Ru0 or RuII: A Study on Stabilizing the "activated" Form of Ru-PNP Complexes with Additional Phosphine Ligands in Alcohol Dehydrogenation and Ester Hydrogenation

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Ru⁰or Ru^II: A Study on Stabilizing the “Activated” Form of Ru-PNP

Complexes with Additional Phosphine Ligands in Alcohol

Dehydrogenation and Ester Hydrogenation

†

̈

Daniel J. Tindall, Maximilian Menche, Mathias Schelwies, Rocco A. Paciello, Ansgar Schafer,

Peter Comba, Frank Rominger, A. Stephen K. Hashmi, and Thomas Schaub *

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ABSTRACT: The complex Ru-MACHO has been previously shown

to undergo uncontrolled degradation subsequent to base-induced

dehydrochlorination in the absence of a substrate. In this study, we

report that stabilization of the dehydrochlorinated Ru-MACHO with

phosphines furnishes complexes whose structures depend on the

phosphines employed: while PMe₃led to the expected octahedral Ru^II

complex, PPh₃provided access to a trigonal-bipyramidal Ru⁰complex.

Because both complexes proved to be active in base-free (de)-

hydrogenation reactions, thorough quantum-chemical calculations

were employed to understand the reaction mechanism. The calculations show that both complexes lead to the same mechanistic

scenario after phosphine dissociation and, therefore, only diﬀer energetically in this step. According to the calculations, the typically

proposed metal−ligand cooperation mechanism is not the most viable pathway. Instead, a metal−ligand-assisted pathway is

preferred. Finally, experiments show that phosphine addition enhances the catalyst’s performance in comparison to the PR₃-free

“activated” Ru-MACHO.

derivatives 1b¹⁴and 1c^9a,15requires a base (often employed in

INTRODUCTION

■

large excess) to generate the so-called “activated” 16-electron

The acceptorless dehydrogenative coupling of alcohols to esters

(“dehydrogenations”) and the reverse hydrogenation of esters to

alcohols with H₂catalyzed by homogeneous transition-metal

catalysts are of great interest to the chemical industry in the

Ru^IIcomplex after dehydrochlorination (i.e., in the case of Ru-

MACHO, complex 2) analogous to other pincer complex-

es.^{4c,11a,12a,16}While the dehydrochlorinated species for 1b^10b,j

and 1c^6d,16b,c,ehave been isolated and structurally characterized,

synthesis of bulk chemicals (eq 1).

structural characterization of 2 still remains elusive.¹⁷One

reason for this might be the low stability of 2, as reported by our

laboratory recently. In the absence of a substrate, the base-

induced dehydrochlorination of 1a was followed by immediate

degradation of the presumably formed 2. From the resulting

In contrast to heterogeneous processes, they can often be

conducted at milder reaction conditions, reducing side-product

formation.¹Additionally, (de)hydrogenations use smaller

amounts of catalysts and additives than the traditional methods

with stoichiometric reagents. This, consequently, renders work-

ups easier and reduces the amount of waste produced, which

becomes of great importance if reactions are conducted on a

larger scale. Since the pioneering work of Milstein et al.,²many

important contributions have been made in this ﬁeld.³One of

the systems that has been shown to be highly useful in many

important transformations (e.g., hydrogenation of esters⁴and

imines,⁵dehydrogenation of alcohols⁶and amines,⁷formic acid

decomposition,⁸CO₂reduction,^8,9and others,^7,10including

cross-coupling¹¹and deuteration reactions¹²) involves the

commercially available complex Ru-MACHO (1a, Scheme

1).^4a,13Ru-MACHO as well as its likewise commercial

plethora of ruthenium species, three could be characterized by

X-ray crystallography, and their structures suggested that ligand

fragmentation and reassembly must have taken place.¹⁸Among

these, the Ru⁰complex 3, bearing a tripodal tetradentate ligand

(Scheme 1), was selected for further studies and exhibited

excellent catalytic activity in the (de)hydrogenations without

any base necessary for activation (for hydrogenations with H₂,

activation by an alcohol was required). Complex 3 represents a

Received: February 4, 2020

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substituted the CO ligand with an N-heterocyclic carbene.

Although this allowed ester hydrogenations at relatively low

pressures, a large excess of base was still necessary.²⁵

Scheme 1. Previously Reported Substrate-Free Formation of

a Ru⁰Complex (3) and Envisioned Route to a Base-Free

Catalyst (4) through Stabilization of the “Activated” Ru-

a

MACHO (1a)

RESULTS AND DISCUSSION

■

Synthesis and Characterization of the Ru^IIComplex 5

and Ru⁰Complex 6. At the outset of this study, a cold solution

of KOtBu in tetrahydrofuran (THF-d₈) was added to a cold

suspension of Ru-MACHO and PMe₃in THF-d₈, resulting in an

immediate color change and the dissolution of all solids after

warming to room temperature and yielding a yellow solution,

1

which was analyzed by NMR spectroscopy. The H NMR

spectrum showed a doublet of triplets at −8.02 ppm (J = 104.8

and 20.5 Hz). In the ³¹P{¹H} NMR spectrum, two signals, a

doublet at 67.1 ppm (J = 20.7 Hz) and a triplet at −25.2 ppm (J

= 20.7 Hz) with an integral ratio of 2:1, were detected. The data

suggested that the desired complex 5 was formed selectively

Scheme 2. Synthesis of Ru^IIComplex 5 and Ru⁰Complex 6

a

Two other commercially available derivatives of Ru-MACHO that

require activation by a base (1b and 1c) and the base-free Ru-

MACHO-BH (1d) are depicted in the inset.

rare example of a Ru⁰precatalyst for alcohol dehydrogenations

and ester hydrogenations. Very recently, the group of Chianese

showed that their Ru^II-CNN complexes as well as Milstein’s

Ru^II-PNN complex can undergo base-induced dehydroalkyla-

tion, yielding the corresponding catalytically active Ru⁰

complexes in the presence of PCy₃.¹⁹While at the current

stage it remains unclear if these systems involve an on-cycle Ru⁰

(Scheme 2). Further analysis conﬁrmed this interpretation: the

¹³C{¹H} NMR spectrum shows a signal (triplet of doublets, J =

11.0 and 8.8 Hz) at 206.3 ppm, which was assigned to the

carbonyl carbon. The IR spectrum shows a carbonyl stretching

frequency at 1885 cm⁻¹, which is in agreement with the

literature data for related complexes (see, for example, ref 9a).

Crystals suitable for X-ray diﬀraction analysis were grown by

layering a benzene solution with pentane at room temperature.

The molecular structure of 5 shows a distorted octahedral

geometry in which PMe₃and the hydride ligand are oriented

trans to each other, while the tridentate amido ligand

coordinates in a meridional fashion (Figure 1). The fourth

coordination site of the equatorial plane is occupied by the CO

ligand. The distortion is most pronounced in the nonlinear

coordination of the two phosphine side arms to ruthenium [P1−

Ru1−P2, 158.52(2)°]. The Ru1−P3 distance [2.4007(5) Å] is

signiﬁcantly longer than the distances between the metal center

and the phosphorus atoms of the PNP ligand [Ru1−P1,

2.3037(5) Å; Ru1−P2, 2.3109(5) Å]. Furthermore, the higher

steric demand of PMe₃compared to the hydride ligand leads to a

greater distance of the two phenyl groups syn to PMe₃[C11···

C31, 7.045(2) Å] than the two phenyl groups syn to the hydride

ligand [C21···C41, 6.039(3) Å]. The distance Ru1−N1

[2.157(2) Å] is only slightly shorter than that in the parent

Ru-MACHO complex [2.174(2) Å⁸], indicating that the lone

pair on N1 is not contributing much to stabilization of the

ruthenium center because of the presence of the additional

phosphine ligand [in the related complex 1b, a much more

species, Grutzmacher and co-workers have demonstrated that

̈

their system converts methanol (MeOH) and H₂O into H₂and

CO₂via a Ru^II/Ru⁰cycle.²⁰

Because of its application potential, a robust and base-free

catalytic system is highly desirable.²¹The complex Ru-

MACHO-BH¹³(1d, Scheme 1) shows a high activity in alcohol

dehydrogenations as well as the hydrogenation of carbonyl

compounds in the absence of basic additives.^{4d,f,6d,21p,r,22}

−

Despite this and its commercial availability, the BH₄ligand

will decompose over time in these reaction mixtures by

alcoholysis, resulting in a diminished long-term stability of 1d.²³

Because the previously shown degradation of 1a, or rather 2, is

assumed to be problematic in many ways (e.g., loss of catalyst,

uncontrolled formation of side products, etc.), a study was

undertaken to evaluate the possibility of stabilizing the

unsaturated complex 2 by a neutral L-type ligand (Scheme

1).²⁴The hypothesized complexes of type 4 would, ﬁrst, be

expected to act as base-free catalysts in (de)hydrogenation

reactions, which would make them applicable to a broader scope

(e.g., to base-sensitive substrates) and would eliminate the

challenge of dealing with the remaining amounts of base and side

products thereof (e.g., salts) after the reaction is completed.

Second, the ligand L is hypothesized to increase the lifetime of

the catalyst in the reaction mixture and/or to aid in carrying the

catalyst from one substrate batch to the next one without

degradation. The only other Ru-MACHO-related system

bearing an L-type ligand was reported by Ogata et al., who

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Figure 1. Molecular structure of 5 in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms and one

molecule of cocrystallized benzene are omitted for clarity. Selected

distances (Å) and angles (deg): Ru1−C99, 1.848(2); Ru1−N1,

2.157(2); Ru1−P1, 2.3037(5); Ru1−P2, 2.3109(5); Ru1−P3,

2.4007(5); Ru1−H1, 1.62(2); C99−Ru1−N1, 178.24(7); C99−

Ru1−P1, 97.05(6); C99−Ru1−P2, 98.79(6); C99−Ru1−P3,

93.03(6); C99−Ru1−H1, 93.5(8); N1−Ru1−P3, 88.52(4); N1−

Ru1−H1, 84.9(8); P1−Ru1−P2, 158.52(2); P1−Ru1−P3, 97.17(2);

P2−Ru1−P3, 96.38(2); P3−Ru1−H1, 173.4(8).

Figure 2. Molecular structure of 6 in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms and one

molecule of cocrystallized benzene are omitted for clarity. Selected

distances (Å) and angles (deg): Ru1−C99, 1.809(9); Ru1−N1,

2.246(6); Ru1−P1, 2.296(2); Ru1−P2, 2.307(2); Ru1−P3, 2.330(2);

C99−Ru1−N1, 171.5(3); C99−Ru1−P1, 93.4(3); C99−Ru1−P2,

96.5(3); C99−Ru1−P3, 96.6(2); N1−Ru1−P3, 91.68(16); P1−Ru1−

P2, 122.67(7); P1−Ru1−P3, 118.20(8); P2−Ru1−P3, 116.42(9).

pronounced contraction of the Ru−N bond is observed:

2.184(2) Å (H,H-trans isomer) versus 2.0026(8) Å^10band

2.195(2) Å (H,H-syn isomer) versus 1.998(1) Å^10jfor the

parent and dehydrochlorinated complex, respectively].

When the same reaction was carried out with PPh₃instead of

PMe₃, the formation of a dark-red solution was observed. In the

¹H NMR spectrum, no signals were detected below 0 ppm,

whereas the ³¹P{¹H} NMR spectrum (81 MHz) showed two

signals, which appeared to be doublets of doublets at 57.7 and

52.9 ppm. Further NMR analysis proved the presence of one CO

ligand (δ_C= 217.7 ppm), whose IR frequency was determined to

be 1844 cm⁻¹. Eventually, the structure was clariﬁed by X-ray

crystallography (Figure 2; 6 in Scheme 2).

The complex does not resemble a ruthenium hydride

complex, and the formal oxidation state of the metal is 0. On

the one hand, it contrasts with the structure of 5, which is a

ruthenium hydride complex in the formal oxidation state 2+. On

the other hand, it shows a structure very similar to the previously

reported complex 3. In the solid state, the pentacoordinated Ru⁰

center adopts a distorted trigonal-bipyramidal geometry (with a

structural index parameter τ of 0.81²⁶). The CO ligand occupies

an axial position. The nitrogen atom of the PNP ligandstill

carrying the hydrogen atomis located trans to CO [N−Ru−

C, 178.24(7)°]. The two PPh₂side arms coordinate to

ruthenium in the equatorial position along with the PPh₃ligand.

The increased Ru−N distance [2.246(6) Å] compared to 5

[2.157(2) Å] can be rationalized by the lower oxidation state of

ruthenium in 6 and matches with the Ru−N distance in the

related Ru⁰complex 3 [2.25(1) Å¹⁸]. The same reasoning allows

one to understand the observed diﬀerences in the IR stretching

frequencies (3, 1851 cm⁻¹; 5, 1885 cm⁻¹; 6, 1844 cm⁻¹).

The conformation of PPh₃in 6 contrasts with the

conformation of PMe₃in 5: one of the C−P bonds of PPh₃is

oriented anti-periplanar to the carbonyl group [torsion angle

C71−P3−Ru1−C99, 165.5(4)°], while one of the C−P bonds

of PMe₃adopts a syn-periplanar conformation with CO [C8−

P3−Ru1−C99, 2.4(1)°]. Intuitively, the syn-periplanar con-

formation should be preferred because it places two of the

phosphines’ substituents in a less crowded space above the two

ethylene bridges of the PNP ligand rather than close to the

ligands’ phenyl groups. The opposite conformation in 6 places

one phenyl group fairly close above the NH functionality, and

the concerning Ru−P−C angle is strongly decreased compared

to the other two [Ru1−P3−C71, 113.8(3)°; Ru1−P3−C51,

120.9(3)°; Ru1−P3−C61, 121.5(2)°]. This structural feature

was also found in the quantum-chemical calculations (vide

infra). Therefore, a stabilizing N−H···π-phenyl interaction is

assumed to be one of the main reasons (along with packing

eﬀects and intramolecular dispersion interactions) for the

observed anti-periplanar conformation. It is concluded that

this interaction as well as the greater steric demand of PPh₃

compared to PMe₃leads to the preferred formation of the Ru⁰

complex 6 over its isomeric Ru^IIcounterpart, as is observed in

the case of PMe₃.

Other phosphorus-based ligands were also tested: P(OPh)₃

was also found to trap the “activated” Ru-MACHO but was also

prone to base-induced decompositions (Figure S1). The

sterically highly demanding P(tBu)₃did not to coordinate to

the ruthenium center because a complex mixture similar to that

in the reaction without any additional ligand was obtained

(Figures S7 −S10).

Reactions of 5 and 6 toward Alcohols and Esters.

Complexes 5 and 6 were tested as catalysts in (de)-

hydrogenation reactions to evaluate whether there is any

mechanistic diﬀerence of the Ru⁰versus Ru^IIcomplexes in the

active species. First, 5 was used in the catalytic (0.16 mol %)

dehydrogenative coupling of hexanol to hexyl hexanoate in

reﬂuxing toluene overnight. Under these unoptimized con-

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ditions, a quantitative conversion [determined by gas

chromatography (GC) and NMR spectroscopy] of the alcohol

to the ester was observed. The reaction could be reversed (>95%

GC/NMR yield) by transferring the reaction mixture under

argon directly to a Premex steel autoclave, pressurizing it with 60

bar of H₂, and heating it overnight at 130 °C (Scheme 3a).

Commercial hexyl hexanoate was hydrogenated under the same

unoptimized conditions (>99% GC/NMR yield) but only if it

was puriﬁed by distillation prior to its use.

detected at 5.36 ppm, which was assigned to the protonated

amide moiety. The protonation of 5 with MeOH is reversible

(Scheme 3b). Removal of all volatiles in vacuo and dissolution of

the solid in THF-d₈resulted in NMR spectra matching those of

complex 5. The addition of MeOH resulted again in the

formation of 7 (see Figure S15 for the corresponding NMR

spectra).

Because no crystals of 7 could be obtained, MeOH was

replaced by PhOH in the reaction with 5 (Scheme 3c). The

obtained onium complex 8 showed very similar spectroscopic

features in the NMR spectra compared to 7. Crystals of 8 could

be grown by layering a benzene solution with pentane at room

temperature, and its molecular structure was determined by X-

ray diﬀraction analysis (Figure 3). The geometric features of the

Scheme 3. Reactivity of Complex 5 toward Alcohols and

Esters: (a) Catalytic Dehydrogenation of Hexanol to Hexyl

Hexanoate Followed by Hydrogenation with H₂without Any

Work-up; (b) Reversible Protonation by MeOH; (c)

Protonation by PhOH

Figure 3. Molecular structure of 8 in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms and one

molecule of cocrystallized benzene are omitted for clarity. Selected

distances (Å) and angles (deg): Ru1−C99, 1.833(3); Ru1−N1,

2.194(2); Ru1−P1, 2.3152(8); Ru1−P2, 2.3233(8); Ru1−P3,

2.4170(7); Ru1−H1, 1.55(2); C99−Ru1−N1, 173.2(1); C99−Ru1−

P1, 95.06(9); C99−Ru1−P2, 97.76(9); C99−Ru1−P3, 95.17(9);

C99−Ru1−H1, 89.9(9); N1−Ru1−P3, 91.46(6); N1−Ru1−H1,

83.5(9); P1−Ru1−P2, 160.59(3); P1−Ru1−P3, 95.49(3); P2−

Ru1−P3, 97.80(3); P3−Ru1−H1, 175.0(9).

Similarly, complex 6 successfully converted hexanol into hexyl

hexanoate at a comparable catalyst loading (0.15 mol %) in

reﬂuxing toluene overnight. The hydrogenation with H₂of hexyl

hexanoate (0.13 mol % 6) proceeded equally well under the

previously mentioned conditions (>99% GC/NMR yield).

Because 5 and 6 were shown to catalyze (de)hydrogenation

reactions similarly well (see Figure S35 for the corresponding

kinetic data), the attention was turned to the question through

which the catalytic cycles of both complexes operate.

Stoichiometric NMR experiments were sought to understand

the initial steps of the catalytic process.

When isolated complex 5 was reacted with the simplest

alcohol, MeOH, at room temperature, an instant protonation of

5 was observed. The clean formation of complex 7 was suggested

by the ³¹P{¹H} NMR spectrum (81 MHz), which showed two

shifted doublets at +60.5 ppm (J = 18.3 Hz) and −26.6 ppm (J =

18.4 Hz) compared to the starting complex 5 (67.1 and −25.2

ppm). The characteristic doublet of triplets was detected in the

¹H NMR spectrum at −7.54 ppm (J = 86.9 and 18.9 Hz), slightly

downﬁeld from the hydride shift observed in 5 (−8.02 ppm).

The overall features of the spectral data are similar to those

observed for 5 with the exception that a new broad singlet was

cation of 8 are similar to those of its precursor (5): for example,

both exhibit an envelope conformation of the ﬁve-membered

metallacycles. Although all parameters are in a similar range, a

signiﬁcant eﬀect of the protonation at the ligands’ nitrogen is

observed [e.g., N1−Ru1−P3: 5, 88.52(4)°; 8, 91.46(6)° or

Ru1−N1: 5, 2.157(2) Å; 8, 2.194(2) Å]. The phenolate

counteranion of complex 8 is imbedded in a tight hydrogen-

bonding network with a molecule of PhOH [O50−O60,

2.557(4) Å] and a cocrystallized water molecule [O50−O1,

2.518(4) Å].²⁷The latter interacts with the NH functionality

[N1−O1, 2.938(4) Å]. The interactions clearly resemble the

ability of the NH group to attract polar groups, which is an

important feature in the mechanistic regimes presented in the

literature (for example, see ref 28) as well as in this work (vide

infra).

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Complex 7 did not serve as a competent catalyst for the

dehydrogenation of hexanol in reﬂuxing toluene, while complex

8 did. On the one hand, a complex mixture was obtained when

heating a sample of 7 in an NMR tube. It is suspected that the

ruthenium center is carbonylated and/or formylated, leading to

inactive species similar to those reported by Prakash and co-

workers on their work on basic MeOH dehydrogenation (see

the Supporting Information for a computational evaluation of

this process).^9hOn the other hand, phenolate 8 does not

decompose upon extended heating; therefore, the exchange with

hexanol is assumed to, consequently, furnish a productive

catalytic reaction.

In contrast, complex 6 and MeOH did not react at room

temperature. Upon heating, several species were observed by

³¹P{¹H} NMR spectroscopy, which looked similar to what was

observed for complex 7. Therefore, MeOH was replaced again

by PhOH as a surrogate alcohol. Now, a reaction occurred at

room temperature, although slowly overnight. In the corre-

1

sponding H NMR spectrum, a new triplet (J = 19.9 Hz) was

detected at −16.58 ppm. In the ³¹P{¹H} NMR spectrum, the

signals assigned to complex 6 had disappeared and two new

singlets were observed at 51.9 and −5.5 ppm. These data

suggested that a ruthenium hydride had formed and the PPh₃

ligand had dissociated from the metal center, maybe even being

substituted by the phenolate anion. Removing PPh₃from this

reaction mixture proved diﬃcult and, therefore, the hypothe-

sized product (9) was synthesized independently from Ru-

MACHO (1.0 equiv) through a salt metathesis with PhOK (1.0

equiv) in the presence of PhOH (1.0 equiv). The NMR data of 9

were in accordance with those obtained in the reaction of 6 and

PhOH. Crystals suitable for X-ray diﬀraction analysis were

obtained by layering a solution in THF with pentane, and the

molecular structure matches the ﬁndings in solution (Figure 4).

The PNP ligand arrangement around the metal is similar to 8

and exhibits an envelope conformation of the two ﬁve-

membered metallacycles. The phenolato oxygen atom and the

NH group engage in a hydrogen-bonding network with a

molecule of PhOH. This structural motif is known for two

diﬀerent alcohols and 1b: Gusev and co-workers reported it with

iPrO⁻/iPrOH (10)¹⁴and the Gauvin group with EtO⁻/EtOH

(11, Chart 1).^28cDespite the diﬀerent substituents on the

phosphorus and oxygen atoms, complex 9 is structurally very

similar to 10 and 11. The major diﬀerence of the CO ligand

being bent out of the equatorial plane in 9 is attributed to steric

eﬀects of the aryl versus alkyl substituents [N−Ru−C: 9,

167.4(2)°; 10, 175.2(3)°; 11, 178.09(9)°]. The distances in the

hydrogen-bonding network cover a similar range [N−O: 9,

2.994(5) Å; 10, 2.864(9) Å; 11, 2.932(3) Å; O−O: 9, 2.523(5)

Å; 10, 2.494(7) Å; 11, 2.495(3) Å].

Figure 4. Molecular structure of 9 in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms and one

molecule of cocrystallized THF are omitted for clarity. Selected

distances (Å) and angles (deg): Ru1−C99, 1.811(4); Ru1−N1,

2.200(3); Ru1−O50, 2.234(3); Ru1−P1, 2.310(2); Ru1−P2,

2.328(2); Ru1−H1, 1.50(4); C99−Ru1−N1, 167.39(16); C99−

Ru1−O50, 108.0(2); C99−Ru1−P1, 93.9(2); C99−Ru1−P2,

99.3(2); C99−Ru1−H1, 86(2); N1−Ru1−O50, 84.5(2); N1−Ru1−

H1, 81(2); O50−Ru1−P1, 95.33(9); O50−Ru1−P2, 90.54(9); P1−

Ru1−P2, 163.24(4); O50−Ru1−H1, 165(2).

Chart 1. Ruthenium(II) Hydride Alcoholato Complexes with

an Aliphatic PNP Ligand

them as a resting state of dehydrochlorinated 1b.^28cBecause

they presented detailed experimental work on the involved steps

as well as on the formation of deactivation species (vide infra), it

is assumed that 5 and 6 lead to similar catalytic cycles.

It is important to note that the alcohol oxidatively adds in a

trans disposition to the Ru⁰center of 6, forming a Ru^II

complex.²⁹⁻³¹The same 0/2+ oxidation on ruthenium was

observed by us with the Ru⁰complex 3.¹⁸When 8 and 9 are

compared, complex 8 resembles a precursor to 9, in which the

transformation 8 → 9 is only precluded by the tight binding of

PMe₃to the ruthenium center.

Finally, complex 9 was shown to serve as an excellent base-free

catalyst in the dehydrogenation of hexanol (0.11 mol %,

reﬂuxing toluene overnight, full conversion, and quantitative

yield by GC and NMR).

Computational Investigations. The next step was to

endeavor computational methods (see the Supporting In-

formation for details), ﬁrst, to rationalize the formation of Ru^II

complex 5 and Ru⁰complex 6 and, second, to evaluate in which

mechanistic scenarios each of the two complexes is involved.

Due to the extensive interest in pincer-type catalysts for

hydrogenation/dehydrogenative coupling, a variety of groups

have previously performed experimental and theoretical studies

on the underlying mechanisms: Beller and co-workers published

a detailed investigation on complex 1b,^10jand Chen et al.

studied Gusev’s Ru-SNS complex.³²Computational investiga-

tions were also conducted for Milstein’s Ru^II-PNN^28aand other

related chiral pincer complexes.^28b,33We are only aware of two

computational studies employing the full Ru-MACHO complex

Complexes 5 and 6 have been shown to lead to closely related

species upon reaction with alcohols. The Gauvin group has

isolated a similar species (11) derived from 1b and assigned

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Scheme 4. (a) Comparison of the Ru⁰and Ru^IIStabilities for PMe₃, (b) Comparison of the Ru⁰and Ru^IIStabilities for PPh₃, (c)

Formation of the Phenolato Complex 8-iso_calcand Onium Complex 8_calcfrom 5_calc, and (d) Formation of the Phenolato Complex

a

9_calcand Onium Complexes 9-iso_calcfrom 6_calc

a

Experimentally observed structures are highlighted with blue dotted lines. ΔG²⁹⁸in kJ mol⁻¹; RI-PBE0-D3(BJ)/def2-QZVPP//BP86/def2-SV(P);

COSMO-RS (toluene).

(i.e., no simpliﬁcations in the structural complexity for the

purpose of reducing computational costs).³⁴First, Jiang et al.

studied the mechanism of MeOH-to-carbonate dehydrogen-

ation. However, MeOH is a very small substrate that has been

shown to diﬀer signiﬁcantly from larger substrates in terms of

interactions with the Ru-PNP fragment.^9e,35Second, a very

recent report by Kaithal et al. on the mechanism of β-

methylation of alcohols involves several steps of the Dub-type

pathway (vide infra) without any detailed discussion of other

mechanistic scenarios, relevant resting states, or the related

literature.^34bIn this context, we wanted to address some speciﬁc

aspects that were not considered in detail so far: (1) the resting

state of the catalyst, (2) the role of the HN(CH₂CH₂PPh₂)₂

ligand and the alcohol substrate, (3) an investigation of all

possible reaction pathways, (4) the potential inﬂuence of the

oxidation state (Ru⁰versus Ru^II), and (5) the speciﬁc role of the

NH function.

Rationalization of the Observed Chemoselectivities.

To gain a deeper understanding of the underlying principles, the

experimentally observed ruthenium species and their stoichio-

metric reactions with alcohols were investigated initially. First,

the chosen quantum-chemical approach was validated by

comparing the calculated structures of 5 and 6 with their

molecular structures in the solid state (Tables S4 −S7). The Ru^II

complex 5_calcis found to be signiﬁcantly more stable than the

isomeric Ru⁰complex (5-iso_calc; ΔG²⁹⁸= 10.2 kJ mol⁻¹; Scheme

4a), while the computed relative energies of the PPh₃

counterparts (6_calcand 6-iso_calc) indicate an endergonic Ru⁰-

to-Ru^IIisomerization (ΔG²⁹⁸= 28.8 kJ mol⁻¹; Scheme 4b).

Multiple contributions can be described that lead to a diﬀerence

in the observed products when employing PMe₃or PPh₃. First,

the change from an octahedral to a trigonal-bipyramidal

coordination geometry leads to a signiﬁcant steric relaxation.

Second, the more electron-rich Ru⁰motif is favored by less

electron-rich phosphine [Tolman electronic parameter: 2064

cm⁻¹(PMe₃) and 2069 cm⁻¹(PPh₃)].³⁶Third, 6_calcexhibits an

N−H···π-phenyl interaction (Ru1−P3−C71, 111.8°), which

was also identiﬁed in the crystal structure [Ru1−P3−C71,

113.8(3)°] and increases the stability of this isomer (vide supra).

Next, the experimentally observed diﬀerence in the reactivity

of 5 and 6 toward PhOH was probed by calculating the

corresponding phenolato (8-iso_calcand 9_calc, respectively) and

onium (8_calcand 9-iso_calc, respectively; Scheme 4c,d) complexes.

The calculations show that protonation of 5_calcleads to the very

stable onium complex 8_calc(ΔG²⁹⁸= −40.4 kJ mol⁻¹), which is

not prone to PMe₃substitution through PhO⁻, because this

would lead to a species of higher relative energy (8-iso_calc; ΔG²⁹⁸

= 11.1 kJ mol⁻¹; Scheme 4c). Once more, the reactivity changes

when PPh₃is employed: a more stable ruthenium(II) phenolato

complex is observed (Scheme 4d; 9_calc, ΔG²⁹⁸= 8.1 kJ mol⁻¹; 9-

iso_calc, ΔG²⁹⁸= 10.0 kJ mol⁻¹). Although the diﬀerence in free

energy between 9_calcand 9-iso_calc(ΔΔG²⁹⁸= 1.9 kJ mol⁻¹) is far

much smaller than that between 8-iso_calcand 8_calc(ΔΔG²⁹⁸

=

51.5 kJ mol⁻¹), it should be noted that the free-energy diﬀerence

will increase because of the entropically unfavored phenolate

complex 9-iso_calcat higher reaction temperatures. A loss in

entropy would be expected because of the conversion of two

molecules (5_calc+ PhOH or 6_calc+ PhOH) to a tightly coupled

ion pair (8_calcor 9-iso_calc, respectively) rather than in the

formation of 8-iso_calcor 9_calc, in which the number of molecules

remains unchanged. Similar to the discussed energetic diﬀer-

ences of 5 and 6, the inverted stability is attributed to the

diﬀerent substituents of the phosphine ligands. The onium

complex will be preferred if the PR₃ligand is not too sterically

demanding. This renders the octahedral coordination environ-

ment, in which PR₃is bound to the Ru center, more feasible, and

provides additional space for a stabilizing hydrogen bond

between the alcoholate anion and the complex. The higher steric

demand of PPh₃does not favor the structure of 9-iso_calcbut

rather PPh₃substitution by the phenolate becomes preferred

(Scheme 4d). This also oﬀers an explanation for the observed

energy diﬀerence between 8_calcand 9-iso_calc(ΔΔG²⁹⁸= 50.4 kJ

mol⁻¹) in contrast to the small diﬀerence in energy of formation

between 8-iso_calcand 9_calc(ΔΔG²⁹⁸= 3.0 kJ mol⁻¹).

Computational Investigation of the Reaction Mecha-

nism. Complexes 5 and 6 have been shown to lead to closely

related species upon reaction with alcohols. Therefore, the

possibility of diﬀerent mechanistic scenarios for each of the

complexes was investigated. The literature is coined by the

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Scheme 5. Catalytic Cycles for the Dehydrogenation of Ethanol to Ethanal Catalyzed by a Ru-PNP Complex Analogously to the

Proposed Mechanisms by (a) Noyori et al. and (b) Dub et al.

Scheme 6. Noyori- (Black) and Dub-Type (Blue) Lowest-Energy Pathways for the Dehydrogenation of Ethanol to Ethanal with

a

Complex A (i.e., 5)

a

Mass balance for additional stabilizing substrate equivalents is ensured in the entire scheme. ΔG³⁸³in kJ mol⁻¹; RI-PBE0-D3(BJ)/def2-QZVPP//

BP86/def2-SV(P); COSMO-RS (toluene).

Noyori-type catalytic cycle (Scheme 5a), which enables

(de)hydrogenation via metal−ligand cooperation

(MLC).^28a,37More recently, Dub et al.^28a,33,38as well as

others^4c,39have proposed a revised mechanism, which does not

involve MLC (i.e., cleavage and formation of the N−H bond)

but rather a metal−ligand-assisted (MLA) pathway, in which

N−H cleavage does not occur (Scheme 5b). In addition to these

well-established mechanistic regimes, our computational

investigations also included other mechanistic scenarios, of

which some ﬁnd precedence in the literature (see the Supporting

G

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Scheme 7. Tishchenko-like Pathway Directly Generating Ethyl Acetate from Ethanol and Ethanal (Black) and Formation of

a

Intermediary Hemiacetal for Further Dehydrogenation to the Desired Ester (Blue)

a

The fate of complex G (e.g., how it can be converted to complex M) is discussed in detail in the Supporting Information. Mass balance for

additional stabilizing substrate equivalents is ensured in the entire scheme. ΔG³⁸³in kJ mol⁻¹; RI-PBE0-D3(BJ)/def2-QZVPP//BP86/def2-SV(P);

COSMO-RS (toluene).

Information).⁴⁰For all computed catalytic cycles, ethanol was

employed as a substrate, which was also shown to be converted

to ethyl acetate (see the Supporting Information). The

application of Noyori’s mechanism to the Ru-MACHO system

leads to a cycle that proceeds from the conventionally proposed

dehydrochlorinated Ru-MACHO (1_Noyori) via a concerted

proton hydride transfer (TS-2_Noyori) and the aldehyde adduct

3_Noyorito the dihydride complex 4_Noyori(Scheme 5a). This

species undergoes an alcohol-assisted proton shuﬄe (TS-

Therefore, only the catalytic cycles involving complex 5_calcare

discussed here (the analogous discussion for complex 6_calcis

provided in the Supporting Information). Starting from the Ru^II-

PMe₃complex (A), phosphine dissociation is endergonic

(ΔG³⁸³= 45.8 kJ mol⁻¹) and contributing signiﬁcantly to the

overall activation barrier. A cascade of proton (TS-C; ΔG^⧧=

65.6 kJ mol⁻¹) and hydride (TS-E; ΔG^⧧= 74.7 kJ mol⁻¹)

transfers leads to G, which resembles the ethanol-stabilized

equivalent of the dihydride complex 4_Noyori(cf. Scheme 5a).

Proton shuﬄe via TS-H (ΔG^⧧= 110.4 kJ mol⁻¹) leads to the

dihydrogen complex I (ΔG³⁸³= 92.2 kJ mol⁻¹), which

regenerates the “activated” complex B (ΔG³⁸³= 47.5 kJ

mol⁻¹) after H₂liberation and closes the Noyori-type cycle

(cf. Scheme 5a). In contrast, the Dub-type pathway starts from

dihydride complex G and results in complex K (ΔG³⁸³= 87.5 kJ

mol⁻¹) via proton transfer in TS-J (ΔΔG³⁸³= 93.3 kJ mol⁻¹).

Subsequent dihydrogen dissociation gives L (ΔG³⁸³= 86.4 kJ

mol⁻¹), and a highly exergonic formation of a C−H···Ru

interaction leads to D (ΔG³⁸³= 47.9 kJ mol⁻¹). Complex D

liberates the product ethanal and regenerates the dihydride

species G via an ethanol-assisted hydride transfer TS-E (ΔG^⧧=

76.4 kJ mol⁻¹).

5_Noyori), which yields the ruthenium dihydrogen complex 6_Noyori,

which subsequently liberates H₂to regenerate 1_Noyori. The

proton shuﬄing step is sometimes described as a direct proton

transfer from the NH function to the metal center. However,

calculations show that the explicit involvement of alcohol

drastically lowers the activation barrier.^28d,32In contrast,

applying Dub’s mechanism to the Ru-MACHO system results

in a diﬀerent catalytic cycle: starting from the common species of

both cycles, the ruthenium dihydride complex 1_Dub, a proton

transfer from ethanol (TS-2_Dub) will yield complex 3_Dub, which

subsequently liberates H₂to form complex 4_Dub. The formation

of an intramolecular C−H···Ru interaction (5_Dub) sets the stage

for a hydride transfer (TS-6_Dub), ultimately leading to ethanal

In conclusion, the Dub-type MLA cycle was calculated to be

signiﬁcantly more favored over the Noyori-type metal−ligand

cooperative process (ΔΔG^⧧= 17.1 kJ mol⁻¹). The rate-

determining step in the Noyori- and Dub-type pathways is

generation of the ruthenium dihydrogen complexes I (via TS-

H) and K (via TS-J), respectively. However, because the

ruthenium dihydride complex G must be formed from the

resting state A, the initial sequence A → B → D → F → G of the

Noyori-type cycle will be required to form the on-cycle species

G for the Dub-type pathway. All alternative mechanisms

and the dihydride complex 1_Dub

.

Although many mechanistic scenarios were evaluated in this

study, our computational studies did not result in any feasible

mechanistic regime in which the PR₃ligand stays coordinated to

the metal (see Scheme S6 for details). Therefore, the only

energetic diﬀerence between 5 and 6 results from the relative

energy of the “activated” complex 1_Noyorito the resting states,

5

_calcand 6_calc. The dissociation of PMe₃in 5_calc(ΔG³⁸³= 45.8 kJ

mol⁻¹) is 3.0 kJ mol⁻¹less favorable than the generation of B

(Scheme 6; cf. 1_Noyori) from 6_calc(ΔG³⁸³= 42.8 kJ mol⁻¹).

H

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investigated during this study show higher Gibbs free energies of

activation compared to the reaction pathways discussed above

(Scheme 6). Only one catalytic cycle based on the work by

Hasanayn et al.^40aposes an alternative way to generate the

ruthenium dihydride complex G via a “slippage” of the

alcoholato ligand and is quite competitive to the Noyori-type

pathway (ΔΔG^⧧= 5.5 kJ mol⁻¹; cf. Scheme S5). Although the

activation barrier of the “slippage” mechanism is higher for our

system, this could be a viable pathway for the formation of an on-

cycle species of the energetically favored Dub-type cycle and

should be considered in the investigation of similar systems.

For the Dub-type cycle, the resting state A can again be

accessed through the sequence D → B → A (i.e., to the reverse

sequence in the Noyori-type cycle) because the barrier of TS-C

(ΔG^⧧= 65.6 kJ mol⁻¹; Scheme 6) is far more feasible than

regenerating the dehydrochlorinated Ru-MACHO (B) directly

from the dihydride complex G (via TS-H; ΔG^⧧= 110.4 kJ

mol⁻¹).

Probing the Catalysts’ Stabilities. As shown in the

previous section, Ru-MACHO (1a)/base, 5, and 6 serve as

precatalysts for the same catalytic cycle after activation (i.e.,

base-induced HCl abstraction or PR₃dissociation/substitu-

tion). Because the initial goal of this work was to stabilize the

“activated” Ru-MACHO (2) and prevent its decomposition, the

next step was to test whether complexes 5 and 6 show a stability

advantage over the Ru-MACHO/base system. Because 5 and 6

showed essentially the same catalytic performance, the focus in

these experiments was put on complex 6 with its PPh₃ligand

because PPh₃is much easier to handle on both a laboratory and

an industrial scale: PPh₃is an odorless and cheap bulk chemical

as opposed to the much more expensive, air-sensitive, and toxic

PMe₃with its strongly unpleasant odor, which would be

especially of relevance in the synthesis of esters used as

fragrances.

It was noticed early in this study that the gas chromatograms

of the reaction mixtures looked quite diﬀerent depending on the

catalytic system employed (see the Supporting Information): in

the case of Ru-MACHO (1a) and KOtBu (a 100-fold excess

with respect to 1a was used; this typical Ru-MACHO/base ratio

was used in many other reports), several other unassigned

signals besides the expected ones for solvents, tBuOH (from the

base KOtBu), and the ester product were detected (Figure S30).

A much cleaner gas chromatogram was obtained in the reaction

catalyzed by 6 (Figure S31). In line with the previous

observation that Ru-MACHO (1a) can be decomposed in the

presence of strong bases (cf. Scheme 1), it is suggested that the

additional signals in the gas chromatogram belong to species

formed by catalyst degradation and/or unwanted side reactions.

A similar observation was made when complex 6 was employed

in a catalytic dehydrogenation in the presence of a 100-fold

excess of KOtBu (Figure S32). This ﬁnding is further supported

by the positive-ion electrospray ionization (ESI+) mass spectra

of the three reaction mixtures after completion and removal of

all volatiles in vacuo (Figure 5). The mass spectrum of the

reaction catalyzed by 6 shows essentially only one major signal

(m/z 832.1606), which is assigned to the [6 − H]⁺ion (Figure

5a; see also Figure S36 for the isotope pattern). In contrast, the

mass spectrum of the reaction catalyzed by Ru-MACHO (1a)/

KOtBu shows no signal for the dehydrochlorinated Ru-

MACHO, which is usually observed as [2 + H]⁺(m/z

572.08).^17,18Instead, several signals in the mass range m/z

700−1200 were detected that cannot be assigned to any

plausible structures at the moment (Figure 5b). It shows a

pattern similar to that of the spectrum recorded of the base-

induced, but substrate-free, decomposition of Ru-MACHO (1a,

Figure S35). The reaction catalyzed by 6 with an excess of

KOtBu gave a mass spectrum with multiple signals (range: m/z

700−1200) of which one (m/z 832.1606) matched again the

expected mass of the [6 − H]⁺ion (Figure 5c). In addition, the

in situ generation of 6 was also investigated by employing

catalytic amounts of Ru-MACHO (1a, 1.0 equiv), KOtBu (1.0

equiv), and PPh₃(3.0 equiv). The results of mass spectrometric

analyses are similar to those obtained with isolated complex 6

(Figures S37 and S38), proving that isolation of the stabilized

dehydrochlorinated Ru-MACHO is not a requirement to obtain

a catalytically active system with an improved stability.

Furthermore, the original in the Noyori-type cycle proposing

concerted proton hydride transfer (TS-2_Noyori; Scheme 5a)

could not be located.^37aA stepwise pathway B → F via TS-C, D,

and TS-E (Scheme 6) will perform the same transformation at a

feasible activation barrier (ΔG^⧧= 74.7 kJ mol⁻¹). This

phenomenon has been discussed previously and was attributed

to the choice of solvent modeling.^10j,28aMoreover, Dub et al.

highlighted that there is a signiﬁcant diﬀerence in the calculated

energies depending on their choice of solvent modeling.^28a

A

similar observation was made when looking at stabilization of

the rate-determining steps (TS-J and TS-H) by one or two

additional substrate molecules. The use of explicit ethanol

stabilization, which means to speciﬁcally calculate the system

with the ethanol molecules rather than just using COSMO-RS

or a similar approximation method, always leads to the MLA

pathway (TS-J). In particular, this transition state could not be

characterized without such interactions, while TS-H could only

be located without including any further substrate molecules in

the calculations. This agrees with the chemical intuition that

stabilization of the anionic fragment would signiﬁcantly decrease

its tendency to abstract the N−H proton.

After alcohol dehydrogenation to an aldehyde, two diﬀerent

pathways for ester formation will compete:^28bOn the one hand,

a Tishchenko-like coupling of one molecule of each, alcohol and

aldehyde, at the metal center to the ester could occur. On the

other hand, intermediary hemiacetal formation in combination

with a second dehydrogenation step would also yield the ester

product (Scheme 7). Each of these pathways have been

previously suggested to take part in these types of

reactions.^2a,28b,cBoth share the initial transition state TS-N to

form species O (ΔG³⁸³= 63.6 kJ mol⁻¹) from the ethanolato

complex M (ΔG³⁸³= 39.6 kJ mol⁻¹) via an activation barrier of

99.9 kJ mol⁻¹. Hydride transfer (TS-P) will break down complex

O into the dihydride complex G and ethyl acetate (ΔG^⧧= 79.3

kJ mol⁻¹). On the contrary, TS-Q would transform complex O

to the hemiacetal adduct R. This as well as a one-step

transformation from O to B could not be located. Geometry

optimizations repeatedly led back to complex O, indicating that

these are higher in energy. Last, the transition state for the metal-

free hemiacetal formation was calculated and found to be

kinetically disfavored (ΔG^⧧= 110.8 kJ mol⁻¹; Scheme S11).

Consequently, the observations indicate that the ester is directly

formed on the metal complex without the hemiacetal being

released as an intermediate.

The avoided decomposition of the “activated” Ru-MACHO

(2) in the presence of PPh₃was expected to be reﬂected in the

turnover numbers (TONs) of the two catalytic systems. To test

this, dehydrogenative coupling reactions were conducted with

puriﬁed hexanol and toluene at low catalyst loadings with a 1:1

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Figure 6. Column plot of the initial rates (−k) of three consecutive

dehydrogenative couplings of hexanol catalyzed by Ru-MACHO (1a)/

KOtBu (red) and complex 6 (blue).

KOtBu in the third batch (−k₃in 10⁻⁵s⁻¹: 1a/KOtBu, 12.6

0.9; 6, 22 2). These data, together with the MS measurements,

are believed to exemplify that an appreciable stability advantage

of the Ru-MACHO/base system can be achieved upon the

addition of a phosphine. Consequently, further studies are

required to render this approach applicable.

In summary, these experiments show that 1 equiv of base is

suﬃcient to generate 2, while higher base loadings degrade the

catalyst (cf. Figures 5c and S38). The catalyst is active as long as

a substrate is available and suﬀers from deactivation the longer it

is left without a suitable substrate. This can be opposed by

adding a stabilizer (e.g., PPh₃) to the reaction mixture or using

the stabilized “activated” Ru-MACHO (i.e., complexes 5 or 6)

directly if base-free conditions are necessary.

Figure 5. ESI+ mass spectra (mass range: m/z 200−2000) recorded

after the evaporation of all volatiles in vacuo. Reaction conditions (all 5

mmol of hexanol in reﬂuxing toluene overnight): (a) 0.12 mol % 6; (b)

0.14 mol % Ru-MACHO (1a) and 10 mol % KOtBu; (c) 0.13 mol % 6

and 10 mol % KOtBu.

ratio of Ru-MACHO (1a) and KOtBu with and without a 13-

fold excess of PPh₃. At S/C = 32500, a 37% conversion (>99%

selectivity) of the alcohol to the ester was obtained for both

catalytic systems. This corresponds to a TON of 12000 and is in

the range of what is reported in the literature (note that, for

example, the reported TON of 15400 was obtained at a 1a-to-

base ratio of 1:120^6b). This indicates that, as long as enough

substrate is available, the catalytic system cannot beneﬁt from

the stabilizing eﬀect of the phosphine. Therefore, this eﬀect

should be observed in batchwise reactions, where the catalyst is

recycled. Because such a recycling is challenging for an air-

sensitive, homogeneous catalyst on a laboratory scale, we

decided to measure the initial rate kinetics of three consecutive

dehydrogenations as a sensitive probe for catalyst deactivation.⁴¹

In this catalyst recycling experiment, a batch of hexanol (10

mmol; S/C = 670) was added to the reﬂuxing reaction mixture

after 3 and 6 h (see the Supporting Information for experimental

details). Here, it is important that the ﬁrst batch of hexanol was

already fully consumed after less than 1 h for each of the catalytic

systems [Ru-MACHO/KOtBu (1:1) and 6]. Hence, the

catalysts were left without substrate for >2 h at 110 °C. In the

ﬁrst batch, the rate of the Ru-MACHO/base system [−k₁(1a/

KOtBu) = (130 20) × 10^{−5 s−1}] and the rate for complex 6

Role of the Base in Reactivating Deactivated Cata-

lysts. It is unquestionable that only 1 equiv of base is necessary

to dehydrochlorinate Ru-MACHO and its derivatives (1a−1c)

to generate the activated catalyst 2. Contrary to that, a brief look

at the literature reveals that a large (i.e., up to a 100-fold) excess

of base is usually employed in (de)hydrogenation reactions. As

was shown, this excess leads to catalyst degradation, and only 1

equiv of base with respect to the catalyst is required if high-grade

materials are used. Nguyen et al. have reported that one main

deactivation pathway of 1b occurs through traces of water,

giving rise to catalytically inactive ruthenium carboxylate

complexes, which have been shown to be reactivated by base.^28c

In the aforementioned dehydrogenative coupling of hexanol

at low catalyst loadings (previous section), it was found that

supplementing catalyst 6 with an equimolar amount of KOtBu

improved the reaction outcome signiﬁcantly (S/C = 32200, 49%

conversion, TON = 16000). Even though great care was taken in

the puriﬁcation of the starting materials, small amounts of

impurities seem to have a major impact on the reaction outcome.

Consequently, accurate comparisons between diﬀerent systems

can only be made if the amount of base is kept constant.

Brieﬂy, the nature of deactivation species derived from 5 and 6

was also investigated. Benzoic acid was chosen as an archetypical

deactivating agent and reacted in a 1:1 molar ratio with 5 as well

as 6. The former was simply protonated at the amido nitrogen

(Scheme 8), and the resulting onium complex 12 resembles

spectroscopic and structural features very similar to those

described earlier for complex 8 (Figure 7). The complex’

[−k₁(6) = (113

7) × 10^{−5 s−1}] are the same within the

experimental error. The preservation of the initial rates in the

second and third batches with respect to the ﬁrst batch was ca.

15% and 10% for 1a/KOtBu and ca. 37% and 19% for 6 (Figure

6). This is a drastic drop in activity for both systems; however,

the stabilized complex 6 exhibits almost the doubled rate of 1a/

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Scheme 8. Reactions of 5 and 6 with Benzoic Acid

Figure 8. Molecular structure of 13a in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms are omitted

for clarity. Selected distances (Å) and angles (deg): Ru1−C99,

1.841(3); Ru1−N1, 2.184(2); Ru1−O51, 2.231(2); Ru1−P1,

2.3242(6); Ru1−P2, 2.3014(6); Ru1−H1, 1.57(2); C99−Ru1−N1,

174.2(1); C99−Ru1−O51, 96.71(9); C99−Ru1−P1, 100.34(8);

C99−Ru1−P2, 94.53(8); C99−Ru1−H1, 88.0(8); N1−Ru1−O51,

88.45(8); N1−Ru1−H1, 87.0(8); O51−Ru1−P1, 94.31(5); O51−

Ru1−P2, 90.87(5); P1−Ru1−P2, 163.55(2); O51−Ru1−H1,

175.0(9).

complexes derived from 1b very well (14^10jand 15,^28c

respectively; Chart 2).

Chart 2. Structurally Described Literature-Known

Complexes Related to 13a and 13b

Figure 7. Molecular structure of 12 in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms are omitted

for clarity. Selected distances (Å) and angles (deg): Ru1−C99,

1.832(5); Ru1−N1, 2.193(4); Ru1−P1, 2.318(2); Ru1−P2, 2.327(2);

Ru1−P3, 2.436(2); Ru1−H1, 1.69(4); C99−Ru1−N1, 172.9(2);

C99−Ru1−P1, 95.7(2); C99−Ru1−P2, 97.2(2); C99−Ru1−P3,

95.9(2); C99−Ru1−H1, 89(2); N1−Ru1−P3, 91.2(2); N1−Ru1−

H1; 84(2); P1−Ru1−P2, 160.05(5); P1−Ru1−P3, 97.04(5); P2−

Ru1−P3, 96.73(4); P3−Ru1−H1, 175(2).

benzoate counteranion interacts with the NH functionality of

the onium complex and a cocrystallized molecule of benzoic acid

through hydrogen bonding [N1−O50, 3.272(5) Å; N1−O51,

3.062(5) Å; O51−O61, 2.506(5) Å].

Structure determination from the colorless planks, however,

revealed a conformational polymorph of 13 with two

independent molecules in the asymmetric unit (Figure 9; only

one independent molecule is depicted). In the molecular

structure, the hydride and NH hydrogen exhibit a cis

orientation. Consequently, the envelope conformation of the

two ﬁve-membered metallacycles is inverted compared to 13a.

Most obvious is the conformational diﬀerence around the Ru−

O bond, which is syn-periplanar to the CO group rather than

anti-periplanar as 13a is [13a, C99−Ru1−O51−C50,

168.1(2)°; 13b, C99−Ru1−O51−C50, 1.7(5)°, 2.4(5)°].

This conformation is only possible because the two independent

molecules engage in an intermolecular hydrogen bond between

the carbonyl oxygen and the NH hydrogen [N1−O50, 2.913(7)

and 2.897(7) Å]. This leads to a polymeric chain throughout the

crystal lattice (Figure S2). This structural feature has not been

reported in the literature for these types of complexes. The most

similar complex 16 (Chart 2) adopts the same syn-periplanar

The latter (6), in contrast, exhibited reactivity toward benzoic

acid similar to that observed toward PhOH earlier (vide supra).

The Ru⁰center is protonated [δ_H= −17.00 ppm (t, J = 19.7

−

Hz)] and PhCO₂substitutes the PPh₃ligand [δ_P= 55.3 (s),

−5.5 (s) ppm] to furnish complex 13 (Scheme 8). Crystals

suitable for X-ray diﬀraction analysis were grown by layering the

NMR sample with pentane. Colorless crystals of two habits

(some appeared as plates and others as planks) were found in the

sample, and both were measured on the diﬀractometer. The

colorless plates resulted in the expected structure of 13 (13a,

Figure 8). The benzoate trans to the hydride H1 bridges the

ruthenium center and the NH functionality via a hydrogen bond

[N1−O50, 1.256(3) Å]. The spectroscopic and structural data

match those of the literature-known formate and acetate

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Scheme 9. Reactions toward Other Ru⁰Complexes Derived

from the Methylated Ru-MACHO (17)

crystals from the NMR experiment with PMe₃by layering the

NMR sample with pentane (Figure 10). Indeed, the molecular

Figure 9. Molecular structure of 13b in the solid state with ellipsoids

depicted at the 50% probability level. C−H hydrogen atoms, the second

independent molecule, and three molecules of cocrystallized THF are

omitted for clarity. Selected distances (Å) and angles (deg): Ru1−C99,

1.815(6); Ru1−O51, 2.184(4); Ru1−N1, 2.195(5); Ru1−P2,

2.309(2); Ru1−P1, 2.311(2); Ru1−H1, 1.59(6); C99−Ru1−N1,

175.0(2); C99−Ru1−O51, 101.7(2); C99−Ru1−P1, 98.5(2); C99−

Ru1−P2, 97.3(2); C99−Ru1−H1, 81(2); N1−Ru1−O51, 83.1(2);

N1−Ru1−H1, 94(2); O51−Ru1−P1, 97.2(2); O51−Ru1−P2,

86.4(2); P1−Ru1−P2, 162.68(6); O51−Ru1−H1, 177(2).

conformation [C−Ru−O−C, 2.6(2)°] but cannot form the

polymeric chains because the NH group is replaced by an NMe

group.^16bAccordingly, the conformation of 16 is believed to be a

result of the smaller steric clash between the acetate and NMe

group.

Figure 10. Molecular structure of 18 in the solid state with ellipsoids

depicted at the 50% probability level. Hydrogen atoms and disordered

ethylene bridges are omitted for clarity. Selected distances (Å) and

angles (deg): Ru1−C99, 1.860(2); Ru1−N1, 2.262(2); Ru1−P1,

2.2895(4); Ru1−P2, 2.3127(4); Ru1−P3, 2.2566(5); C99−Ru1−N1,

92.85(7); C99−Ru1−P1, 113.73(5); C99−Ru1−P2, 125.24(5);

C99−Ru1−P3, 87.56(6); N1−Ru1−P3, 179.06(4); P1−Ru1−P2,

119.77(2); P1−Ru1−P3, 95.695(15); P2−Ru1−P3, 97.78(2).

It was not surprising to ﬁnd that both 12 and 13 did not lead

to any ester formation in the catalytic dehydrogenation of

hexanol. When a 3-fold excess of KOtBu (with respect to the

catalysts) was added to the mixtures, the reaction proceeded

smoothly at high conversions (>99%) and selectivities (>95%).

Attempts to Synthesize Other Ru⁰-PNP Complexes.

Looking at complex 6, one might wonder if other Ru⁰complexes

bearing the aliphatic PNP ligand scaﬀold are accessible. Some

preliminary experiments were conducted with the methylated

Ru-MACHO complex 17,^9aalthough knowing that it will

probably not furnish competent (pre)catalysts for (de)-

hydrogenation reactions. Similar to the synthetic routes of 5

and 6 (vide supra), 17 was reacted with KOtBu in the presence

of PMe₃and PPh₃in two separate NMR experiments (Scheme

9). In both experiments, no signals were observed below 0 ppm

structure conﬁrms the assumed formation of a pentacoordinated

Ru⁰complex (τ = 0.90²⁶). While the PNP pincer ligand arranges

in a comparable fashion around the metal center as in 6, the

positions of CO and phosphine are interchanged. Here, PMe₃is

located trans to the amine nitrogen [N1−Ru1−P3, 179.06(4)°],

and CO is bound in the equatorial position next to the

phosphine side arms [P1−Ru1−C99,113.73(5)°; P2−Ru1−

C99,125.24(5)°]. As far as the literature is concerned, it seems

that this is the ﬁrst example of a Ru⁰-PNP complex, bearing a

phosphine and a CO in this conﬁguration. The closest

representatives are, in fact, complexes 3 and 6, whose trigonal-

bipyramidal geometry features the trans arrangement of the

ligands’ nitrogen and CO [Ru−N distances: 3, 2.25(1) Å; 6,

2.246(6) Å; 18, 2.262(2) Å].

1

in the H NMR spectra. In the ³¹P{¹H} NMR spectra of the

reaction with PMe₃, a doublet (53.9 ppm, J = 32.9 Hz) and a

triplet (23.6 ppm, J = 32.9 Hz) were detected, while the

spectrum of the reaction with PPh₃showed two apparent

doublet of doublets (54.8 and 47.2 ppm), similar to those found

in the formation of 6 (vide supra). Both experiments suggested

the formation of the anticipated Ru⁰complexes 18 and 19

(Scheme 9).

The ﬁrst catalytic experiments with 18 (75% purity by

³¹P{¹H} NMR spectroscopy) and in situ generated 19 did not

show any signiﬁcant conversion in the dehydrogenative coupling

Unfortunately, the reactions turned out to be sluggish, and

dedicated syntheses to obtain clean material for further studies

have not been successful yet. However, it was possible to obtain

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of hexanol. This agrees with the literature and our calculations:

the presence of the NH group is the important feature to obtain

an eﬀective catalyst, and the nature of the Ru⁰center does not

change the operating mechanism.

AUTHOR INFORMATION

■

Corresponding Author

Thomas Schaub − Catalysis Research Laboratory (CaRLa), D-

69120 Heidelberg, Germany; BASF SE, Organic Synthesis, D-

67056 Ludwigshafen, Germany; orcid.org/0000-0003-

2332-0376; Email: thomas.schaub@basf.com

SUMMARY AND CONCLUSION

■

This work shows that the previously reported degradation of Ru-

MACHO (1a) by a base can be prevented to a certain extent by

adding a phosphine, which stabilizes the “activated” Ru-

MACHO (2). The choice of phosphine inﬂuences the nature

of the obtained complexes: while the small PMe₃simply

coordinates at the vacant site in the Ru^IIcomplex 2 (resulting in

complex 5), the bulkier PPh₃results in an isomeric,

pentacoordinated Ru⁰complex (6). Both isolated complexes

showed a similar reactivity toward alcohols and esters at low

catalyst loadings in the absence of a base. These observations

could be rationalized by quantum-chemical calculations, which

identiﬁed three factors determining the formation of the Ru^II

versus Ru⁰isomer: the steric bulk and electronic nature of the

phosphine employed and a stabilizing N−H···π-phenyl

interaction. Furthermore, it was shown that 5 and 6 are

precatalysts to the same catalytic cycle after phosphine

dissociation because no energetically feasible pathway was

located that did not include phosphine dissociation. The system

does not involve an on-cycle Ru⁰species. The Ru⁰complex 6

only serves as a rather unexpected resting state, which is

convertedbase-freeto the “activated” complex 2, which is

traditionally generated in situ from Ru-MACHO (1a) and a

base. The thorough computational evaluation leads to the

conclusion that the Dub-type mechanism poses the energetically

most favored pathway for alcohol dehydrogenation to the

corresponding aldehyde. A series of transition states that are

characterized by stabilizing hydrogen bonds between the NH

functionality and the substrate are the key aspect of this scenario

(i.e., MLA mechanism). This contrasts the commonly proposed

(Noyori-type) metal−ligand cooperative mechanism, which

requires a reversible N−H bound cleavage and was found to

be signiﬁcantly less feasible (ΔΔG^⧧= 17.1 kJ mol⁻¹). The

subsequent coupling of an aldehyde and an alcohol to the ester

was identiﬁed to occur on the metal complex without interim

generation of a free hemiacetal.⁴²A series of experiments

provided evidence that the addition of a phosphine ligand could

increase the lifetime of the deﬁned Ru-PNP catalytic system

after the reaction is complete. Finally, the catalyst’s performance

can be ﬁne-tuned by small amounts of base, which capture

detrimental impurities and do not harm the catalyst much.

Authors

Daniel J. Tindall − Catalysis Research Laboratory (CaRLa), D-

69120 Heidelberg, Germany

Maximilian Menche − Catalysis Research Laboratory (CaRLa),

D-69120 Heidelberg, Germany; BASF SE, Quantum Chemistry

& Molecular Simulation, D-67056 Ludwigshafen, Germany

Mathias Schelwies − BASF SE, Organic Synthesis, D-67056

Ludwigshafen, Germany

Rocco A. Paciello − BASF SE, Organic Synthesis, D-67056

Ludwigshafen, Germany

̈

Ansgar Schafer − BASF SE, Quantum Chemistry & Molecular

Simulation, D-67056 Ludwigshafen, Germany

Peter Comba − Institute of Inorganic Chemistry &

Interdisciplinary Center for Scientiﬁc Computing, Heidelberg

University, D-69120 Heidelberg, Germany; orcid.org/0000-

0001-7796-3532

Frank Rominger − Institute of Organic Chemistry, Heidelberg

University, D-69120 Heidelberg, Germany

A. Stephen K. Hashmi − Catalysis Research Laboratory

(CaRLa), D-69120 Heidelberg, Germany; Institute of Organic

Chemistry, Heidelberg University, D-69120 Heidelberg,

Germany; orcid.org/0000-0002-6720-8602

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.inorgchem.0c00337

Author Contributions

^†These authors contributed equally. The manuscript was written

through contributions of all authors. All authors have given

approval to the ﬁnal version of the manuscript.

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

The authors thank the analytical departments of the Organisch-

Chemisches Institut for excellent support. CaRLa is coﬁnanced

̈

by the Ruprecht-Karls-Universitat Heidelberg (Heidelberg

University) and BASF SE.

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* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c00337.

Experimental details, computational details, NMR spec-

tra, and Cartesian coordinates for the optimized

structures (PDF)

Accession Codes

CCDC 1958129−1958137 contain the supplementary crystallo-

graphic data for this paper. These data can be obtained free of

charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-

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Q

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Article Doi

Ru0 or RuII: A Study on Stabilizing the "activated" Form of Ru-PNP Complexes with Additional Phosphine Ligands in Alcohol Dehydrogenation and Ester Hydrogenation

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