Efficient hydrogenation of organic carbonates,carbamates and formates indicates alternativeroutes to methanol based on CO2 and COEkambaram Balaraman1, Chidambaram Gunanathan1, Jing Zhang1, Linda J. W. Shimon2

and David Milstein1*

Catalytic hydrogenation of organic carbonates, carbamates and formates is of significant interest both conceptually andpractically, because these compounds can be produced from CO2 and CO, and their mild hydrogenation can providealternative, mild approaches to the indirect hydrogenation of CO2 and CO to methanol, an important fuel and syntheticbuilding block. Here, we report for the first time catalytic hydrogenation of organic carbonates to alcohols, and carbamatesto alcohols and amines. Unprecedented homogeneously catalysed hydrogenation of organic formates to methanol has alsobeen accomplished. The reactions are efficiently catalysed by dearomatized PNN Ru(II) pincer complexes derived frompyridine- and bipyridine-based tridentate ligands. These atom-economical reactions proceed under neutral, homogeneousconditions, at mild temperatures and under mild hydrogen pressures, and can operate in the absence of solvent with nogeneration of waste, representing the ultimate ‘green’ reactions. A possible mechanism involves metal–ligand cooperationby aromatization–dearomatization of the heteroaromatic pincer core.

The hydrogenation of polar bonds, in particular organic carbonylgroups, has captured much attention during the past fourdecades1–3, mainly due to its synthetic significance as an envir-

onmentally benign approach to fundamental synthetic buildingblocks such as alcohols and amines. Much progress has beenmade in the hydrogenation of ketones and aldehydes and, morerecently, rare examples of the significantly more difficult hydrogen-ation of esters4,5 and amides6,7 have also been reported. However, thehydrogenation of organic carbonates and carbamates remains amajor challenge. Indeed, as far as we know, catalytic hydrogenationof these important families of compounds has never been reported,be it under heterogeneous or homogeneous catalysis. In fact, organiccarbonates have been used as solvents in catalytic hydrogenationreactions8. Moreover, the popular amine protecting groups, benzylcarbamates, undergo deprotection by heterogeneous hydrogenation,which involves cleavage of the benzyl–O bond, but with thecarbonyl group not being reduced9. In addition, hydrogenation ofcyclic N-acylcarbamates leads to cleavage of the C–N bondwithout affecting the carbamate group10.

Hydrogenation of carbonates and carbamates is of considerableinterest conceptually and practically, because these compounds canbe readily formed from CO2 or from CO, and their mildhydrogenation would effectively mean indirect hydrogenation of thelatter compounds to methanol. In addition, mild hydrogenation ofmethyl formate, which can be produced from CO2 or CO, is of greatinterest as an alternative route to the conversion of these gases tomethanol. Heterogeneously catalysed hydrogenation of methyl formateunder high pressure and temperature has been reported11,12, but weare unaware of reports of homogeneously catalysed hydrogenations.Attempts at homogeneous hydrogenations of formate esters resultedin decomposition to CO and alcohol, with no methanol formation13.

Methanol is industrially produced from syngas at high tempera-tures (250–300 8C) and high pressures (50–100 atm) using acopper-zinc-based oxide catalyst14,15. In contrast, the carbonylation

of methanol to methyl formate16,17 or oxidative carbonylation todimethyl carbonate18,19 occurs under relatively mild conditions,and their mild hydrogenation could provide a desirable route tomethanol (Fig. 1).

Production of methanol from CO2 by direct hydrogenationunder mild conditions is an attractive goal, but a practical catalyticprocess has not yet been developed20–22. On the other hand, efficienttransformation of CO2 to formic acid and its derivatives (forexample, methyl formate) is known and well investigated23–29.Heterogeneous hydrogenation of methyl formate to methanol inthe gas phase30–33 as well as the liquid phase using a semi batch

CO MeOH+

CO 2 MeOH+1/2 O2

–H2O

a

b

3 MeOH

CO2 + H2

2H22 MeOH

MeOH

CO2

3H2

2 MeOH+

CO2MeOH 3H2 2 MeOH

c

H OMe

O

MeO OMe

O

R NH2

R NH

OMe– R NH2

O

Figure 1 | Alternative routes to methanol based on methyl formate,

dimethyl carbonate and organo-carbamates. a, Synthesis of methyl formate

either from CO or CO2 followed by hydrogenation. b, Synthesis of dimethyl

carbonate either from CO or CO2 followed by unprecedented hydrogenation.

c, Synthesis of organo-carbamates from CO2 followed by

unprecedented hydrogenation.

1Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot, 76100, Israel, 2Department of Chemical Research Support, The WeizmannInstitute of Science, Rehovot, 76100, Israel. *e-mail: david.milstein@weizmann.ac.il

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reactor34 has been reported at elevated temperatures, with lowselectivity. However, this method suffers from side reactions suchas the formation of CO by-product from the decomposition ofmethyl formate, making it less attractive.

The synthesis of dimethyl carbonate from CO2 is well documen-ted35,36, but to the best of our knowledge the hydrogenation of organiccarbonates (such as dimethyl carbonate) to methanol remainsunknown25,37. Methods for the synthesis of methyl carbamatesfrom CO2, methanol and amines have also been reported36,38,39.Thus, catalytic hydrogenation of the organic carbonates, carbamatesand formates to methanol under mild conditions could provide anindirect method to obtain methanol from CO2 and from CO (Fig. 1).

We have developed several reactions catalysed by pincer complexesbased on pyridine4,40–46 and acridine backbones47,48, including thehydrogenation of esters4 catalysed by 1 and, very recently, selectivehydrogenation of amides7 to the corresponding alcohols and aminesby cleavage of the C–N bond under homogeneous conditions, cata-lysed by bipyridine-based pincer complex 2. These reactions arethought to involve a new mode of metal–ligand cooperation basedon ligand aromatization–dearomatization, which has also led to con-secutive water splitting promoted by complex 1 (ref. 49).

Here we report the first examples of catalytic hydrogenation oforganic carbonates to alcohols and organic carbamates to alcoholsand amines, and homogeneously catalysed hydrogenation of alkylformates to methanol and the corresponding alcohols. The reactionsare selective, proceed efficiently under mild, neutral conditions, havehigh turnover numbers, and generate no waste. In addition, theyalso proceed very efficiently under solvent-free conditions. Thesenew reactions provide interesting alternatives for the mild hydro-genation of CO2 and CO to methanol, which is a timely topic inthe context of the ‘methanol economy’50. Some key mechanisticinsight is also provided.

Results and discussionCatalytic hydrogenation of organic carbonates. Complexes 1 and 2were investigated as catalysts for the catalytic hydrogenation oforganic carbonates to alcohols. Dimethyl carbonate was selected asa benchmark substrate for the hydrogenation reactions. Thus,treatment of dimethyl carbonate (25 mmol) with dihydrogen(40 atm) at 145 8C for 3.5 h with a catalytic amount of 1(0.01 mmol), using 1,4-dioxane as solvent, resulted in completeconversion with selective formation of methanol, with a turnovernumber (TON) of 2,500 (Table 1, entry 1). With 60 atm of H2,quantitative formation of methanol was observed even after1 h (TOF¼ 2,500 h21), with corresponding consumption ofdihydrogen (Table 1, entry 2). Using catalyst 2 (0.1 mol%), reaction

of dimethyl carbonate with H2 (10 atm) at 110 8C intetrahydrofuran (THF) for 48 h yielded 96% of methanol (Table 1,entry 3). It is quite remarkable that this novel hydrogenationreaction can proceed under such mild pressure (10 atm) and withhigh TON (960). Even higher TONs (4,400) were obtained usingcomplex 2 as a catalyst with 50 atm of dihydrogen (Table 1, entry 4).Remarkably, the hydrogenation of dimethyl carbonate proceedssmoothly under solvent-free conditions with catalyst 2. Thus,performing the reaction at 100 8C resulted in 89% conversion ofdimethyl carbonate to methanol after 2 h, and quantitativeconversion was observed after 8 h (Table 1, entries 5 and 6). Thisrepresents an ultimate green transformation—no solvent, no waste,complete selectivity, quantitative yield and under very mild conditions.

Complex 2 also efficiently catalyses the hydrogenation of otherorganic carbonates to the corresponding alcohols. For example,diethyl carbonate was selectively hydrogenated to ethanol (91%)and methanol (89%) after 8 h in almost complete conversion(93%) and with a good TON (910, based on ethanol). The

N

Ru

P

N

tBu

CO

tBuH N

Ru

P

N

tBu

CO

tBuH

N

Ru

P

N

tBu

CO

tBuH

H

N

Ru

P

N

tBu

CO

tBuH

Cl

21

43

Table 1 | Hydrogenation of dimethyl carbonate to methanol.

3H2 3 MeOH+1 or 2

MeO

O

OMe Δ

Entry Cat. Solvent pH2 Time(h)

Conv.(%)*

Yield(%)*

TON

1† 1 1,4-dioxane 40 3.5 .99 .99 2,5002† 1 1,4-dioxane 60 1 .99 .99 2,5003‡ 2 THF 10 48 96 96 9604§ 2 THF 50 14 89 88 4,4005} 2 Neat 10 2 89 89 8906} 2 Neat 10 8 .99 .99 .990

*Yields of methanol and conversion of dimethyl carbonate were determined by gas chromatography(GC) using m-xylene as an internal standard. †Complex 1 (0.01 mmol), dimethyl carbonate(25 mmol) and 1,4-dioxane (20 ml) were heated in a Parr apparatus at 145 8C. ‡Complex 2(0.01 mol) and dimethyl carbonate (10 mmol) were heated in a Fischer-Porter tube at 110 8C.§Complex 2 (0.005 mmol), dimethyl carbonate (25 mmol) and dry THF (5 ml) were heated in anautoclave at 110 8C. }Complex 2 (0.01 mmol) and dimethyl carbonate (10 mmol) were heated at100 8C.

Table 2 | Hydrogenation of methyl carbamates to methanoland amines.

3H2 2 MeOH+2

NH

O

OMeR

NH2– R

Δ

Entry Carbamate Amine Alcohol Yield*

1

NH

O

OMe NH2

MeOH 97

2

NH

O

OMe

MeO

NH2

MeO

MeOH 98

3Pentyl

NH

O

OMeNH2

MeOH 94

Complex 2 (0.01 mmol), carbamate (1 mmol), H2 (10 atm) and dry THF (2 ml) were heated in aFischer-Porter tube at 110 8C (bath temperature). *Yields of product (based on MeOH) wereanalysed by GC using m-xylene as an internal standard.

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reaction was performed under solvent-free conditions under mildpressure ( pH2¼ 10 atm) and low temperature (100 8C). In noneof these hydrogenations did we observe any formation ofalkyl formates.

Catalytic hydrogenation of carbamates. In still anotherunprecedented reaction, complex 2 catalyses the hydrogenation ofmethyl carbamates to methanol and the corresponding amines.Thus, heating a solution of methyl N-benzyl carbamate(1.0 mmol) and dihydrogen (10 atm) with a catalytic amount ofcomplex 2 (0.01 mmol) at 110 8C in THF for 48 h selectivelyyielded methanol and benzylamine in quantitative yields. Otherexamples are listed in Table 2.

Remarkably, benzyl carbamates were also selectively hydrogen-ated to yield methanol, the corresponding amines and benzylalcohol, without cleavage of the benzyl–O bond. Thus, upon treat-ment of benzyl morpholine-4-carboxylate with H2 (10 atm) at110 8C in dry THF for 52 h with a catalytic amount of 2(1 mol%), 88% of benzyl alcohol, 87% of morpholine and 81% ofmethanol were obtained (Fig. 2a). It is important to note that inthe hydrogenolysis of benzyl carbamates, used for deprotection ofcarbamate-N functional groups catalysed by Pd/C, the deprotectedamine and free CO2 (via a carbamic acid intermediate) are formed9.The reaction occurs by cleavage of the benzyl–O bond, but the car-bonyl group is not reduced, unlike the benzyl carbamate hydrogen-ation reported here (Fig. 2b).

Homogeneous hydrogenation of alkyl formates. Finally, weexamined the possibility of homogeneous hydrogenation of alkylformates to methanol and the corresponding alcohols using

complexes 1–4 as catalysts. Reaction of methyl formate anddihydrogen (7 atm) catalysed by 1 (0.1 mol%) at 145 8C in 1,4-dioxane yielded 71% of methanol after 30 h (Table 3, entry 1).Performing the reaction under 9 atm of H2 resulted in completeconversion of methyl formate to methanol after 36 h with completeselectivity (Table 3, entry 2). Using a lower temperature, complex1 (0.01 mmol) was heated with methyl formate (15 mmol) anddihydrogen (10 atm) at 110 8C in THF for 48 h to yield 77% ofmethanol (Table 3, entry 3). With catalyst 2, under the sameconditions (methyl formate/2¼ 1,500/1, 10 atm of H2, 110 8C inTHF for 48 h), 96% conversion of methyl formate into methanol wasobserved (Table 3, entry 4). Importantly, GC analysis of the reactionmixtures indicated the absence of CO, which is a problematicby-product in heterogeneously catalysed hydrogenation of methylformate35–39. Using 50 atm of H2, even higher TONs (Table 3, entries5 and 6) were achieved (up to 4,700) using complex 2. Notably, theair-stable hydrido chloride complex7 4 in the presence of oneequivalent of base (relative to Ru) also efficiently catalysed thehydrogenation of methyl formate; in this reaction the actual catalyst2 is generated in situ by deprotonation of 4. Thus, upon heating aTHF solution of complex 4 (0.01 mmol) with KOtBu (0.01 mmol)and methyl formate (15 mmol) at 110 8C under H2 (10 atm) for48 h, methanol was formed in 91% yield (Table 3, entry 8). Noreaction took place in the absence of base (Table 3, entry 9).Importantly, hydrogenation of methyl formate is efficiently catalysedby 2 under solvent-free conditions, as in the case of dimethylcarbonate. Thus, heating a solution of methyl formate (10 mmol)and a catalytic amount of 2 (0.01 mmol) at 80 8C under H2 (10 atm)resulted in quantitative conversion of methyl formate selectivelyto methanol after 8 h, with the corresponding consumption ofdihydrogen (Table 3, entry 10). Like in the case of dimethylcarbonate, this is an ultimate green transformation—no solvent, nowaste, complete selectivity, quantitative yield, and under very mildconditions. Under the same solvent-free conditions, catalyst 1 is lesseffective and affords only �16% conversion of methyl formate.

Hydrogenation of other formate esters also proceeds efficiently.Thus, reaction of ethyl formate with H2 (10 atm) at 110 8C inTHF for 48 h catalysed by 2 (formate/2¼ 1,500/1) resulted in92% of ethanol and 91% of methanol without formation of CO orethyl acetate. In the same way, hydrogenation of n-butyl formatecatalysed by 2 resulted in 86% conversion and selectively yieldedmethanol (82%) and n-butanol (84%).

Mechanistic studies of the hydrogenation of organic carbonatesand formates. The mechanism of these unusual hydrogenationreactions is of interest. As we reported, the trans-dihydride 3 is

Table 3 | Homogeneously catalysed hydrogenation of methyl formate to methanol.

2H2 2 MeOH+Cat.

H

O

OMe Δ

Entry Cat. Solvent Temp. (88888C) pH2 Time (h) Conv. (%)* Yield (%)* TON

1 1 1,4-dioxane 145 7 30 72 71 7102 1 1,4-dioxane 145 9 36 .99 �99 �9903 1 THF 110 10 48 78 77 1,1554 2 THF 110 10 48 96 96 1,4405† 2 THF 110 50 8 87 85 4,2506† 2 THF 110 50 14 94 94 4,7007 3 THF 110 10 48 84 81 1,2158‡ 4 THF 110 10 48 93 91 1,3659 4 THF 110 10 48 – – –10§ 2 Neat 80 10 8 �99 98 980

Complexes 1, 2, 3 or 4 (0.01 mmol), methyl formate (10 mmol for entries 1–2; 15 mmol for entries 3–4, 7–9), H2 and dry solvent (2 ml) were heated in a Fischer-Porter tube at the specified (oil bath) temperature.*Yields of methanol and conversion of methyl formate were analysed by GC using m-xylene as an internal standard. †Complex 2 (0.005 mmol), methyl formate (25 mmol), and THF (5 ml) were heated under H2

pressure in an autoclave. ‡One equiv (relative to Ru) of KOtBu was used. §Complex 2 (0.01 mmol) and methyl formate (10 mmol) were used neat.

+

O

O

NPh

O

Pd/C

H2 NH

O

+ CO2

3H2

Ph CH2OHCat. 2

NH

O

+ MeOH+

a

b

Ph CH3

Figure 2 | Hydrogenation of a benzyl carbamate. a, Unprecedented

hydrogenation to methanol, amine and benzyl alcohol catalysed by 2.

b, A common amine deprotection by heterogeneous hydrogenation of benzyl

carbamate with cleavage of the benzyl–O bond and liberation of free CO2.

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formed by treatment of the dearomatized 1 with dihydrogen4. Asingle-crystal X-ray diffraction study of 3 (Fig. 3) reveals adistorted octahedral geometry around the ruthenium centre, withthe CO ligand coordinated trans to the pyridyl nitrogen atom.Complex 3 also catalyses the hydrogenation of methyl formate tomethanol (Table 3, entry 7).

Reaction of the trans-dihydride 3 with dimethyl carbonate(�2.5 equiv.) in toluene-d8 in a sealed NMR tube at 50 8C resultedin the formation of free methyl formate and methanol in 5 min, asobserved by 1H NMR, together with the fully characterized, newdearomatized dicarbonyl complex 5 (Fig. 4a and SupplementaryInformation). Presumably, after reaction with one equivalent of

dimethyl carbonate to deliver methyl formate, the in situ generatedcomplex 1 (in the absence of dihydrogen) reacts further with excessof dimethyl carbonate, leading to 5 (see Supplementary Informationfor reaction of 1 with dimethyl carbonate) by the decomposition ofdimethyl carbonate to methanol, CO and H2 (note that no CO wasobserved in the catalytic hydrogenation reactions, because 1 reactswith H2 to form 3).

Analogous stepwise hydrogenation was also observed for the case ofmethyl formate. Upon reaction of methyl formate (�2.5 equiv.) with 3at room temperature, formation of methanol and a complex tentativelyassigned as a formaldehyde Ru(II) intermediate 6 was observed after10 min (Fig. 4b)51. The aldehyde proton of 6 appears as a singlet at9.21 ppm (�0.5 ppm downfield relative to free formaldehyde, whichappears at 8.73 ppm in toluene-d8). After prolonged standing atroom temperature (�6 h), the signal of 6 slowly diminished, togetherwith the formation of the fully characterized, methoxy Ru(II) species 7,which was independently prepared by the addition of methanol tocomplex 1 (see Supplementary Information).

On the basis of the above results and the metal–ligandcooperation by aromatization–dearomatization prevalent in thechemistry of pincer complexes 1 (ref. 44) and 2 (ref. 7), wepropose a possible mechanism for the hydrogenation of dimethylcarbonate and methyl formate catalysed by 1 (Fig. 5), althoughmore studies are needed for mechanistic interpretation. Initially,dihydrogen addition by metal–ligand cooperation to complex 1results in aromatization, to form the coordinatively saturated,trans-dihydride complex 3, as previously observed4. Subsequenthydride transfer to the carbonyl group of the carbonate ligandcan lead to intermediate A. This process may involve directhydride attack on the ester or alternatively dissociation of thepyridyl arm to provide a site for dimethyl carbonate coordination.Deprotonation of the benzylic arm by the adjacent methoxygroup can result in liberation of methanol and the formation of adearomatized intermediate B, bearing a coordinated methylformate. Dihydrogen addition to B (which may also involveamine arm opening), followed by hydride transfer to methylformate, can generate a intermediate C. Deprotonation of thebenzylic arm by the methoxy group can generate the productmethanol and a formaldehyde intermediate 6, which undergoeshydrogenation to the characterized methoxy intermediate 7.Methanol liberation from complex 7 regenerates catalyst 1.

Similarly, in the case of hydrogenation of methyl formate, reac-tion with the dihydride 3 can give intermediate C. Deprotonation

O1C1RU1

P3

1HA

N2

N11HB

Figure 3 | X-ray structure of complex 3 (50% probability level). Hydrogen

atoms (except hydrides) are omitted for clarity. Selected bond distances (Å)

and angles (deg): Ru1–N1 2.101 (3), Ru1–N2 2.251 (3), Ru1–P3 2.252 (1),

Ru1–C1 1.821 (4), H1A–Ru1 1.71 (4) Å, (H1B–Ru1 was not refined). N1–Ru1–C1

175.0 (2), N1–Ru1–P3 82.6 (1), N1–Ru1–N2 78.0 (1), N2–Ru1–P3 160.6 (1),

N2–Ru1–C1 104.8 (2), C1–Ru1–P3 94.6 (1).

N

Ru

P

N

tBu

CO

tBuH

H

3

2

a

MeO OMe

O

Δ, –H2, –COH OMe

O

+ 2MeOH +

N

Ru

P

N

tBu

CO

tBuH

CO

5

N

Ru

P

N

tBu

CO

tBuH

H

3

b

H OMe

O

6

N

Ru

P

N

tBu

CO

tBuO

HH

H

+ MeOH

N

Ru

P

N

tBu

CO

tBuO

H

CH3

7

1MeOH

Figure 4 | Reactivities of the saturated Ru(II)–trans-dihydride complex 3, suggesting its intermediacy in the catalytic hydrogenation mechanism. a,

Reaction with dimethyl carbonate leads to methyl formate, methanol and complex 5. b, Reaction of complex 3 with methyl formate resulted in methanol,

formaldehyde intermediate 6 and methoxy intermediate 7.

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of the benzylic arm by the methoxy group (as with intermediate B inthe case of dimethyl carbonate) leads to methanol and intermediates6 and 7, as indicated experimentally (Fig. 4b). Further mechanisticstudies are in progress.

In conclusion, for the first time, selective hydrogenations ofthe CO2 (and CO)-derived organic carbonates, formates and carba-mates to methanol were demonstrated using soluble, well-definedmetal complexes as catalysts. The reactions, catalysed by PNNcomplexes 1–3, proceed efficiently and selectively under mild,neutral conditions using mild hydrogen pressure, without thegeneration of any waste or by-products (such as CO) and withhigh TONs. Moreover, the reactions proceed very well also inabsence of solvent, as demonstrated for the cases of dimethyl car-bonate and methyl formate, representing ultimate ‘green’ reactions.A postulated mechanism involving metal–ligand cooperation issupported by stoichiometric reactions of dimethyl carbonate andmethyl formate with dihydride complex 3. The high efficiencyand selectivity of these new, environmentally benign reactionsprovide mild, indirect routes to methanol from CO2 and COvia hydrogenation of dimethyl carbonate, methyl formate andmethyl carbamates.

Received 21 February 2011; accepted 10 June 2011;published online 22 July 2011

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N

Ru

PtBu2

NEt2

CO

H

H

3

N

Ru

PtBu2

NEt2

CO

H

1

N

Ru

PtBu2

NEt2

CO

O

H

Me

N

Ru

PtBu2

NEt2

CO

O

H

HH

N

Ru

PtBu2

NEt2

CO

O

H

HH

OMeN

Ru

PtBu2

NEt2

CO

O

H

HOMe

N

Ru

PtBu2

NEt2

CO

O

H

HH

OMe

OMe

H2

MeOHH2

H2

MeOH

MeO

O

OMe

MeOH

7

A 6

B C

Figure 5 | Postulated mechanism for novel, homogeneous hydrogenation of dimethyl carbonate and methyl formate to methanol catalysed by complex 1.

The mechanism involves metal–ligand cooperation by aromatization–dearomatization of the heteroaromatic pincer ligand and hydride transfer to the

carbonyl group.

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AcknowledgementsThis research was supported by the European Research Council under the FP7 framework(ERC no. 246837), by the Israel Science Foundation, and by the MINERVA Foundation.D.M. is the Israel Matz Professorial Chair of Organic Chemistry.

Author contributionsE.B. carried out catalytic experiments, mechanistic studies and contributed to writing themanuscript. C.G. carried out catalytic experiments and contributed to writing themanuscript. J.Z. prepared and crystallized complex 3. L.J.W.S. conducted the X-raystructural study of complex 3. D.M. carried out the design and direction of the projectand contributed to writing the manuscript.

Additional informationThe authors declare no competing financial interests. Supplementary informationaccompanies this paper on www.nature.com/naturechemistry, including synthesis andX-ray structural determination of 3, mechanistic stoichiometric reactions, generalprocedures for the catalytic hydrogenation reactions, and cif file for 3 (CCDC #826775)and chemical compound information accompanies this paper at www.nature.com/naturechemistry. Reprints and permission information is available online at http://www.nature.com/reprints. Correspondence and requests for materials should be addressed to D.M.

ARTICLES NATURE CHEMISTRY DOI: 10.1038/NCHEM.1089

NATURE CHEMISTRY | VOL 3 | AUGUST 2011 | www.nature.com/naturechemistry614

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