ESI-MS Insights into Acceptorless Dehydrogenative Coupling of

Research Article pubs.acs.org/acscatalysis

ESI-MS Insights into Acceptorless Dehydrogenative Coupling of Alcohols Cristian Vicent*,† and Dmitry G. Gusev*,‡ †

Serveis Centrals d’Instrumentació Cientı ́fica, Universitat Jaume I, 12071 Castellón, Spain Department of Chemistry and Biochemistry, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5, Canada

‡

S Supporting Information *

ABSTRACT: Acceptorless dehydrogenative coupling (ADC) reactions catalyzed by a series of Ru and Os complexes were studied by ESI-MS. Important ethoxo, 1-ethoxyethanolate, and hydride intermediates were intercepted in the ADC of ethanol to ethyl acetate. Collision-induced dissociation (CID) experiments were applied as a structure elucidation tool and as a probe of the propensity of the reaction intermediates to evolve acetaldehyde, ethyl acetate, and H2, relevant to the catalytic cycle. The key mechanistic step producing ethyl acetate from the 1ethoxyethanolate intermediates was documented. Energydependent CID experiments demonstrated the importance of a vacant coordination site for efficient production of ethyl acetate. The versatility and potential broad applicability of ESI-MS and its tandem version with CID was further illustrated for the ADC reaction of alcohols with amines, affording amides. A mechanism related to that found for the ester synthesis is plausible, with the key step involving formation of a hemiaminaloxide intermediate. KEYWORDS: catalytic hydrogenation, pincer complexes, acceptorless dehydrogenation, electrospray ionization, collision induced dissociation

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dehydrogenated by the catalyst to yield the final ester or amide products, respectively.1a The detection of intermediates is important in a mechanistic study; however, this task is anticipated to be anything but trivial because of the short-lived transient nature of the intermediates under catalytic ADC conditions (typically at T ≥ 80 °C). Indeed, monitoring metal species formed under the operating catalytic conditions of reactions in Scheme 1a,b remains virtually unexplored. In this respect, electrospray ionization mass spectrometry (ESI-MS) has become a valuable tool for studying fast transformations8 by providing snapshots of the dynamic ionic composition of the reaction solutions. Collisioninduced dissociation (CID) experiments further contribute to the utility of mass spectrometry as a mechanistic tool in organometallic chemistry.9 Convenient sample introduction techniques allow chemical reactions to be monitored in situ even at high operating temperatures, with minimal sample manipulation. In this context, McIndoe’s group recently described the pressurized sample infusion technique coupled directly to the mass spectrometer that proved to be particularly useful.10 Herein, we applied ESI-MS for detection of ADC reaction intermediates under catalytic conditions. Pincer-type complexes 1−5 bearing PyNP,11 SNS,12 PNP,13 and PyNNP14 ligands

INTRODUCTION Acceptorless dehydrogenative coupling (ADC) of alcohols according to Scheme 1a,b is an atom-economical and environmentally benign method for the production of esters and amides.1 The reverse hydrogenation (HY) process is also feasible, since the HY/ADC reactions are mechanistically related, and ADC catalysts have demonstrated useful activity in ester and amide hydrogenation.2 Milstein’s group developed the first efficient homogeneous catalysts for the syntheses of esters from primary alcohols3 and amides from alcohols and amines.4 Subsequently, a series of Ru and Os catalysts have been prepared demonstrating improved reaction efficiency and selectivity.2b,5,6 The continuing growth in HY/ADC catalyst development is in contrast with a relatively small number of examples dedicated to the elucidation of the reaction mechanism. Some insights have been derived from (i) the presence or, more commonly, absence of NMR-observable intermediates during the catalytic reactions, (ii) stoichiometric reactions under relevant conditions, and (iii) DFT calculations.7 The intermediacy of alkoxo and dihydride species was proposed for the Milstein catalyst, in a sequence defined by alcohol addition, followed by β-hydrogen elimination with concomitant formation of the corresponding aldehyde (Scheme 1c). Ultimately, the dihydride eliminates H2, thereby regenerating the catalyst. Independently, the aldehyde reacts with the alcohol or amine substrate to afford the corresponding hemiacetal or hemiaminal intermediates that are © XXXX American Chemical Society

Received: March 1, 2016 Revised: April 5, 2016

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DOI: 10.1021/acscatal.6b00623 ACS Catal. 2016, 6, 3301−3309

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Scheme 1. (a, b) Dehydrogenative Coupling of Alcohols To Yield Esters and Amides, (c) Schematic Representation of the Intermediates Proposed for the Milstein Catalyst, and (d) Complexes 1−5 Studied in This Work

with ethanol (or ethanol doped with NaBF4) using a T-shaped connection directly coupled to an ESI source (see Figure S1 in the Supporting Information).10d We also attempted monitoring reaction intermediates by taking aliquots at different time intervals followed by an off-line dilution with EtOH, but this approach did not allow detecting most of the intermediates involved; instead, oxidized species due to the formal uptake of oxygen were dominant. Establishing the composition of all metal-containing species was facilitated by the characteristic isotopic pattern at natural abundance of Ru and Os, and it was carried out by comparison of the experimental and theoretical isotope patterns using the MassLynx program 4.1. For the CID experiments, the cations of interest were mass-selected using the first quadrupole (Q1) and interacted with argon in the collision cell at variable collision energies (Elaboratory = 3−20 eV). The ionic products of fragmentation were analyzed with a time-of-flight analyzer (for the QTOF instrument) or the second quadrupole (for the Quattro LC QqQ instrument). The isolation width was 1 Da, and the most abundant isotopomer was mass-selected in the first quadrupole analyzer.

(Scheme 1d) are efficient for hydrogenation of a range of substrates (esters, ketones, imines) as well as for the acceptorless dehydrogenative coupling of alcohols. Recently, we studied the mechanism of the ADC reactions of methanol and ethanol catalyzed by 5 using a combination of ESI-MS experiments with DFT calculations.14 The versatility of the ESIMS technique is further underscored in the present investigation of a broader spectrum of catalysts with different efficiencies in ADC of alcohols aimed at establishing whether a common mechanism might be operative in all cases. Moreover, an investigation of the related dehydrogenative reaction, the ADC of ethanol and primary amines to yield acetamides, is also presented.

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EXPERIMENTAL SECTION

Electrospray Ionization Mass Spectrometry (ESI-MS) and Collision-Induced Dissociation (CID). ESI-MS studies were conducted on a QTOF Premier or a Quattro LC (QqQ) instrument, equipped with an orthogonal Z-spray-electrospray interface (Waters, Manchester, UK). A capillary voltage of 3.5 kV was used in the positive ESI(+) scan mode, and the cone voltage was adjusted to a low value (typically Uc = 5−15 V) to control the extent of fragmentation in the source region. The Q-TOF instrument was operated in the W mode at a resolution of ca. 15000 (fwhm). Nitrogen as the drying and cone gas was set to flow rates of 300 and 30 L/h, respectively. For the Quattro LC instrument, the desolvation and nebulization gas was nitrogen set to flow rates of 400 and 90 L/h, respectively. As mentioned above, both ester hydrogenation and ADC of alcohols are expected to follow the same mechanism; however, online monitoring of the ADC reaction by ESI-MS is operationally simpler, as it avoids the use of high H2 pressure. Catalytic runs were monitored for 3 h using 0.01 or 0.05% of catalyst and 1% of NaOEt with respect to ethanol. Sample solutions were delivered to the spectrometer at different time intervals using the pressurized sample infusion (PSI) technique. Attempts to use continuous delivery of the reaction mixture, which contains NaOEt (the base in all ADC reactions), caused progressive reduction of the ion abundances for all species in the ESI mass spectra, accompanied by deposition of nonvolatile colorless solids in the ESI chamber. This technique has proved to be ideal for in situ analysis of complex mixtures formed during catalysis.10a−c Typically, a N2 positive pressure (1−3 psi) was used to transfer sample solutions that were further diluted

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RESULTS AND DISCUSSION Single-Stage ESI-MS. Studying a chemical system by ESIMS requires that the species must be charged. Two aspects make the catalytic chemistry of Scheme 1 particularly suitable for an ESI-MS investigation. On the one hand, using the catalysts with excess base (NaOEt) produced a useful enhancement of the ion abundances of the [M + Na]+ sodium adducts.15 On the other hand, since ethanol served as both the substrate and the solvent, the ion suppression effects due to the excess of substrate16 were not encountered in the present study. Thus, high catalyst loadings were not necessary and realistic catalytic conditions could be used for the ESI-MS reaction monitoring. For complexes 1−5, observed ionizations typically involved chloride or hydride (Cl− or H−) loss. In ethanol, the most favorable ionization process was the M−Cl bond breaking that produced [1 − Cl]+ and [2 − Cl]+ cations as the base peaks for 1 and 2, respectively. For 3, the [3 − H]+ cation was observed as the dominant species, whereas for 4 and 5, the [4 − Cl]+ and [5 − Cl]+ cations accompanied by [4 − H]+ and [5 − H]+ were detected, the last two albeit with much lower ion abundances. The alkali ion adduct formation could be promoted by addition of NaBF4.10d,17 The observations of the original compounds as 3302


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In addition to peaks due to 1 (peaks at m/z 719.2, 777.2, and 793.1 assigned to [1 − Cl]+, [1 + Na]+ and [1·O + Na]+, respectively), the ethoxo intermediate 1b was observed during the first 30 min as [1b − H]+ at m/z 729.2, whereas 1c (manifested as [1c − H]+ and [1c + Na]+ at m/z 773.2 and 797.1, respectively) was dominant after 1 h from the start of the reaction (see Figure 1). Species 1d (and in general the related dihydrides formed from complexes 2−4) was not detected as the [1d + Na]+ adduct because of its low abundance.18 The low abundance of 1d−4d suggests that they are most likely not involved in a rate-limiting step along the catalytic cycle. The presence of mixed Cl/H and Cl/1-ethoxyethanolate (C4O2H9) ligand complexes, namely RuCl(H)(PPh3)(PyNHP) (1e) and RuCl(C4O2H9)(PPh3)(PyNHP) (1f) (see Table S1 in the Supporting Information for details), was also evident in the early stages of the ADC reaction. For example, species 1e,f (manifested as [1e + Na]+ and [1f + Na]+ at m/z 743.2 and 831.2, respectively) were evident in the ESI mass spectrum after 1 h. The observation of both groups of intermediates 1b,c and 1e,f highlights the versatility of the ESI-MS technique in unraveling complex transformations. Formation of side products such as acetate species or oxidized species (formally corresponding to mass increases of 16 and hereafter formulated as M·O species) was also observed. For instance, the acetatecontaining intermediate 1g was observed as [1g − Cl]+, [1g + Na]+, and [1g·O + Na]+ cations at m/z 743.2, 801.1, and 817.0, respectively, upon ESI-MS. CID mass spectra confirmed the presence of the acetates as judged by the release of acetic acid (Δm = 60) as a fragmentation channel. We believe that this high reactivity of catalysts 1 and 2, in terms of the large number of products identified from them, correlates with their high ADC activity (see further discussion below for 4). The putative 16-electron amido intermediates 1a and 2a were not observed by ESI-MS under the catalytic conditions. This is rationalized by recognizing their intrinsic reactivity toward ethanol leading to 1b and 2b,11b,12 respectively, and by taking into the consideration the large excess of ethanol with respect to ruthenium under the catalytic conditions. When dimer 3 was used as the catalyst, the initial intensity of the ESI-MS detected dimeric species [3 − H]+ at m/z 941.2 was significantly reduced relative to a new set of mononuclear complexes. This is clearly illustrated in Figure 2, showing the ESI mass spectrum of the ADC reaction of ethanol catalyzed by 3. In this case, intermediates 3b,c (expected to be structurally analogues to 1b,c) could be identified by ESI-MS as [3b − H]+ and [3c − H]+ at m/z 517.1 and 561.2, respectively. Other side products featuring acetate and oxidized species were also evidenced (see Figure S3 in the Supporting Information). Dimeric species were invariably observed during the catalytic reaction, thus suggesting the role of the dinuclear complexes as

sodium ion adducts is anticipated to be crucial to unambiguously determine the intact coordination environment at the metal site during catalysis. Acceptorless Dehydrogenative Coupling (ADC) of Ethanol To Yield Ethyl Acetate. In this section, we discuss ESI-MS detection of intermediates relevant to the ADC of ethanol while using the pressurized sample infusion (PSI) technique.10 In the reactions investigated herein, NaOEt base in the catalytic system produces significant ion abundances of Na+ adducts. Chemical speciation of the reaction of Scheme 2 was Scheme 2. ADC of Ethanol

practically the same on catalysis by 1 or 2, in terms of both the nature of the detected Ru species and their temporal evolution. Formation of intermediates 1b,c (see Scheme 3 for the Scheme 3. Reaction Intermediates in ADC of Ethanol Catalyzed by 1

proposed structures) was evident from the ESI-MS analysis on the basis of the m/z values and isotopic patterns, as illustrated in Figure 1 for the catalytic reaction using 1 monitored after 1 h. Table S1 in the Supporting Information collects the m/z values for the identified species. The analogous intermediates 2b,c, structurally related to 1b,c by replacement of the PyNHP by the SNHS ligand, were detected by ESI-MS in the ADC reaction catalyzed by 2. Catalyst 1 and intermediate 1c were both detected as intact Na+ ion adducts under the catalytic conditions. In general, the ion abundances of Na+ adducts were strongly affected by the intrinsic chemical composition of each intermediate. For example, chlorine-containing species were clearly observed as Na+ adducts due to the well-known stabilizing effect of the Ru− Cl··Na interaction in the gas phase.10d 1-Ethoxyethanolate intermediate 1c could be readily identified as a Na+ ion adduct, whereas dilution with ethanol in the presence of traces of NaBF4 was required to visualize the intact Na+ ion adduct of the ethoxo intermediate 1b.

Figure 1. ESI mass spectrum recorded via the PSI technique after 1 h, using a triple-quadrupole analyzer. Relevant ethoxo and 1-ethoxyethanolate intermediates are [1b − H]+ at m/z 729.2 and [1c − H]+ and [1c + Na]+ at m/z 773.2 and 797.1, respectively. Peak assignments of all observed species are described in the text. 3303


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Figure 2. ESI mass spectra of ethanol (2 mL) in the presence of 0.05 mol % of 3 (top) and 0.05 mol % of 3 and 1 mol % of EtONa after heating 30 min under reflux (bottom), using the Q-TOF instrument. The base peak corresponds in both cases to the dimer [3 − H]+ cation (m/z 941.2). Intermediates 3b,c were identified as [3b − H]+ and [3c − H]+ at m/z 517.1 and 561.2, respectively.

Scheme 4. Fragmentations Observed upon CID of Mass-Selected [1b + Na]+ and [1b − H]+ Cations Derived from the ESI-MS Analysis of 1b

a continuous reservoir of the mononuclear active catalyst. The low intensity of the mononuclear species hindered the identification of the intrinsically low abundance Na+ ion adducts in the present case. Unlike complexes 1−3, which proved to be efficient in the ADC reaction of ethanol to ethyl acetate,11,12 complex 4 gave lower conversions.11b We decided to explore the latter to ascertain the nature of species formed from 4 in the catalytic solution. The chemical speciation of the ADC reaction catalyzed by 4 was virtually identical with that observed for 1 and 3 in terms of the identity of the metal-containing species; however, formation of the intermediates was significantly retarded (see Figure S4 in the Supporting Information for details) and the ESI mass spectra were less crowded. In particular, the acetate and oxidized species that were observed for compounds 1−3 and 5 were detected only as minor species with 4. The enhanced stability of the reaction intermediates

formed from 4 was clearly evident and might correlate with the reduced catalytic activity of this complex.19 Collision-induced dissociation CID experiments constitute a powerful technique for probing the structure and reactivity of reaction intermediates.9 For example, CID experiments on the sodium ion adducts of 1b,c aided in their structural assignment since liberation of the neutrals, NaOEt and NaC4O2H9, respectively, strongly supports the structures of Scheme 3. Moreover, the CID experiments revealed the intrinsic propensity of the ethoxo, 1-ethoxyethanolate, and dihydride intermediates to release neutral species relevant to the catalytic cycle of the ADC of ethanol. A summary of the fragmentation pathways of mass-selected [1b + Na]+ and [1b − H]+ cations is presented in Scheme 4. CID of [1b + Na]+ resulted in liberation of NaOEt as the dominant fragmentation pathway, whereas [1b − H]+ eliminated EtOH as the main dissociation process. Release of acetaldehyde was also observed from both [1b − H]+ and [1b + Na]+, but with a lower abundance. These 3304


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Figure 3. CID mass spectra of (a) [1b − H]+ (m/z 729.2), (b) [2b − H]+ (m/z 602.2), (c) [3b − H]+ (m/z 517.1), and (d) [4b − H]+ (480.2), recorded at CEElab = 10 eV.

Scheme 5. Proposed Reactions Linking the Intermediates 1a−c

Figure 4. CID mass spectra of the (a) [1c − H]+ (m/z 773.2) and (b) [2c − H]+ (m/z 646.2) cations recorded at CEElab = 10 eV.

PNN complexes.7a,f The absence of NMR-observable free aldehyde during the catalytic reactions of 111,12 and the dominant nondehydrogenative fragmentation pathway observed in the CID experiments suggest that 1b′ may rapidly re-form the alkoxide 1b or, alternatively, it is rapidly attacked by the solvent, EtOH. The latter reaction possibly leads to the unstable dihydrogen intermediate 1c′, which was not detected by ESI-MS, ultimately leading to the experimentally detected intermediate 1c. The reversibility of coordinated aldehyde and alkoxo ligands in the periphery of the metal has been emphasized theoretically and proved to be crucial to trigger hemiacetal formation to ultimately yield the ester.7b The intermediacy of hemiacetals in the ADC of alcohols was envisioned by Murahashi20 and Shvo21 and later invoked by others.3,22 Bergens demonstrated formation of a hemiacetaloxide complex in the reaction of RuH2((R)-BINAP)((R,R)dpen) with γ-butyrolactone,23 while Milstein succeeded in selectively forming acetals24 as the reaction products during the catalytic transformation of primary alcohols with the liberation

results suggest that the ethoxides are more prone to eliminate ethanol rather than the product of ethanol dehydrogenation, acetaldehyde. Identical trends were observed upon CID of [2b − 4b − H]+ and [2b − 4b + Na]+ cations (see Figure 3 for illustrative CID mass spectra). The dominant observation of neutral losses, EtOH and EtONa, in the CID spectra of [1b − H]+ and [1b + Na]+, respectively, agrees with the equilibrium between 1b and the 16-electron amido complex 1a via ethanol elimination as depicted in Scheme 5. The release of acetaldehyde from 1b in the gas phase, even if it is barely detectable, is indicative of formation of the acetaldehyde intermediate 1b′ presumably (but not necessarily)7b via β-hydrogen elimination in a 16electron intermediate with an uncoordinated Py group (see Scheme 5).3 Let us note that an alternative mechanism might be responsible for the acetaldehyde formation; e.g., recent computational work indicated that the inner-sphere mechanism is energetically less favorable than the outer-sphere mechanism, via bifunctional hydrogen transfer, for a series of ruthenium 3305


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Scheme 6. Fragmentation Pathways Observed upon CID Conditions of Mass-Selected [1c + Na]+ and [1c − H]+ Cations Derived from ESI-MS of 1c

Scheme 7. Proposed Sequence of Reactions of 1c To Yield 1d and Ethyl Acetate, Followed by Regeneration of 1a

in the 16-electron [1c−4c − H]+ cations. We should note that the vacant coordination site in [1c−4c − H]+ would not necessarily be trans to the hemiacetaloxide as shown in Scheme 6 but may be located cis to the hemiacetaloxide, considering the facile mer/fac isomerization well-documented for the SNS and PNN complexes.11,12 A vacant site cis to the hemiacetaloxide would facilitate β-hydrogen elimination leading to ethyl acetate. As mentioned above, intermediates 1d−4d were not observed experimentally because of their low stability under catalytic conditions; however, they could be evidenced in the gas phase as the product ions from ethyl acetate liberation of 1c−4c that subsequently liberate H2 (see Figure 4). This latter elementary step corresponds to 1d to 1a transformation and catalyst regeneration, as illustrated in Scheme 7. Acceptorless Dehydrogenative Coupling (ADC) of Ethanol and Amines To Yield Acetamides. Recently, we reported that OsHCl(CO)[PyNNP] (5; Scheme 1) is efficient for dehydrogenative coupling of alcohols and amines without solvent and under relatively mild conditions.14 For example, heating ethanol with benzylamine (1/1) in the presence of 0.05 mol % of 5 afforded N-benzylacetamide (see Scheme 8) in 96% yield after 17 h. No initiation time was manifested, and a constant H2 bubbling was evidenced as the reflux temperature was reached.14 Using the pressurized sample infusion technique coupled with ESI-MS, we undertook a study of the reaction intermediates relevant to this process during the first 3 h. We succeeded at intercepting a hemiaminaloxide species, 5c (Figure 5), identified on the basis of the m/z value, isotopic pattern, and CID experiments. This intermediate was observed by ESI-MS, and its relative abundance remained practically

of H2, using an acridine-based ruthenium pincer complex. Except for our recent report,14 formation of hemiacetals in the catalytic ADC reactions of alcohols has not been observed, neither as free species nor as hemiacetaloxide ligands coordinated to a metal center. We performed CID experiments to ascertain the intrinsic reactivity of the 1-ethoxyethanolate intermediate 1c. The CID spectra are exemplified in Figure 4 for [1c − H]+ and [2c − H]+ cations. Gas-phase fragmentation reactions of the ESI-MS detected species [1c − H]+ and [1c + Na]+ produced ethyl acetate as a fragmentation channel. Additionally, the CID mass spectra of [1c + Na]+ displayed liberation of sodium ethoxyethanolate. The fragmentation reactions depicted in Scheme 6 are also characteristic of the related 1-ethoxyethanolate intermediates 2c−4c in the catalytic solutions of 2−4. It is worth emphasizing that the CID spectra of [1c − H]+, [2c − H]+, [3c − H]+, and [4c − H]+ all displayed exclusive liberation of ethyl acetate followed by H2, thus indicating the central role of the metal hemiacetaloxide intermediates in the ADC reaction. The product ester formation presumably occurs via β-hydrogen elimination from a 16-electron hemiacetaloxide intermediate, for example, 1d′ in Scheme 7 where the hemilability of the pincer ligand plays a major role, to yield the dihydride 1d that subsequently eliminates H2 to produce 1a (see Scheme 7). In this respect, a relevant observation was made during the energyresolved CID experiments of [1c−4c − H]+ cations, which produced ethyl acetate at significantly lower collision energies than the corresponding [1c−4c + Na]+ species. This difference can be attributed to the presence of a vacant coordination site 3306


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Scheme 8. Formation of N-Benzylacetamide

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CONCLUSIONS Whereas ESI-MS25 and desorption electrospray ionization mass spectrometry (DESI-MS)26 have been used for studies of ruthenium-catalyzed hydrogenations, these techniques have received little attention in mechanistic studies of catalytic alcohol dehydrogenation reactions.14,27 In this paper, the ESIMS and CID experiments were used as structure elucidation tools, to unravel the intrinsic reactivity of reaction intermediates in acceptorless dehydrogenative coupling (ADC) reactions of ethanol catalyzed by a series of pincer-type Ru and Os complexes. A series of intermediates comprising metal ethoxo, 1-ethoxyethanolate, and hydride functional groups were intercepted and characterized during the ADC of ethanol to yield ethyl acetate; their compositions were ascertained via the detection of the intact alkali ion adducts [M + Na]+. A functional group−reactivity relationship could be established where the ethoxides were shown to be involved in the reversible liberation of ethanol and/or formation of acetaldehyde, the metal dihydrides exhibited a strong tendency toward H2 elimination, and the key 1-ethoxyethanolate intermediates preferentially liberated ethyl acetatethe ultimate product of the ADC reaction. A mechanistically related ESI-MS study of the ADC of alcohols and amines allowed us to intercept and characterize the metal-containing hemiaminaloxide reaction intermediates. It is well-recognized that catalytic hydrogenation of carbonyl compounds and the reverse alcohol dehydrogenation can proceed in an inner- and/or outer-sphere fashion. The latter process is unique among the organometallic mechanisms by avoiding substrate binding to the metal center of the catalyst; therefore, the concerted process of H2 transfer from (or to) the metal takes place via fleeting intermediates where the substrate is only loosely connected with the catalyst. While the power of mass spectrometry in detecting short-lived reaction intermediates is impressive, it is nevertheless unlikely that the catalytic outer-sphere H2 transfer reactions can be followed and documented by MS techniques. It is conceivable that

unchanged for 3 h. When ethanol was reacted with nbutylamine, the corresponding hemiaminaloxide intermediate could also be observed by ESI-MS. Under the CID conditions, the hemiaminaloxide intermediates exhibited liberation of the corresponding acetamides as fragmentation pathways. Figure 5b illustrates the gas-phase reactivity of the mass-selected [5c − H]+ cation that comprises amide formation accompanied by H 2 loss. A minor fragmentation channel that resulted in elimination of the free amine was also evident. We further notice that no dihydride intermediate 5d (analogues to 1d−4d) could be detected by ESI-MS; this is in agreement with the known instability of 5d with respect to H2 loss in solution.14 The experimental evidence of Figure 5 suggests that hemiaminaloxide complexes such as 5c are viable intermediates en route to amides in a way mechanistically analogous to that proposed for the hemiacetaloxide intermediates leading to esters in Scheme 7. The temporal evolution of the reaction intermediates and the CID experiments certainly suggest that the ADC of alcohols and amines might follow closely related mechanisms. We hypothesize that the diverging step is the addition of the alcohol vs amine to the coordinated aldehyde intermediate, as illustrated in Scheme 5, to form a hemiacetaloxide vs hemiaminaloxide intermediate that subsequently evolves to the ester or amide product, respectively.

Figure 5. (a) Pressurized sample infusion (PSI) ESI mass spectrum of a sample from the catalytic reaction of Scheme 8. (b) CID mass spectrum of the mass-selected hemiaminaloxide [5c − H]+. 3307


Research Article

ACS Catalysis

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complexes 1−5 studied here can act as both inner- and outersphere catalysts, and the two mechanisms are most likely in competition in the hydrogenation/dehydrogenation reactions. Additionally, solvation can play a crucial role by triggering some of the elementary steps occurring in solution.7 It is the extreme power of mass spectrometry in detecting gaseous species present in vanishingly low concentrations that, ironically, makes it challenging to claim with enough certainty that the intermediates documented in this work represent the principal reaction pathway and thus “the mechanism” of the ADC reactions of ethanol. The inner-sphere ADC mechanism is distinctly different from the outer-sphere process by involving a coordinated aldehyde intermediate, formed via the classical β-hydrogen elimination. The latter requires an empty coordination site and a certain degree of lability/hemilability of the catalyst. In this regard, a comparative study of the catalysts of varying degrees of hemilability, also including stable complexes with all strongly bonded ligands, should provide important mechanistic insights. A fitting example from our own work is the comparison of RuHCl(CO)[HN(CH 2 CH 2 PPh 2 ) 2 ] and RuHCl(CO)[PyCH2NHCH2CH2PPh2]. These complexes gave 4700 and 4200 turnovers, respectively, in the ADC of refluxing ethanol to ethyl acetate in 24 h under equivalent reaction conditions.11b If the former catalyst retains an intact Ru[κ3-PNP] fragment at 78 °C, this would be an indication of the outer-sphere mechanism being the principal pathway. There is no doubt that future studies would furnish a definitive answer.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.6b00623. Schematic picture of the PSI ESI-MS experimental setup, additional ESI-MS data, and peak assignments for various samples (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail for C.V.: [email protected]. *E-mail for D.G.G.: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to the NSERC Canada, the Ontario Government, and Wilfrid Laurier University for financial support and the SCIC of the UJI for providing mass spectrometry facilities.

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REFERENCES

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ESI-MS Insights into Acceptorless Dehydrogenative Coupling of

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