogen source.




2.1.2 Ruthenium Hydride Complexes

The early development in nitrile hydrogenationby ruthenium hydride catalysts was made byPez and Grey, using complexes[(Ph3P)Ph2P(C6H4)RuH2

¢K++(Et2O)·C10H18]2 25 and[(Ph3P)(Ph2P)RuH2

¢K++·diglyme]2 26.[25] Applyingthese complexes, substrates like acetonitrile, stearoni-trile, trimethylacetonitrile, and benzonitrile were hy-drogenated along with the ester. Later in 2004, Beattyand Paciello patented the nitrile hydrogenation using0.1 mol% of [RuH2(H2)2(PCy3)2] 27 at 50–70 bar H2

and a temperature between 80 and 100 88C.[26] In thesame year, Frediani and co-workers explored variousRu complexes RuH2(CO)2 [P(n-Bu)3]2 28,RuH2(CO)2(PPh3)2 29, and RuH2(PPh3)3 30 for thehydrogenation of nitriles.[27] However all these com-plexes provide N,N-dibenzylamine as a product inmoderate yield together with the primary amines.

In 2007, Morris and co-workers reported the use ofruthenium hydride complexes for the hydrogenationof benzonitrile.[28] They prepared the Ru hydride com-plex by treating RuHCl(PPh3)3 31 with {PPh2[(o-C6H4)CH2NHCH2]}2 32 in THF which resulted in anisomeric mixture of trans-RuHCl{ethP2(NH)2} 33(Scheme 10). After activation with t-BuOK, the com-plex 33 shows excellent activity for the hydrogenationof benzonitrile to benzylamine in toluene. Employingdihydrogen complex Ru(H2)2H2(PCy3)2 27 gives lessconversion as compared to complex 33.[26] Neverthe-less, when complex 27 is mixed with complex 33 or 34and base, it gives an excellent conversion thus making

Scheme 8. Ruthenium-catalyzed reduction and N-monoalky-lation of nitriles: substrate scope and reaction mechanism.

Scheme 9. Catalytic hydrogenation of various aromatic andaliphatic nitriles.

Scheme 10. Hydrogenation of benzonitrile with complexes33, 27 or 34.




an even more active system. The complexRuHCl{tmeP2(NH)2} 34 where tmeP2(NH)2 ={PPh2[(o-C6H4)CH2NHCMe2

¢]}2 is a less active cata-lyst for this reaction. It was also observed that addingKH as base to the reaction mixture using complex 33led to a shorter reaction time.

In 2010, the Sabo-Etienne group reported the hy-drogenation of benzonitrile into benzylamine cata-lyzed by a Ru bis(dihydrogen) complex incorporatingtricyclopentylphosphines under mild reaction condi-tions.[29] A series of experiments was performed atboth the stoichiometric and catalytic levels to gain in-formation on the mechanism of the nitrile reduction.It was observed that precatalyst 35 is converted withone or two equivalents of benzonitrile to give the cor-responding cyclometallated imine complexes 36 and38 as the resting state of the catalyst (Scheme 11). Akey step in this system is ortho-directed C¢H activa-tion within the aryl group, which induces fast cyclo-metallation and trapping of the intermediate imine togenerate 38. The reduction of benzonitrile to benzyla-mine was achieved successfully with complexes 35,36 and 38 under mild reaction conditions(Table 1). However, the dihydride complex

RuH2(PhCN)2(PCyp3)2 37 was difficult to isolate andwas readily converted to 38 at ambient temperature.

Leitner and co-workers investigated a rutheniumhydride complex with pincer ligands for nitrile reduc-tion.[30] With this catalytic system, various aliphaticand aromatic nitriles were hydrogenated to the corre-sponding primary amines in 36–96% yield under opti-mised reaction conditions. To furnish this conversion,relatively high pressure, high temperature, and longreaction time were necessary. It was observed that ad-dition of a small amount of water (5 equiv. relative tothe catalyst) provided increased conversions and se-lectivity towards primary amines (Scheme 12).

In 2014, Williams and co-workers reported a ruthe-nium bis(pyrazolyl)borate scaffold 40 that enables co-operative reduction reactivity in which boron andruthenium centres work in concert to effect selectivenitrile reduction.[31] Various aromatic, aliphatic, andheterocyclic nitriles are smoothly reduced to corre-sponding primary amines under the optimised condi-tions (Scheme 13A). Both electron-poor and electron-rich substrates can be reduced in high yield. Ketonegroups are known to react with NaBH4, the reductionof nitriles in the presence of ketone group illustratesthe high-yielding double reduction for the synthesis ofamino alcohols. A similar double reduction is ob-served in the reaction of a,b-unsaturated nitriles togive alkylamines. Reactions of nitriles appended to ar-omatic heterocycles afforded complicated results. Forexample, pyridine is compatible with the conditions.In contrast, more electron-rich heterocyclic systemsare not reduced but rather selectively monohydrated

Scheme 11. Hydrogenation of benzonitrile by complex 35.

Table 1. Hydrogenation of benzonitrile (BN) towards ben-zylamine (I) and dibenzylimine (II).[a]

Conv. of BN [%] Product Ratio of I:IICatalyst Solvent 2 h 24 h 2 h 24 h

35 pentane 94 94 94:6 94:635 THF 56 96 96:4 99:135[b] THF 62 98 22:77 96:435 none 84 97 0.1:99.9 89:1136 THF 68 97 96:4 99:138 THF 68 96 98:2 99:1

[a] Catalyst 35, 36 or 38 (0.5 mol%), 22 88C, 3 bar H2, THF.[b] 0.2 mol% catalyst.

Scheme 12. Hydrogenation of nitriles with the non-classicalruthenium hydride pincer complex.




giving the corresponding amides. The mechanism forthese reactions involves the addition of methanol (sol-vent) to a ruthenium-coordinated nitrile, and theamide products are formed upon aqueous work-up.Furthermore, this platform has yielded new insightsinto the cooperative reactivity of ruthenium andboron by showing a plausible scenario of how thesetwo centres can work together as an activating group(ruthenium) and a hydride donor (boron)(Scheme 13A).

In the plausible reaction mechanism, the bridgingamine ligand is replaced by an incoming substrate,and the borohydride group of 43 is regenerated bya hydride from NaBH4 (Scheme 13B). It was observedby 1H coupled 11B NMR spectroscopy that treatmentof 41 with a stoichiometric portion of NaBH4 inMeOH-d4 results in the formation of (MeO)4B, un-reacted BH4 and a catalyst doublet, which indicatesthat a (pz)2BH2 43 intermediate is formed.

2.2 Rhodium Complexes

In 1979, Yoshida, Okano, and Otsuk explored rhodi-um(I) hydrides for the first time for the selective hy-drogenation of nitriles to the corresponding primaryamines under ambient conditions.[32] Using RhH[P(i-Pr)3]3 44 and Rh2H2(m-N2{P(cyclohexyl)3}4 45 variousaromatic and aliphatic nitriles could be hydrogenatedto the amines with excellent yield (up to >99%). Itwas observed that complex 45 is less efficient thancomplex 44 under the optimised reaction conditions.On applying complex 45 for the hydrogenation ofa,b- and b,g-unsaturated nitriles, the olefinic bondwas reduced more readily than that of the nitrilegroup (Scheme 14).

In 2004, EckertÏs group explored the Rh complex44 for the selective reduction of benzonitrile and phe-nylacetonitrile in THF and CO2-expanded THF atroom temperature by molecular hydrogen.[33] It was

Scheme 13. A) Ruthenium bis(pyrazolyl)borate-catalyzed reduction of nitriles. B) Proposed reaction mechanism for nitrilereductions.




observed that, employing benzonitrile as substrate,the yield of the primary amine was increased by theaddition of CO2 (Table 2). The increase of primaryamine yield under CO2 pressure may be due to the insitu separation of the primary amine from the metalcentre, which remains in solution. The carbamic acidand/or ammonium carbamates formed under CO2

pressure during the course of the reaction were sepa-rated as a white solid and the homogeneous catalystremained in the solution.

2.3 Palladium Complexes

In 2005, the group of Hegedîs reported the liquid-phase heterogeneous catalytic hydrogenation of ben-zonitrile (BN) to benzylamine (BA) under mild reac-tion conditions.[34] The catalytic system works undermild reaction condition over supported palladium cat-alysts (Pd/C), in a mixture of two immiscible solvents(e.g., water/dichloromethane) and in the presenceof sodium dihydrogen phosphate (NaH2PO4)(Scheme 15). The effects of various reaction parame-ters such as the acidic additives, different supportedPd catalysts, the catalyst concentration, organic sol-vents, the pressure and the temperature have been

studied in detail. It was observed that the amount ofacidic additive, the type of organic solvent, the palla-dium metal and the temperature determine the selec-tivity to the primary amine in this hydrogenation.

Later in 2008, the same group reported the selec-tive reduction of benzyl cyanide to 2-phenylethyl-amine over palladium on carbon at 40 88C and 6 barhydrogen pressure.[35] Under the optimised reactionconditions complete conversion of benzyl cyanide wasobserved, however, lower isolated yield (40%) and se-lectivity (45%) to primary amine were achieved thanin the previous report on benzonitrile reduction.[34]

The lower yield and selectivity to 2-phenylethylaminewas due to the weak adsorption of the 2-phenylethyli-mine on Pd(111) compared to benzaldimine and alsodue to the different structures of their minimal energyconformers.

For the first time, the use of supercritical carbon di-oxide (scCO2) in the hydrogenation of benzonitrileover Pd and other metal catalysts was explored byChatterjee and Kawanami.[36] Without any additive,benzonitrile was hydrogenated to benzylamine withhigh conversion (90.2%) and selectivity (90.9%) usingthe Pd/MCM-41 46 as a catalyst (Scheme 16). Theproduct distribution was found to depend on differentreaction parameters such as CO2 and H2 pressures,temperature and the nature of the support. Simpletuning of the CO2 pressure resulted in the formation

Scheme 14. Hydrogenation of nitriles by complex 44 and 45.

Table 2. Rh-catalyzed hydrogenation of benzonitrile andphenylacetonitrile in THF and CO2-expanded THF.[a]

Substrate CO2 Pressure [bar] Yield [%]

benzonitrile 0 47benzonitrile 20 61phenylacetonitrile 0 95phenylacetonitrile 20 96

[a] Reaction conditions: catalyst 44 (0.01 mmol), THF, H2

(20 bar), temperature 23–25 88C, 20 h.

Scheme 15. Hydrogenation of benzonitrile to benzylamine.

Scheme 16. Hydrogenation of different nitriles in scCO2.




of the secondary amine, dibenzylamine, which was as-sisted by the interaction of CO2 with the reactant andalso by an acidic support for carbon, instead of theneutral MCM-41. Under the studied experimentalconditions, Pd/C was deactivated easily; whereas com-plex 46 can be reused for up to 5 recycle runs(Figure 1).

In 2012, Wang and co-workers reported the highlyefficient heterogeneous Pd@mpg-C3N4 47 catalyticsystem for selective reduction of nitriles providinggood to excellent conversion with remarkable selec-tivity (up to 99%) without additives.[37] On employingcomplex 47 under optimized reaction conditions, ali-phatic nitriles give selectively the tertiary amines,except for cyclohexanecarbonitrile which gives thesecondary amine in 99% selectivity, whereas aryl ni-triles lead the formation of secondary amines(Scheme 17). These authors have also screened vari-ous heterogeneous Pd catalysts such as Pd/TiO2, Pd/CeO2 and Pd/Al2O3 which result in the formation ofsecondary amines as the major product. The devel-oped protocol is more advantageous due to the use of

ambient hydrogen (1.0 MPa H2), solvent free reactionand effective catalyst recyclability (up to 4 times)compared with homogeneous catalyst systems(Figure 2).

Arai and co-workers reported the hydrogenation ofbenzonitriles by Pd/Al2O3 48 in the presence of pres-surised CO2 and H2O.[38] It was observed that the se-lectivity for benzylamine was enhanced significantlyin the presence of CO2 and water. However, in ab-sence of CO2 and water, full conversion of benzoni-trile was observed with lower selectivity towards ben-zylamine.

Notably, the absence of water in reaction mediumled to deactivation of the catalyst by accumulation ofcarbamate salt on the surface of the catalyst. The de-veloped catalytic system is advantageous due to theselective production of benzylamine in different sol-

Figure 1. Effect of CO2 pressure on the conversion and se-lectivity of benzonitrile hydrogenation over a) Pd/MCM-41and b) Pd/C. (Reproduced from ref.[36] with permission ofThe Royal Society of Chemistry).

Scheme 17. Hydrogenation of nitriles catalyzed by complex47.

Figure 2. Recyclability study of complex 47 for hydrogena-tion of butyronitrile. (Reproduced from ref.[37] with permis-sion of Elsevier).




vents without loss of the catalytic activity by the pal-ladium catalyst.

More recently, BellerÏs group reported the catalytictransfer hydrogenation of aromatic nitriles to the cor-responding primary amines catalyzed by commerciallyavailable 10% Pd/C 49 as a heterogeneous catalystusing HCO2H-NEt3 as hydrogen donor.[39] The cata-lytic system is applicable for the reduction of a varietyof different aromatic and heteroaromatic nitriles. Theprotocol excludes the use of an autoclave, any addi-tives and the reaction proceeds smoothly under mildconditions giving moderate to excellent yields. Re-markably, related functional groups such as amidesand esters were not affected under the optimised con-ditions, thus allowing the synthesis of interesting bi-functional building blocks. However, the present pro-tocol was not applicable for the reduction of aliphaticnitriles (Scheme 18).

2.4 Iridium Complexes

The first iridium-catalyzed hydrogenation of aromaticand aliphatic nitriles was reported by Chin andLee.[40] Various iridium complexes such as [Ir-(cod)(PPh3)(PhCN)2]ClO4 50, [Ir(cod)(PPh3)2]ClO4

51, and [Ir(cod)(PhCN)2]ClO4 52 were examined fornitrile reduction in different solvents, such as di-chloromethane, methanol, and benzene, Howevera mixture of primary, secondary and tertiary amineswas observed. The hydrogenation of nitriles in DCMas solvent is more efficient as compared to that in

other polar and non-polar solvents. This may be un-derstood by the formation of non-coordinating ami-ne·HCl salts in CH2Cl2 which cannot be formed inother solvents. Employing complex 51, the hydroge-nation of benzonitriles led to the formation of the ter-tiary amine with good selectivity and conversion.Moreover, during reaction with complex 52, decom-position of 52 occurred forming metallic iridium pow-ders in combination with molecular hydrogen. There-fore, iridium metal and probably nanoparticles wereformed, which are responsible for the further reduc-tion of the phenyl ring of benzonitrile.

2.5 Platinum Complexes

Unlike other transition metal-catalyzed reductions ofnitriles, Gu and co-workers explored the Pt nanowiresas a catalyst for the selective synthesis of secondaryamines via reductive amination of the correspondingnitriles.[41] This catalytic system allows the synthesis ofboth unsymmetrical and symmetrical secondaryamines in excellent yields (up to 95%) in the presenceor absence of additional amines, respectively.

The reaction mechanism shows a reaction betweenthe formed primary amine and the intermediate imineaccompanied by the expulsion of ammonia, which cangive rise to a secondary amine; however, when the in-termediate imine couples with an aliphatic amine itgives the corresponding unsymmetrical amine(Scheme 19).

2.6 Other Transition Metal Complexes

Besides the platinum group metals, recently othertransition metal species have also been developed aseffective catalysts for the selective hydrogenation ofnitriles. In 2009, Lemaire and co-workers reporteda simple and efficient method for the reduction of ni-triles into the corresponding amines (HCl salts) inalmost quantitative yield using a tetramethyldisilox-ane/titanium(IV) isopropoxide reducing system.[42]

The protocol uses TMDS and Ti(O-i-Pr)4 in stoichio-metric quantities for the reduction of nitriles. Theacidic work-up allows one to isolate the amine bycrystallization of the hydrochloride salt (Scheme 20).

In 2011 Berke et al. reported the homogeneous rhe-nium(I) nitrosyl complexes for the hydrogenation ofnitriles to the corresponding symmetrical secondaryamines or tertiary amines using triethylsilane as hy-drogen source.[43] A series of novel rhenium(I) cata-lysts (complexes 55, 56, 59, and 60) was prepared withthe large bite angle sixantphos ligands 53, 54 and theproducts were tested for the hydrogenation of nitrilesto the corresponding symmetrical secondary amines(Scheme 21). It was observed that the addition of tri-

Scheme 18. Palladium on carbon (Pd/C)-catalyzed transferhydrogenation of (hetero)aromatic nitriles.




ethylsilane could increase the TOFs and suppressover-alkylation of the amines at higher pressures witha relatively high loading of the catalyst (Table 3).

Later in the same year, Cabrita and Fernandes re-ported the PhSiH3/ReIO2(PPh3)2 catalytic system forthe reduction of nitriles to the corresponding primaryamines.[44] The complex ReIO2(PPh3)2 61 is highlystable towards air and moisture. The complex 61 isapplicable for reduction of various nitriles in the pres-ence of a wide range of functional groups such as Cl,F, Br, I, CF3, OCH3, SCH3, SO2CH3 and NHTs(Scheme 22).

Scheme 19. Formation of symmetrical and unsymmetrical secondary amines from different nitriles.

Scheme 20. TMDS reduction of nitriles to amines.

Scheme 21. Complexes 55 and 56 and their splitting equili-bria with 57 and 58, respectively, in acetonitrile. Structure ofthe diastereomers A and B of 59 and 60.




In 2012, Singaram and co-workers reported the re-duction of various aromatic and aliphatic nitriles byusing HInCl2 62 via the in situ reduction of InCl3

using lithium aminoborohydride.[45] The reported pro-tocol is simple, efficient and works under milder reac-tion conditions for the reduction of aromatic, hetero-aromatic, benzylic, and aliphatic nitriles to the corre-sponding primary amines using the in-situ generatedBH3·THF (Scheme 23A). Additionally, it was demon-strated that halides and nitrile functionalities can bereduced in tandem by making use of the reductive ca-pabilities of both HInCl2 and BH3·THF reducingagents. This was demonstrated by reducing 4-(bromo-methyl)benzonitrile to the corresponding 4-methyl-benzylamine with an isolated yield of 61%. Selectivereduction of halides in the presence of nitriles was

achieved by using either InCl3/NaBH4 in CH3CN orInCl3/MeLAB (MeLab= lithium dimethylaminoboro-hydride) in THF (Scheme 23B).

The photostimulated reduction of various nitrilescatalyzed by SmI2 63 has been reported by the Hozgroup.[46] They studied the reactivity of aliphatic, aro-matic and dicyano compounds using photostimulationin the visible region. MeOH (0.2 M) is used as theproton donor which complexes efficiently with SmI2

resulting in formation of the corresponding amine.The mechanism of the reaction involves coordinationof the SmI2 to the lone pair of the nitrile nitrogen fol-lowed by an inner sphere electron transfer. This is

Table 3. Hydrogenation of nitriles catalyzed by complexes55, 56, 59 and 60.

Entry Nitrile Catalyst Yield [%] TOF [h¢1]

1 Ph 55 85 1982 Ph 56 86 1983 Ph 59 90 1984 Ph 60 82 1965 3-tolyl 55 89 1986 3-tolyl 56 87 1987 2-thienyl 59 83 1628 2-thienyl 60 85 1609 3-tolyl 59 81 17010 3-tolyl 60 80 16911 PhCH2 55 10 17612 cyclohexyl 55 95 198

[a] 0.5 mol% of catalyst with 25 equiv. of triethylsilane withrespect to catalyst at 75 bar H2, 140 88C in THF, 1 h.

Scheme 22. Reduction of nitriles catalyzed by complex 61.

Scheme 23. A) InCl3/NaBH4 reduction of various nitriles toprimary amines. B) Selective reductions of the carbon–bro-mine bond by InCl3/LAB.

Scheme 24. Photostimulated reduction of various nitrilescatalyzed by SmI2.




evidenced by the dependence of the yield on theMeOH concentration. As the concentration of theMeOH increases, it complexes the SmI2 more inten-sively and prevents coordination to the nitrogen lonepair. As a result, the yield goes down (Scheme 24).

Copper, an abundant and inexpensive metal com-pared to noble metals, has not been well explored fornitrile reduction until now. In this regard, Branco andco-workers for the first time reported a copper-cata-lyzed gas-phase hydrogenation of propionitrile to thecorrosponding primary amine, i.e., propylamine asmajor product.[47,48] Later in 2013, Burri et al. reportedthe selective reduction of benzonitrile to benzylamineusing Cu-MgO catalysts in the absence of any addi-tives at atmospheric pressure.[48] They have preparedthe Cu-MgO catalyst by impregnating a freshly pre-pared MgO support using Cu(NO3)2·3 H2O as Cu pre-cursor with Cu loadings of 4, 8, 12 and 16%, respec-tively (Figure 3). Among them, the 12% Cu-MgO cat-alyst shows excellent activity with 98% conversionwith 70% selectivity of benzylamine at 513 K. Worthyof mention is that up to 100% selectivity towards the

Figure 3. Influence of Cu loading in Cu-MgO catalysts to-wards the hydrogenation of benzonitrile at 473 K withWHSV (weight hourly space velocity) of 1 h¢1. (Reproducedfrom ref.[48] with permission of Elsevier).

Scheme 25. Electron transfer reduction of nitriles using SmI2-Et3N-H2O.

Scheme 26. Reduction of nitriles with NiNPs@Fe3O4-SiO2-P4VP MGs as the catalyst system.




primary amine was achieved under the optimized con-ditions using 12% Cu-MgO catalysts at 1 atmosphericpressure with a WHSV (weight hourly space velocity)of 1 h¢1.

Procter and co-workers reported the reduction ofnitriles to the corresponding primary amines undersingle electron transfer conditions using complex 63(KaganÏs reagent) activated with Lewis bases.[50] Thecatalytic system features excellent functional grouptolerance and represents an attractive alternative tothe use of pyrophoric alkali metal hydrides. The pro-posed mechanism shows that the reaction proceedsthrough the generation of imodoyl-type radicalswhich form an equilibrium with the amine radical.Subsequently single electron transfer (SET) to theradical imine generates a carbamine anion, which un-dergoes a protonation resulting in the formation of

the imine. In next step, a further SET to the imineleads to the formation of an Sm3++ intermediate whichupon subsequent protonation furnishes the final prod-uct (Scheme 25).

In 2014, Nabid et al. reported the reduction of ali-phatic and aromatic nitriles using NiNPs@Fe3O4-SiO2-P4VP 64 as an efficient catalyst (Scheme 26).[51] Thecatalyst is applicable for the reduction of both aro-matic and aliphatic nitriles in excellent yields. Thecatalyst can be recycled for up to seven cycles bymagnetic separation without loss in activity and selec-tivity. The catalytic system has the advantages of flexi-

Figure 4. Effect of recycling on the catalytic activity andproductivity of NiNPs@Fe3O4-SiO2-P4 VP MGs after a)30 min (black) and b) 2 h (grey). (Reproduced from ref.[51]

with permission of John Wiley & Sons).

Scheme 27. Hydrogenation of aromatic and aliphatic nitriles catalyzed by complexes 65 and 66.

Figure 5. Proposed reaction mechanism: nitrile hydrogena-tion by pincer PNP iron complex.




bility and practicality, a simple work-up process, andeasy recovery of the catalyst, and thus it can be usedfor the reduction of many different carbon-nitrogenmultiple bonds. Analysis of the complex showed goodstability and recyclability, as the conversion yields forseven runs after 30 min did not decrease significantly.In addition, to investigate the productivity of the pre-pared catalyst, they examined the reduction of benzo-nitrile for seven cycles even after the completion ofthe reaction (Figure 4).

The results shown in Figure 4b demonstrate that,after every run, the product yield does not change sig-nificantly, which indicates the high productivity of thecatalyst.

Berke et al. demonstrated the use of low-valentmolybdenum 65 and tungsten 66 amides as active cat-alysts for the hydrogenation of various nitriles to thecorresponding secondary imines.[52] A wide range of

para- and meta-substituted aromatic nitriles, the heter-ocyclic 2-thiophencarbonitrile and aliphatic nitrilescould be hydrogenated giving high yields and appreci-able selectivity towards secondary imines along withthe formation of primary imines and the primaryamines. Both complexes 65 and 66 were applied fornitrile reduction without adding any additives/co-cata-lysts under homogeneous conditions. However com-plex 65 attains excellent conversions compared tocomplex 66. The developed catalytic system repre-sents a promising alternative to the precious groupmetal catalysts (Scheme 27).

The very first selective nitrile hydrogenation viaa non-precious metal pincer-type PNP iron catalystunder relatively milder reaction conditions was ac-complished recently by Beller and co-workers. Underthe optimised conditions, various aromatic and ali-phatic (di)nitriles were converted to the correspond-

Scheme 28. Hydrogenation of various aromatic nitriles by complex 67.




ing primary amines (as HCl salts) in good to excellentyields using an iron PNP pincer complex.[53] The cata-lytic system shows excellent functional group toler-ance. Ester, ether, acetamido as well as amino sub-stituents are not reduced in the presence of nitriles.Moreover, nitriles including an a,b-unsaturateddouble bond and halogenated derivatives are well tol-erated in this reaction. The reaction is proposed toproceed first with catalyst activation (Figure 5); it wasassumed that the loss of BH3 gives complex 71. Then,the nitrile is hydrogenated in a concerted way by a si-multaneous transfer of the hydride from the ironcenter and the proton from the nitrogen ligand togive the corresponding imine 73 and the amido com-plex 72. The dihydrido species 71 is regenerated bythe addition of molecular hydrogen. The imine 73 un-dergoes a second reaction cycle and is finally reducedto the corresponding amine 69 (Scheme 28).

3 Conclusion and Outlook

The efficient and selective conversion of nitriles intoprimary amines is a challenging task and catalystsplay a key role in selectivity for this transformation.Indeed, numerous new catalytic systems for nitrile re-duction have been actively developed in the lastdecade. In this perspective, we have reviewed themost recent progress in transition metal-catalyzed ni-trile reduction. Although the reactivity of nitriles islower compared to that of C=C, C=O, C=N and NO2

bonds, the efficiency of transition metal catalysts isfar better than that of metal hydrides. The catalyticreduction of nitriles to the corresponding primaryamines is highly atom-efficient; however formation ofby-products such as secondary imines/amines reducesthe significance. Nevertheless, some of the catalystsrecently developed showed high activity and excellentselectivity towards primary amines. Selectivity to-wards primary amines, the catalyst-product separationand catalyst recyclability are the major problems andthere is a need for the development of various novelstrategies to solve these problems. Further develop-ments toward the selective synthesis of primaryamines from nitriles using environmentally benignand milder reaction conditions are expected.

Acknowledgements

The authors (D. B. Bagal) express gratitude towards Univer-sity Grant Commission, New Delhi, India (UGC-SAP) forproviding a senior research fellowship.

References

[1] a) A. Ricci, Modern Amination Methods, Wiley, Wein-heim, 2000 ; b) J. S. Carey, D. Laffan, C. Thomson,M. T. Williams, Org. Biomol. Chem. 2006, 4, 2337–2347; c) K. Eller, E. Henkes, R. Rossbacher, H. Hçke,in: UllmannÏs Encyclopedia of Industrial Chemistry,Vol. A2, Wiley-VCH, Weinheim, 2008, p 2J.

[2] a) J. Seayad, A. Tillack, C. G. Hartung, M. Beller, Adv.Synth. Catal. 2002, 344, 795–813; b) F. Pohlki, S. Doye,Chem. Soc. Rev. 2003, 32, 104–114; c) W. Tang, X.Zhang, Chem. Rev. 2003, 103, 3029–3069; d) N. Fleury-Bregeot, V. de La Fuente, S. Castillon, C. Claver,ChemCatChem 2010, 2, 1346–1371; e) R. Severin, S.Doye, Chem. Soc. Rev. 2007, 36, 1407–1420.

[3] a) S. T. McMillan, P. K. Agrawal, Ind. Eng. Chem. Res.1988, 27, 243–248; b) T. E. Mueller, K. C. Hultzsch, M.Yus, F. Foubelo, M. Tada, Chem. Soc. Rev. 2008, 37,3795–3892; c) T. C. Nugent, M. El-Shazly, Adv. Synth.Catal. 2010, 352, 753–819; d) M. Rueping, E. Sugiono,F. R. Schoepke, Synlett 2010, 6, 852–865.

[4] a) K. Hayes, Appl. Catal. A 2001, 221, 187–195;b) Amines: Synthesis Properties and Application, (Ed.:S. A. Lawrence), Cambridge University Press, Cam-bridge, 2004, p 50; c) D. B. Bagal, R. A. Watile, M. V.Khedkar, K. P. Dhake, B. M. Bhanage, Catal. Sci. Tech-nol. 2012, 2, 354–358; d) M. D. Bhor, M. J. Bhanushali,N. S. Nandurkar, B. M. Bhanage, Tetrahedron Lett.2008, 49, 965–969; e) M. J. Bhanushali, N. S. Nandurkar,M. D. Bhor, B. M. Bhanage, Tetrahedron Lett. 2007, 48,1273–1276; f) Y. S. Wagh, P. J. Tambade, D. N. Sawant,B. M. Bhanage, Eur. J. Org. Chem. 2010, 26, 5071–5076;g) Y. S. Wagh, D. N. Sawant, K. P. Dhake, B. M. Bhan-age, Catal. Sci. Technol. 2012, 2, 835–840.

[5] a) D. J. Procter, R. A. Flowers II, T. Skrydstrup, Or-ganic Synthesis Using Samarium Diiodide: A PracticalGuide, RSC Publishing, Cambridge, 2009 ; b) H. B.Kagan, Tetrahedron 2003, 59, 10351–10372; c) D. J. Ed-monds, D. Johnston, D. Procter, Chem. Rev. 2004, 104,3371–3404; d) K. C. Nicolaou, S. P. Ellery, J. S. Chen,Angew. Chem. 2009, 121, 7276–7301; Angew. Chem. Int.Ed. 2009, 48, 7140–7165; e) M. Szostak, D. J. Procter,Angew. Chem. 2011, 123, 7881–7883; Angew. Chem.Int. Ed. 2011, 50, 7737–7739; f) M. Szostak, M. Spain,D. J. Procter, Chem. Soc. Rev. 2013, 42, 9155–9183.

[6] a) L. H. Amundsen, L. S. Nelson, J. Am. Chem. Soc.1951, 73, 242–244; b) D. Haddenham, L. Pasumansky, J.DeSoto, S. Eagon, B. Singaram, J. Org. Chem. 2009, 74,1964–1970; c) J. Z. Saavedra, A. Resendez, A. Rovira,S. Eagon, D. Haddenham, B. Singaram, J. Org. Chem.2012, 77, 221–228; d) S. Caddick, A. K. de K. Haynes,D. B. Judd, M. R. V. Williams, Tetrahedron Lett. 2000,41, 3513–3516; e) Comprehensive Organic Synthesis,(Eds.: B. M. Trost, I. Fleming), Pergamon Press, NewYork, 1991; f) M. Hudlicky, Reductions in OrganicChemistry, Ellis Horwood, Chichester, 1984 ; g) J.Seyden-Penne, Reductions by the Alumino- and Boro-hydrides in Organic Synthesis, Wiley, New York, 1997;h) P. G. Andersson, I. J. Munslow, Modern ReductionMethods, Wiley-VCH, Weinheim, 2008.

[7] D. Haddenham, L. Pasumansky, J. DeSoto, S. Eagon, B.Singaram, J. Org. Chem. 2009, 74, 1964–1970.




[8] a) C. V. Rode, M. Arai, M. Shirai, Y. Nishiyama, Appl.Catal. A 1997, 148, 405–413; b) S. Caddick, D. B. Judd,A. K. de K. Lewis, M. T. Reich, M. R. V. Williams, Tet-rahedron 2003, 59, 5417–5423; c) P. Zerecero-Silva, I.Jimenez-Solar, M. G. Crestani, A. Ar¦valo, R. Barrios-Francisco, J. J. Garc�a, Appl. Catal. A 2009, 363, 230–234; d) P. Kukula, M. Studer, H. Blaser, Adv. Synth.Catal. 2004, 346, 1487–1493; e) S. Caddick, A. K. de K.Haynes, D. B. Judd, M. R. V. Williams, TetrahedronLett. 2000, 41, 3513–3516.

[9] a) B. Klenke, I. H. Gilbert, J. Org. Chem. 2001, 66,2480–2483; b) Y. Huang, W. M. H. Sachtler, Appl.Catal. A 1999, 182, 365–378; c) Y. M. Lopez-De Jesus,C. E. Johnson, J. R. Monnier, C. T. Williams, Top Catal2010, 53, 1132–1137.

[10] a) B. Ganem, S. W. Heinzman, J. Am. Chem. Soc. 1982,104, 6801–6802; b) P. L. Beaulieu, P. W. Schiller, Tetra-hedron Lett. 1988, 29, 2019–2022; c) J. G. Buchanan,K. W. Lumbard, R. J. Sturgeon, D. K. Thompson, R. H.Wightman, J. Chem. Soc. Perkin Trans. 1 1990, 699–706; d) K. Chantrapromma, B. Ganem, J. S. McManis,Tetrahedron Lett. 1980, 21, 2475–2476; e) D. F. Covey,J. A. Ferrendelli, M. W. Hill, B. C. H. Hsiang, T. N.Latifi, P. A. Reddy, S. M. Rothman, K. E. Woodward, J.Med. Chem. 1996, 39, 1898–1906.

[11] a) S. Galvagno, A. Donato, G. Neri, R. Pietropaolo, J.Mol. Catal. 1990, 58, 215–225; b) D. J. Segobia, A. F.Trasarti, C. R. Apestegu�a, Appl. Catal. A 2012, 445–446, 69–75.

[12] a) S. Gomez, J. A. Peters, T. Maschmeyer, Adv. Synth.Catal. 2002, 344, 1037–1057; b) P. Kukula, M. Studer,H. Blaser, Adv. Synth. Catal. 2004, 346, 1487–1493.

[13] C. de Bellefon, P. Fouilloux, Catal. Rev. Sci. Eng. 1994,36, 459–506.

[14] S. Werkmeister, K. Junge, M. Beller, Org. Process Res.Dev. 2014, 18, 289–302.

[15] K. C. Dewhirst, (assigned to Shell Oil Co.), U.S. Patent3,454,644, 1969.

[16] C. Bianchini, V. Dal Sant, A. Meli, W. Oberhauser, R.Psaro, F. Vizza, Organometallics 2000, 19, 2433–2444.

[17] S. Takemoto, H. Kawamura, Y. Yamada, T. Okada, A.Ono, E. Yoshikawa, Y. Mizobe, M. Hidai, Organome-tallics 2002, 21, 3897–3904.

[18] S. Enthaler, D. Addis, K. Junge, G. Erre, M. Beller,Chem. Eur. J. 2008, 14, 9491–9494.

[19] S. Enthaler, K. Junge, D. Addis, G. Erre, M. Beller,ChemSusChem 2008, 1, 1006–1010.

[20] D. Addis, S. Enthaler, K. Junge, B. Wendt, M. Beller,Tetrahedron Lett. 2009, 50, 3654–3656.

[21] X. Miao, J. Bidange, P. H. Dixneuf, C. Fischmeister, C.Bruneau, J.-L. Dubois, J.-L. Couturier, ChemCatChem2012, 4, 1911–1916.

[22] S. Werkmeister, C. Bornschein, K. Junge, M. Beller,Chem. Eur. J. 2013, 19, 4437–4440.

[23] S. Werkmeister, C. Bornschein, K. Junge, M. Beller,Eur. J. Org. Chem. 2013, 3671–3674.

[24] S. Werkmeister, K. Junge, B. Wendt, A. Spannenberg,H. Jiao, C. Bornschein, M. Beller, Chem. Eur. J. 2014,20, 4227–4231.

[25] R. A. Grey, G. P. Pez, A. Wallo, J. Am. Chem. Soc.1981, 103, 7536–7542.

[26] R. P. Beatty, R. A. Paciello, WO Patent WO/1996/23802-804, 1996.

[27] A. Toti, P. Frediani, A. Salvini, L. Rosi, C. Giolli, C.Giannelli, C. R. Chim. 2004, 7, 769.

[28] T. Li, I. Bergner, F. N. Haque, M. Z. Iuliis, D. Song,R. H. Morris, Organometallics 2007, 26, 5940–5949.

[29] R. Reguillo, M. Grellier, N. Vautravers, L. Vendier, S.Sabo-Etienne, J. Am. Chem. Soc. 2010, 132, 7854–7855.

[30] C. Gunanathan, M. Hçlscher, W. Leitner, Eur. J. Inorg.Chem. 2011, 3381–3386.

[31] Z. Lu, T. J. Williams, Chem. Commun. 2014, 50, 5391–5393.

[32] T. Yoshida, T. Okano, S. Otsuka, J. Chem. Soc. Chem.Commun. 1979, 870–871.

[33] X. Xie, C. L. Liotta, C. A. Eckert, Ind. Eng. Chem. Res.2004, 43, 7907.

[34] L. Hegedîs, T. M�th¦, Appl. Catal. A Gen. 2005, 296,209–215.

[35] L. Hegedîs, T. M�th¦, T. K�rp�ti, Appl. Catal. A Gen.2008, 349, 40–45.

[36] M. Chatterjee, H. Kawanami, M. Sato, T. Ishizaka, T.Yokoyama, T. Suzuki, Green Chem. 2010, 12, 87–93.

[37] Y. Li, Y. Gong, X. Xu, P. Zhang, H. Li, Y. Wang, Catal.Commun. 2012, 28, 9–12.

[38] Y. Yoshida, Y. Wang, S. Narisava, S. Fujita, R. Lia, M.Arai, Appl. Catal. A 2013, 456, 215–222.

[39] M. Vilches-Herrera, S. Werkmeister, K. Junge, A.Bçrner, M. Beller, Catal. Sci. Technol. 2014, 4, 629–632.

[40] C. S. Chin, B. Lee, Catal. Lett. 1992, 14, 135–140.[41] S. Lu, J. Wang, X. Cao, X. Li, H. Gu, Chem. Commun.

2014, 50, 3512–3515.[42] S. Laval, W. Dayoub, A. Favre-Reguillon, M. Berthod,

P. Demonchaux, G. Mignani, M. Lemaire, TetrahedronLett. 2009, 50, 7005–7007.

[43] K. Rajesh, B. Dudle, O. Blacque, H. Berke, Adv. Synth.Catal. 2011, 353, 1479–1484.

[44] I. Cabrita, A. C. Fernandes, Tetrahedron 2011, 67,8183–8186.

[45] J. Z. Saavedra, A. Resendez, A. Rovira, S. Eagon, D.Haddenham, B. Singaram, J. Org. Chem. 2012, 77, 221–228.

[46] C. N. Rao, S. Hoz, J. Org. Chem. 2012, 77, 4029–4034.[47] J. B. Branco, D. Ballivet-Tkatchenko, A. P. de Matos, J.

Phys. Chem. C 2007, 111, 15084–15088.[48] J. B. Branco, D. B-Tkatchenko, A. P. de Matos, J. Mol.

Catal. A: Chem. 2009, 307, 37–42.[49] R. K. Marella, K. S. Koppadi, Y. Jyothi, K. S. Rama R-

ao, D. R. Burri, New J. Chem. 2013, 37, 3229–3235.[50] M. Szostak, B. Sautier, M. Spain, D. J. Procter, Org.

Lett. 2014, 16, 1092–1095.[51] M. Nabid, Y. Bide, M. Niknezhad, ChemCatChem

2014, 6, 538–546.[52] S. Chakraborty, H. Berke, ACS Catal. 2014, 4, 2191–

2194.[53] C. Bornschein, S. Werkmeister, B. Wendt, H. Jiao, E.

Alberico, W. Baumann, H. Junge, K. Junge, M. Beller,Nat. Commun. 2014, doi:10.1038/ncomms5111.




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