Solvent-Induced Reduction of Palladium-Aryls, a PotentialInterference in Pd CatalysisJesus A. Molina de la Torre, Pablo Espinet, and Ana C. Albeniz*

IU CINQUIMA/Química Inorganica, Universidad de Valladolid, 47071-Valladolid, Spain

*S Supporting Information

ABSTRACT: The decomposition of the Pd-aryl complex(NBu4)2[Pd2(μ-Br)2Br2(C6F5)2] (1) to the reduction productC6F5H was checked in different solvents and conditions. 1 is notstable in N-alkyl amides (DMF, NMP, DMA), cyclohexanone,and diethers (1,4-dioxane, DME) at high temperatures (above 80°C). Other solvents such as nitriles, THF, water, or toluene aresafe, and no significant decomposition occurs. The solvent is thesource of hydrogen, and the decomposition mechanisms havebeen identified by analyzing the reaction products coming fromthe solvent. β-H elimination involving the methyl group in a N-coordinated amide is the predominant pathway for amides. An O-coordinated diether undergoes β-H elimination and subsequentdeprotonation of the resulting oxonium salt to give an enol ether. A palladium enolate from cyclohexanone leads tocyclohexenone, a reaction favored by the presence of a base. Oxygen strongly increases the extent of decomposition, and wepropose this occurs by reoxidation of the Pd(0) species formed in the process and regeneration of active Pd(II) complexes.

■ INTRODUCTION

Palladium-catalyzed reactions are well developed, and a widevariety of processes, catalysts, and reaction conditions areavailable.1 Among the factors that have to be chosen by thechemical practitioner for a specific target process, the solvent isone of them. It is not rare that the adequacy of familiar solvents,which have shown to be appropriate in many similar reactions,is taken for granted and their potential risks are overlooked.This is good enough when, in catalysis, the reaction is fast andthe percentage of undesired byproducts is acceptably small.However, in processes requiring long reaction times the picturecan seriously change, and some of those solvents may play anundesired role and become reagents responsible for secondaryreactions that reduce the selectivity of the process.Many reports in the literature mention the appearance of

byproducts, often reduction products when organic halides areused, in Pd-catalyzed transformations. Sometimes the solvent isdeemed responsible, and plausible pathways are proposed forthese side reactions.2−5 However, few attempts have been madeto identify the decomposition products from the solvent thatcould substantiate a proposed pathway. Also, it needs to bekept in mind that some of the reagents used in a couplingprocess can also be a source of hydrogen and give reductionproducts (for example, Pd−H species generated in each Heckcatalytic cycle or a Bu group transferred to palladium fromSnBu3R in Stille couplings that undergoes β-H elimination).Thus, details on which solvents are safe to carry out the chosenreaction or more risky and thus may be a potential source ofundesired reduction byproducts are missing.We report here a study that shows the ability of different

solvents to produce the decomposition of palladium aryl

complexes to arenes and analyzes the solvent decompositionproducts and the decomposition mechanisms. The influence ofcommon additives in C−C coupling reactions such as bases isaddressed. Also, the effect of the presence of oxygen, which isbecoming important in the oxidative versions of the C−Ccoupling reactions that use alkanes as substrates and are soughtas greener alternatives,6 is considered.

■ RESULTS AND DISCUSSION

We have used (NBu4)2[Pd2(μ-Br)2Br2(C6F5)2] (1) as our Pd-aryl model compound in this study. This is a monoaryl-palladium complex devoid of strong coordinating ligands, whichis stable at room temperature both in the solid state and insolution, so it can be easily prepared and stored. The presenceof a fluoroaryl moiety allows the monitoring of the reactions by19F NMR and also slows the classical reactivity of aryl-Pdcomplexes, reproducing the desired scenario of slow catalysis.7

Complex 1 has been used as a catalyst precursor in the Heckreaction of fluoroaryl derivatives to give alkenes withfluorinated substituents.8,9 Pd-C6F5 complexes related to 1are the expected intermediates in the former reactions as well asother processes such as oxidative Heck reactions ofpentafluorobenzene10 or Stille cross-coupling reactions ofhalopentafluorobenzenes.11

Depending on the polarity, the coordination ability of thesolvent, and the concentration range, a solution of 1 in aspecific solvent can be a mixture of several species, i.e.,(NBu4)2[Pd2(μ-Br)2Br2(C6F5)2] (1) (cis and trans isomers),

Received: July 19, 2013

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(NBu4)[PdBr2(C6F5)L], [PdBr(C6F5)L2] (L = solvent), andeven (NBu4)2[PdBr3(C6F5)], if the concentration of Br−

increases upon decomposition of 1. We have not studiedthese equilibria in detail here, but some studies can be foundelsewhere.8 All these compounds are characterized by 19F NMRchemical shifts for the Fortho in the range −112 to −120 ppm(C6F5-Pd), quite different from C6F5 bound to H or a carbonmoiety (around −140 ppm).Table 1 collects the amount of C6F5H obtained when 1 was

heated at 100 °C in different solvents (eq 1), in the presence or

absence of oxygen and a strong base (aqueous NaOH, mol ratioPd:base = 1:1). The formation of C6F5H was quantified by 19FNMR in the crude mixture, and it is the only organic productderived from the Pd-C6F5 moiety.12

Complex 1 is soluble in most solvents, but only sparinglysoluble in water, toluene, and 1,4-dioxane. Thus, after theheating time in the latter solvents the mixture was dissolved (orextracted) by addition of a suitable solvent (usually CH2Cl2 oracetone) and the percentage of C6F5H was quantified by 19FNMR. After the heating period in some of the solvents used, wecould observe the formation of additional organometalliccomplexes; they result form the rearrangement of aryl groupsin 1 to give complexes bearing a “Pd(C6F5)2” moiety.13

Solvents such as toluene, THF, nitriles, or water are safe, andno or very little decomposition to C6F5H was observed ineither the absence or presence of oxygen or when a strong basewas added (entries 5−7, 10, and 11, Table 1). The same isobserved for a mixture of THF/H2O or MeCN/H2O (1:1 involume), where complex 1 is soluble (entries 12 and 13, Table1). On the other hand, depending on the reaction conditions,amides (dimethylformamide, DMF; dimethylacetamide, DMA;N-methylpyrrolidone, NMP), diethers (1,4-dioxane; 1,2-dimethoxyethane, DME), and cyclohexanone produce signifi-cant amounts of the reduction product C6F5H. Oxygen andsodium hydroxide have different effects on the stability of 1 in

these solvents, so each type will be discussed separately.Alcohols have not been tested since they have proved to beexcellent reducing agents for palladium complexes and themechanism of this reactions is well known.14−16

Amides. Complex 1 is stable in amides in the absence ofbase or oxygen at 100 °C for 2 h. No decomposition wasobserved in DMF or DMA, and a very small amount of C6F5Hwas observed in NMP (entries 1A−3A, Table 1). Longerreaction times under these conditions lead eventually to anoticeable but slight decomposition. For instance, heating 1 at100 °C in deoxygenated DMF for 72 h produces 2% C6F5H.The amount of water does not influence the decomposition,thus 1.5% C6F5H was observed when 1 was kept at 100 °Cunder nitrogen in a NMP:water = 10:1 mixture in volume (cf.1.3% C6F5H without added water, entry 3A, Table 1). Thepresence of oxygen leads to a remarkable decrease in thestability of 1, and the percentage of decomposition follows thetrend DMF > NMP. The presence of base also decreases thestability of 1 but has a smaller influence. Although a slightincrease in the amount of C6F5H is observed for DMA, 1 isquite stable in this solvent except when subjected to longheating periods (entry 2F, Table 1).Along with C6F5H, only two products derived from DMF,

methylformamide (2a) and methylformimide (3a), weredetected by 1H NMR and GC-MS. These products were notobserved when DMF was heated without 1 in the presence ofoxygen and base for 48 h. Thus, we propose the reactionpathway depicted in Scheme 1.17 The detection of methyl-formamide (2a) indicates that the methyl group of the amide isinvolved in a β-H elimination reaction to give an iminiun saltand a palladium hydride that leads to C6F5H by reductiveelimination.18 The iminium salt is easily hydrolyzed to 2a andformaldehyde. In the presence of oxygen, formaldehyde isoxidized to formic acid, which leads, by reaction with 2a, to theimide 3a. The latter reactions have been tested independently(see Supporting Information).19

The same reactivity pattern is observed for NMP and DMA.Methylacetamide (2b) and the imide 3b were detected, alongwith C6F5H, when 1 was decomposed in DMA under stringentconditions (entry 2F, Table 1). Formimide 4 was detected inthe decomposition reactions of 1 in NMP (Scheme 2). In this

Table 1. Decomposition Data of Complex 1 to C6F5H (%) in Different Solvents and Conditionsa

A B C D E F

entry solvent N2 air O2 N2, NaOH air, NaOH O2, NaOH, 72 h

1 DMF 0 22 88 12.4 37.5 97.32 DMA 0 0.5 1.1 2.7 4.2 213 NMP 1.3 11.5 42.8 5.7 11.8 794 cyclohexanone 3.5 25.5 44.8 62.5 26.2 955b H2O 0 0 0 0 06c toluene 0 0 0 0 07 THF 0 0 0 0.7 0.68c 1,4-dioxane 0 5.4 23 0.5 0.59 DME 0.1 0.4 22 0.7 210 MeCN 0 0 0 2.4 2.411 i-PrCN 0.2 0.8 0.5 0.6 1.312d THF/H2O 1.813d MeCN/H2O 0

aAll the experiments were carried out at 100 °C for 2 h, except those collected in the last column for some of the solvents (72 h). Mol percentages ofC6F5H are given. b1 was insoluble; the mixture was extracted with CH2Cl2 after the reaction time and checked by NMR. c1 was sparingly soluble;CH2Cl2 (toluene) or acetone (1,4-dioxane) was added to the mixture after the reaction time to obtain a clear solution to be checked by NMR.dSolvent:H2O ratio 1:1 v/v.

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case we could not detect pyrrolidone, presumably formed in thedecomposition process and playing the same role as 2 inScheme 1.

The amount of compounds 2−4 is generally higher that theamount of C6F5H produced in the decomposition. Whenoxygen is present, the formation of 2+3 or 4 is clearlycatalytic.20 It is likely that oxygen, besides having an influencein the nature of the final products formed (imides), isreoxidizing the Pd(0) formed in the reaction to Pd(II).These new Pd(II) complexes can coordinate the amide,undergo β-H elimination, and generate new Pd−H species.We have shown before that hydride can be transferred betweentwo palladium atoms.21 Thus, this is a plausible additionalpathway for the formation of “PdH(C6F5)” species, which couldexplain the effect of oxygen in the extensive decomposition of 1to C6F5H in DMF or NMP (Scheme 3). In an independentexperiment we observed that 2a and 3a were formed by heating(NBu4)2[Pd2(μ-Br)2Br4] in DMF under oxygen for 2 h (2turnovers per Pd).Complex 1 decomposes in the amides tested following the

trend DMF > NMP > DMA, which seems consistent with the

coordination ability of these solvents (see first step in Scheme1). This point was assessed by measuring the equilibriumconstant for the bridge-splitting reaction in eq 2. The dinuclear

complex (NBu4)2[Pd2(μ-Br)2(C6F5)4] (5) shows equivalentpentafluorophenyl rings which become nonequivalent in themonomeric species 6; this allows to measure easily the extent ofcoordination, K = [6]/[5]1/2. As expected, KDMF, 0.097 ±0.002, > KNMP, 0.0748 ± 0.0018, > KDMA, 0.0443 ± 0.0011. Theimportance of the coordination of the solvent is also shown inthe behavior of [PdBr(C6F5)(AsPh3)2] in DMF under air for 2h at 100 °C; the complex is stable and no C6F5H was observed(cf. 22% for 1 in the same conditions, entry 1B, Table 1).AsPh3, not a particularly strong ligand for Pd(II),22 is a betterligand than DMF, and the coordination of the latter ishampered. Thus, the undesired reaction with the solvent isespecially probable for palladium complexes with easilyavailable coordination sites, as it is the case of the so-called“ligandless catalysts”, where the role of the solvent as a ligand isalmost impossible to avoid.All these solvents can be safely used below or at 50 °C, and 1

does not decompose in DMF under oxygen at that temper-ature. However the decomposition is patent at 80 °C (24%C6F5H was formed in 2 h) and 100 °C (88% in 2 h, entry 1C,Table 1).None of these decomposition reactions seem to follow a

radical mechanism. Thus, no significant difference in thedecomposition of complex 1 was observed when it was heatedin NMP under N2 for 2 h in the dark (1.7% C6F5H) or underUV irradiation (λ = 352 nm, 2.2% C6F5H).

23

The presence of base has less influence in the decompositionof 1 than oxygen. The addition of NaOH(aq) increases theamount of C6F5H formed, slightly for DMA and NMP and to alarger degree for DMF. It is clear that some equilibria inScheme 1 should be favored by a base (i.e., hydrolysis of theiminium salt to give 2). Nonetheless the higher influenceobserved for DMF suggests that some other reaction, ahydrolysis of the amide for example, could occur. The use ofDMF as reagent, as well as its reactivity toward transition metalcomplexes, has been reviewed.24 It has been shown that DMF isa source of CO25 and also of hydrogen to give reductionproducts. In the case of palladium, the proposed pathway toexplain the behavior of DMF as hydrogen source involves itshydrolysis to give NHMe2, which coordinates to palladium andthen undergoes β-H elimination.26 However, we could notdetect dimethylamine or methylamine (a product eventuallyformed after β-H elimination) in any of our experiments withDMF. We heated 1 at 100 °C in a mixture of i-PrCN as solvent,NaOH(aq), and NHMe2 for 2 h (molar ratio Pd:NHMe2 =1:2) in order to quantify the maximum percentage of C6F5Hthat could be accounted for via NHMe2; the amount of C6F5Hfound was 9.2% under nitrogen and 13.4% under an oxygenatmosphere. In the absence of NaOH no decomposition wasobserved. These results point to a β-H elimination in apalladium amido complex as studied in detail by Hartwig et al.27

If some hydrolysis of the amide is taking place in basic media,this is not the main source of C6F5H.

Scheme 1. Decomposition of 1 in DMF and DMA

Scheme 2. Decomposition of 1 in NMP

Scheme 3. Reaction with the Solvent of Reoxidized Pd(II)Species and Hydride Transfer

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It is possible to devise reaction pathways where the formylhydrogen of DMF could play a role in the generation of a Pd−H moiety. In fact, formiates have been used as reducing agentsin many metal-catalyzed reactions including palladium.14,28 Inorder to check the involvement of the formyl group in thedecomposition of 1, we examined the decomposition of 1 inprotic DMF, D(CO)N(CD3)2, or D(CO)N(CH3)2 in thepresence of oxygen. The reaction in DMF-D7 (99.5% D) gaveC6F5D as the major product (ratio C6F5H:C6F5D = 1:4.3,Figure 1),29 whereas the reaction in DMF-D1 led mainly to

protic C6F5H (ratio C6F5H:C6F5D = 8:1). A strong kineticisotope effect was observed, and the reaction in DMF-D7 wasmuch slower (Figure 2). The residual protic solvent (0.5%) and

the remarkable rate differences observed when comparing theprotic and deuterated DMF account for the observation ofC6F5H in the experiment with DMF-D7 (Figures 1 and 2).Thus, β-H elimination involving the methyl groups, as shown inScheme 1, is the predominant pathway.Cyclohexanone. Cyclohexanone was used as a model for

ketones with β-hydrogens, and it was chosen for its high boilingpoint and the a priori more simple mixture of decompositionproducts. The results collected in Table 1, entry 4, indicate thatcyclohexanone is a potential reducing solvent. The presence ofbase strongly increases the amount of C6F5H (cf. experimentsunder nitrogen, entries 4A and 4D, Table 1), which points tothe formation of a palladium enolate that undergoes a

subsequent β-H elimination, as shown in Scheme 4. It isclear that this process can occur for any ketone with β-H atoms,

a reaction previously reported30 and efficiently used by Stahl etal. and others in the Pd-catalyzed formation of α,β-enones fromsaturated ketones.31 The process can occur again on cyclo-hexenone (7) to give cyclohexadienone and eventually phenol(8), as shown in Scheme 4.32 We have detected bothcyclohexenone and phenol, and their formation is also catalytic(32 turnovers observed for entry 4F, Table 1). The effect ofoxygen is similar to the one discussed before for amides, and itaccounts for the reoxidation of Pd(0) to Pd(II). Forcomparison, we carried out the reactions with acetone, whichcan form a palladium enolate, but β-H elimination in thisspecies is not possible. No C6F5H was detected in any of theconditions collected in Table 1 (columns A−E), indicating thatreduction is only to be expected for ketones with hydrogens ina β position.It is noteworthy that NMP could also generate a Pd hydride

by this enolate mechanism; the product, after β-H elimination,would be 1-methyl-3-pyrrolin-2-one. Since this product was notdetected in our reactions with NMP, the β-H elimination fromthe N-Me unit is dominant in methyl amides.

Diethers. Complex 1 is quite stable in 1,4-dioxane or DMEat 100 °C, provided oxygen is excluded. When theconcentration of oxygen increases, significant amounts ofC6F5H are detected. Dioxene (9) and the diformate 10 weredetected in the mixture when dioxane is used; hence wepropose the decomposition pathway depicted in Scheme 5. APd-H moiety is generated by β-H elimination on a coordinateddioxane. The generated oxonium salt deprotonates very easilyand leads to 9. This route has been proposed to explain somereduction products observed in a Pd-catalyzed cyclizationreaction, but dioxene was not detected.4

The oxidation of dioxene by oxygen via a dioxetaneintermediate to give dicarbonyl derivatives analogous to 10has been reported before.33 10 shows a characteristic HC(O)Osignal at 8 ppm in 1H NMR and a MS with a characteristicfragmentation pattern, which was compared with an authenticsample. The oxidation of 9 to 10 in 1,4-dioxane as solvent waschecked independently: it occurs to a small extent in theabsence of a palladium complex, but we observed that theaddition of [PdCl2(NCMe)2] increases the amount of 10.

Figure 1. 19F NMR of a mixture of C6F5H and C6F5D (Fortho region),showing the isotopic shift and different multiplicity.

Figure 2. Formation of C6F5X (X = H, D) in the reaction of 1 at 100°C under oxygen in DMF (upper line) and DMF-D7 (middle + lowerlines).

Scheme 4. Decomposition of 1 in Cyclohexanone andProducts Derived from It

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Thus, it is possible that palladium activates oxygen toward thisreaction, probably through the involvement of a peroxocomplex upon reaction of O2 with Pd(0).34,35

The same reaction pattern was observed for 1,2-dimethoxy-ethane, and we identified the oxidative cleavage product 11,analogous to 10 (Scheme 6), although we could not detect the

precursor dienol ether. Thus, the formation of an oxonium saltby β-H elimination involving the methylene group in DME isthe most likely pathway. These results agree with the work ofLautens et al., who used DME as a reduction reagent andidentified the methylene group of this solvent as the hydrogensource.3 The methylene group of DME is more reactive thanthe methyl group even if a β-H elimination is statistically morefavorable in the latter case. The thermodynamic stability of theoxonium salt represented in Scheme 6, higher than theexpected one from reaction of the methyl group, may drivethe decomposition reaction.

■ CONCLUSIONSThe formation of reduction products in reactions involvingpalladium aryl compounds, whether as reagents, as inter-mediates, or as catalysts, can sometimes be due to reaction withthe solvent. At high temperature, N-alkyl amides, ketones withβ-hydrogens, and diethers such as 1,4-dioxane or DME can be ahydride source in the presence of palladium complexes by β-Helimination. For palladium hydrocarbyl complexes, this leads toreduction products, RH, and Pd(0). β-H elimination occurs in a

palladium enolate for ketones or in a coordinated ether for 1,4-dioxane or DME. In contrast to former proposals, N-alkylamides form Pd-H species predominantly by β-H elimination ina N-coordinated complex and not by reaction with hydrolysisproducts such as amines. Since the presence of oxygen amplifiesthis effect, we propose that reoxidation of Pd(0) to Pd(II) byoxygen regenerates active species for hydride formation.Among these risky solvents, their coordination ability is an

important factor controlling further reaction by β-Helimination, as it has been shown for the three amides tested.DMA is the least coordinating and safest amide followed byNMP and DMF. This is especially relevant when the so-called“ligandless catalyst systems” are used (simple palladium salts,i.e., palladium chloride, acetate, etc., with no more ligands thanthe solvent, the reagents, and the products). From a practicalpoint of view amides, ketones, 1,4-dioxane, and DME should beavoided in aerobic conditions, and, in the presence of bases,ketones are especially high-risk followed, to a smaller extent, byamides.Other solvents such as THF, nitriles, toluene, and water are

quite safe and can be used at high temperatures in the presenceof base or oxygen with no reduction of Pd-aryl species.

■ EXPERIMENTAL SECTIONGeneral Methods. 1H and 19F NMR spectra were recorded using

Bruker AV-400 and Agilent MR-500 instruments at 293 K. Chemicalshifts (δ) are reported in ppm and referenced to Me4Si (

1H) or CFCl3(19F). Most NMR spectra were recorded in protic solvents using anacetone-d6 capillary as external reference. GC-mass spectra wererecorded on a Thermo Scientific Focus DSQII system. Solvents werepurchased from Aldrich, BDH-Prolabo, and Panreac (>99%) and wereused without further purification. Palladium complexes[PdCl2(NCMe)2],

36 (NBu4)2[Pd2(μ-Br)2Br2(C6F5)2],13 [PdBr(C6F5)-

(AsPh3)2],13 (NBu4)2[Pd2(μ-Br)2Br4],

37 and (NBu4)2[Pd2(μ-Br)2(C6F5)4]

38 were prepared according to procedures reported inthe literature. The organic compounds described are known,and mostof them commercially available. Their characterization data in theconditions detected are given below. Chemical shifts were comparedwith authentic commercial samples in the same conditions.

Decomposition Experiments of Complex 1 in DifferentSolvents. Procedure Followed for Reactions Under a N2Atmosphere without Base. Reaction in DMF. A Schlenk tube wascharged with 1 (50.0 mg; 0.0370 mmol) and deoxygenated DMF (1.0mL; 13.0 mmol) under nitrogen. The tube was sealed, and the mixturewas stirred at 100 °C for 2 h. The reaction mixture was allowed to coolto room temperature. The solution was checked by 1H NMR, 19FNMR, and GC-MS.

Procedure Followed for Reactions under a N2 Atmosphere withBase. Reaction in DMF. A Schlenk tube was charged with 1 (50.0 mg;0.0370 mmol), NaOH (10 μL; 7.5 M in H2O, 0.0750 mmol), anddeoxygenated DMF (1.0 mL; 13.0 mmol) under nitrogen. Thesolution was stirred at 100 °C for 2 h. The reaction mixture wasallowed to cool to room temperature. The solution was checked by 1HNMR, 19F NMR, and GC-MS.

The same procedure was followed for the reactions carried outunder air or under oxygen. All the reactions shown in Table 1 werecarried out in a similar way, just using the appropriate solvent insteadof DMF. The decomposition products and the relevant character-ization data in the conditions detected for each case are given below.

Dimethylformamide. HC(O)NHCH3 (2a).1H NMR (400 MHz, δ,

DMF/acetone-d6 capillary): 7.64 (s, 1H, HCO), 2.20 (d, J = 4.8 Hz,3H, CH3NH). MS (EI, m/z (%)): 59 (100) [M+].

{HC(O)}2NMe (3a). 1H NMR (400 MHz, δ, DMF/acetone-d6capillary): 8.67 (s, 2H, HCO). MS (EI, m/z (%)): 87 (4) [M+], 59(100) [M+ − CO].

C6F5H.19F NMR (376 MHz, δ, DMF/acetone-d6 capillary): −139.5

(m, 2F, Fortho), −155.4 (t, J = 20.20 Hz, 1F, Fpara), −163.2 (m, 2F,

Scheme 5. Decomposition of 1 in 1,4-Dioxane and ReactionsThat Follow

Scheme 6. Decomposition of 1 in DME

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Fmeta).1H NMR (400 MHz, δ, DMF-d7/acetone-d6 capillary): 7.32 (m,

3JH−F = 10 Hz, 4JH−F = 7 Hz, 5JH−F = 2 Hz). MS (EI, m/z (%)): 168(100) [M+], 149 (10) [M+ − F], 137 (15) [M+ − CF], 118 (10) [(M+

− CF) − F], 99 (60) [(M+ − CF − F) − F].C6F5D.

19F NMR (470 MHz, δ, DMF/acetone-d6 capillary): −139.8(m, 2F, Fortho), −155.4 (t, J = 20.2 Hz, 1F, Fpara), −163.3 (m, 2F,Fmeta). MS (EI, m/z (%)): 169 (100) [M+], 150 (10) [M+ − F], 138(15) [M+ − CF], 119 (10) [(M+ − CF) − F], 100 (60) [(M+ − CF −F) − F].Dimethylacetamide. CH3C(O)NHCH3 (2b).

1H NMR (400 MHz,δ, DMA/acetone-d6 capillary): 7.35 (b, 1H, CH3NH), 2.03 (d, J = 4.5Hz, 3H, CH3NH). MS (EI, m/z (%)): 73 (100) [M+], 58 (40) [M+ −Me].CH3C(O)NMeC(O)H (3b). 1H NMR (400 MHz, δ, DMA/acetone-d6

capillary): 8.66 (s, 1H, HCO), 1.92 (s, 3H, CH3CO). MS (EI, m/z(%)): 101 (100) [M+], 87 (20) [M+ −Me], 72 (85) [M+ − HCO], 57(40) [(M+ − HCO) − Me].

N-Methylpyrrolidone. C(O)−CH2−CH2−CH2−NC(O)H (4). 1HNMR (400 MHz, δ, NMP/acetone-d6 capillary): 8.18 (s, 1H,HCO). MS (EI, m/z (%)): 113 (8) [M+], 85 (100) [M+ − CO],57 (35) [(M+ − CO) − CO].Cyclohexanone. Cyclohexenone (7). 1H NMR (400 MHz, δ,

cyclohexanone/acetone-d6 capillary): 6.52 (dt, J = 10.2, 4.1 Hz, 1H,−CH2CHCHCO), 5.36 (dt, J = 10.2, 1.9 Hz, 1H, −CH2CHCHCO).MS (EI, m/z (%)): 96 (30) [M+], 68 (100) [M+ − CO].PhOH (8). 1H NMR (400 MHz, δ, cyclohexanone/acetone-d6

capillary): 6.61 (dd, J = 7.1, 7.8 Hz, H, Hmeta), 6.34 (d, J = 7.8 Hz,2H, Hortho), 6.22 (t, J = 7.1 Hz, 1H, Hpara). MS (EI, m/z (%)): 94(100) [M+], 66 (30) [M+ − CO].1,4-Dioxane. 1,4-Dioxene (9). 1H NMR (400 MHz, δ, dioxane/

acetone = 1:1/acetone-d6 capillary): 5.65 (s, 2H, −O-CHCH-O−),3.73 (s, 4H, −O-CH2-CH2-O−). MS (EI, m/z (%)): 86 (70) [M+], 84(100) [M+ − 2H].HC(O)OCH2CH2OC(O)H (10). 1H NMR (400 MHz, δ, dioxane/

acetone = 1:1/acetone-d6 capillary): 7.83 (s, 2H, HC(O)OCH2−),4.09 (s, 4H, HC(O)OCH2. MS (EI, m/z (%)): 72 (20) [M+ −CO2H2], 60 (100) [M+ − CO2CH2].1,2-Dimethoxyethane. HC(O)OCH3 (11).

1H NMR (400 MHz, δ,DME/acetone-d6 capillary): 7.73 (s, 1H, HC(O)OCH3). MS (EI, m/z(%)): 60 (85) [M+], 31 (100) [M+ − HC(O)].

■ ASSOCIATED CONTENT*S Supporting InformationAdditional experiments, NMR data for C6F5H in differentsolvents, and illustrative spectra for the experiments described.This material is available free of charge via the Internet athttp://pubs.acs.org.

■ AUTHOR INFORMATIONCorresponding Author*E-mail: albeniz@qi.uva.es.

NotesThe authors declare no competing financial interest.

■ ACKNOWLEDGMENTSFinancial support from the Spanish MINECO (DGI, grantCTQ2010-18901/BQU), the MEC (FPU fellowship toJ.A.M.T.), and the Junta de Castilla y Leo n (grantVA373A11-2) is gratefully acknowledged.

■ REFERENCES(1) (a) Metal Catalyzed Cross-Coupling Reactions; Meijere, A.Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004. (b) Tsuji, J.Palladium Reagents and Catalysts: New Perspectives for the 21st Century;Wiley-VCH: Weinheim, 2004.

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