Amide: Versus amine ligand paradigm in the direct amination of alcohols with Ru-PNP complexes

Article abstract of DOI:10.1039/c8cy00869h

The catalytic activity of a series of Ru-PNP pincer ligand complexes was studied in the direct amination of alcohols with ammonia. It turned out that all complexes of PNP ligands bearing a secondary amine showed no activity in this hydrogen-shuttling reaction sequence, while all complexes of homologous ligands bearing a tertiary amine gave active catalysts. Further comparative studies on catalysts bearing an acridine-based PNP pincer ligand and a PNP ligand of the Xantphos family provided valuable mechanistic insight that led to the design of a highly active catalyst. It appears that in the group of ligands studied here only ligands that do not form stable Ru-amido complexes are active alcohol amination catalysts.

Full text of DOI:10.1039/c8cy00869h

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Amide versus amine ligand paradigm in the direct
amination of alcohols with Ru-PNP complexes†
Cite this: DOI: 10.1039/c8cy00869h
Dennis Pingen, b Jong-Hoo Choi,c Henry Allen,d George Murray,d Prasad Ganji,e
a
Piet W. N. M. van Leeuwen, f Martin H. G. Prechtl
c and Dieter Vogt
*
*
The catalytic activity of a series of Ru-PNP pincer ligand complexes was studied in the direct amination of
alcohols with ammonia. It turned out that all complexes of PNP ligands bearing a secondary amine showed
no activity in this hydrogen-shuttling reaction sequence, while all complexes of homologous ligands bear-
ing a tertiary amine gave active catalysts. Further comparative studies on catalysts bearing an acridine-
based PNP pincer ligand and a PNP ligand of the Xantphos family provided valuable mechanistic insight
that led to the design of a highly active catalyst. It appears that in the group of ligands studied here only li-
gands that do not form stable Ru-amido complexes are active alcohol amination catalysts.
Received 29th April 2018,
Accepted 10th July 2018
DOI: 10.1039/c8cy00869h
rsc.li/catalysis
mined by the amount of catalyst, implies an intrinsic rate lim-
itation. After the initial alcohol dehydrogenation step, a new
Introduction
In view of its synthetic potential, the homogeneously
catalysed direct amination of alcohols with ammonia has
gained much attention since the first example was described
by Milstein in 2008.1 Since then, several other systems have
been developed that are able to convert both primary and sec-
ondary alcohols to amines.2–6 A number of studies have re-
vealed important information on the mechanism of the
reaction,7–9 but still there are discrepancies and parts that
need further elucidation. One particularly intriguing issue
concerns the large differences in activity of the systems
known. The usual assumption is that catalysis proceeds via
the “Borrowing Hydrogen”10 or “Hydrogen Shuttling”3
method; hydrogen is temporarily stored on the catalyst after
alcohol dehydrogenation to be re-used later in the hydrogena-
tion of the imine or enamine intermediate (Scheme 1). With
reference to this dual function of the catalyst, it was already
shown that the low concentration of intermediates, deter-
cycle can only start after the catalyst has delivered the hydro-
gen to the intermediate imine or enamine, present only in
amounts equivalent to the catalyst concentration at maxi-
mum, although dihydrogen formation would lead to higher
imine concentrations and also regenerate the catalyst.8 As the
amination of alcohols involves a dehydrogenation/hydrogena-
tion process that in part resembles a reductive amination re-
action, PNP pincer-type ligands affording active catalysts for
the latter reaction seem to be an ideal starting point.11,12
In their seminal work Milstein et al. employed the
acridine-based PNP pincer ligand 1 (Scheme 2).1 The same li-
gand was used later with Ru3IJCO)12 in the amination of both
primary and secondary bio-alcohols.2
Milstein and co-workers demonstrated
a long-range
metal–ligand cooperation, in which a hydrogen atom is
a Lehrstuhl Technische Chemie, Fakultät Bio- und Chemieingenieurwesen,
Technische Universität Dortmund, Emil-Figge-Straße 66, D-44227 Dortmund, Ger-
many. E-mail: dieter.vogt@tu-dortmund.de
b Chemical Materials Science, Department of Chemistry, University of Konstanz,
Universitätsstrasse 10, Konstanz, Germany
c Department of Chemistry, University of Cologne, Greinstrasse 6, 50939 Cologne,
Germany. E-mail: martin.prechtl@uni-koeln.de; Web: www.h2.bio
d EaStCHEM, School of Chemistry, University of Edinburgh, King's Buildings,
Joseph Black Building, West Mains Road, Edinburgh EH9 3JJ, Scotland, UK
e Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of
Science and Technology, Av. Països Catalans 16, 43007 Tarragona, Spain
f Laboratoire de Physique et Chimie de Nano-Objets, INSA, 135 Avenue de
Rangueil, F-31077 Toulouse, France
Scheme
1 Concept of “Hydrogen Shuttling”. A) Alcohol
dehydrogenation in which the hydrogen is stored on the catalyst, B)
condensation of the carbonyl compound with the amine followed by
C) hydrogenation of the imine, using the metal hydride generated in
the first step.
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8cy00869h
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150 °C (Chart 1A, ●). When
4
mol% of KOtBu was
added at the start of the reaction, mimicking the reactions
shown in Scheme 3, catalysis was almost completely in-
hibited (Chart 1A, ■). The reaction with base was repeated
but in this instance after 8 h, 10 mol% of benzaldehyde were
added. Immediately after the addition, catalysis started and
conversion went to completion within about 24 h (Chart 1B).
In our earlier mechanistic studies on the amination of cyclo-
hexanol with the RuHClIJCO)IJPPh3)3/Xantphos system it was
found that the dihydride RuH2IJCO)IJPPh3)IJXantphos) was
formed by treatment with KOtBu and alcohol.8 This
dihydride, prepared in situ or as an isolated complex, is inac-
tive as catalyst precursor in the alcohol amination reaction.
However, the catalytic cycle can be started by addition of the
intermediate carbonyl compound (cyclohexanone in this
case). This indicates the dilemma intrinsically hampering all
‘borrowing hydrogen’ reactions. Due to the sequence of con-
secutive reactions, with coupled equilibria of dehydrogena-
tion (of the alcohol) and hydrogenation (of the imine) none
of the intermediates (ketones and imines) can be present in
a concentration higher than that of the catalyst. As a result,
those reactions are typically slow and therefore require
higher amounts of catalyst; typically 1–5 mol%. This is why
increasing the steady state concentration of the intermediate
Scheme
2 Milstein's acridine PNP ligand 1 and Ru complex 2
employed in the direct amination of primary alcohols.1
transferred to the C9 position of the acridine ligand back-
bone, leading to dearomatisation and amide bonding to the
Ru centre. It was suggested this might play a role in cataly-
sis.13 Mechanistic studies accompanied by DFT calculations,
recently performed by the group of Hofmann, suggest that
this is not a necessity for catalyst activity.7
However, another prominent example of an active catalyst
not providing any metal–ligand cooperativity is the analogous
complex with Xantphos, reported by Beller and co-workers.5
Investigation of further ligands revealed various Ru precur-
sors in combination with Xantphos-type ligands that show
good activity in the amination. Nevertheless, Milstein's com-
plex (2) remains one of the most active catalysts so far that
achieves a very high selectivity.6,8
Hofmann and co-workers investigated the analogous PCy2
derivative of ligand 1, which forms a similar Ru complex 3.7
Treatment of complex 3 with NaOtBu and 2 eq. of alcohol
resulted in dearomatisation of the backbone, with a saturated
C9 position and amide bonding to the Ru centre (Scheme 3,
4). Complex 4 readily forms the NH3 adduct 5 that was also
found to be the main remaining species after completion of
the alcohol amination catalysis.
It was concluded that the ‘long range metal–ligand coop-
eration’ is not a necessity for catalysis.7 In this contribution
we study the influence of base and ketone on a few known
PNP catalyst precursors containing hydride, chloride and/or
amide anions in order to establish general requirements.
Subsequently several new ligands will be introduced
containing secondary and tertiary amines as the central li-
gand atom. A simple PNP ligand with a tertiary amine and an
aliphatic chain, i.e. no dearomatisation can take place,
turned out to be one of the fastest catalysts known to date.
Results and discussion
First we studied the behaviour of Milstein's complex 2 in
amination with respect to the presence of base and ketone/
aldehyde. The amination of benzyl alcohol goes to comple-
tion with high selectivity to benzylamine within 8 hours at
Chart 1 (A) Amination of benzylalcohol using complex 2, with (■) and
without KOtBu (●) and (B) KOtBu (4 mol%) added initially, followed by
addition of 10 mol% benzaldehyde (arrow) after 8 h (▲). Conditions: 1
mol% complex 2, 5 mmol benzylalcohol, 15 mL toluene, 2.5 mL NH3,
Scheme 3 Formation of the dearomatised complex 4 and its NH3
adduct 5, reported by Hofmann et al.7
150 °C,
8 h. Black = benzylalcohol, red = benzylamine, blue =
benzaldehyde, green = dibenzylimine.
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speeds up those reactions. In the present case benzaldehyde
activates the catalyst in the same fashion, i.e. imine forms
and hydrogens are transferred to the imine providing an ac-
tive catalyst for the dehydrogenation again.
Further studies underline the subtle differences in the
amination of primary and secondary alcohols with the differ-
ent systems. While the Xantphos system RuHClIJCO)IJPPh3)-
IJXantphos) showed a three-fold increase in activity in the
amination of cyclohexanol upon addition of 10 mol% cyclo-
hexanone,8 the rate of amination of benzyl alcohol with 2
was only moderately increased on addition of 10 mol% of
benzaldehyde (Graph S21, ESI†).
Based on the reports by Milstein13 and Hofmann7 one
would expect that in the presence of KOtBu the dearomatised
species analogous to 4 or 5 are formed. The conclusion we
can draw from the lack of activity under these conditions is
that, if formed, those species are not active in the direct
amination of alcohols under the conditions employed here.
In analogy with Xantphos (vide supra) one would expect
that the dihydride formed from 1 is also an inactive catalyst
(Scheme 4, 6). Treatment of RuHClIJCO)IJPPh3)IJXantphos) with
KOtBu results in a dihydride as was shown by Williams14 and
by us.8 In case of complex 6, this dihydride has the possibil-
ity to undergo the dearomatisation reaction at elevated tem-
perature to form complex 7 or its NH3 adduct.
Chart 2 shows that the system generated in situ from
RuH2IJCO)IJPPh3)3 and ligand 1 is an active catalyst for the di-
rect amination of benzyl alcohol. This indirectly indicates
that complex 7, which is analogous to 4, is not formed, as it
was shown that complex 4 was not active. Unfortunately, at-
tempts to unambiguously decide whether 7 is formed in the
reaction of RuH2IJCO)IJPPh3)3 in combination with ligand 1
failed. Reaction of complex 2 with NaH in the presence of 2
equiv. of benzyl alcohol did give the orange complex 7 as was
shown by Milstein and co-workers.13,15 Thus, the final ques-
tion for this type of acridine-based Ru-PNP pincer complexes,
which of the species present actually is the active one re-
mains open and will require further studies.
Chart
2
Amination of benzylalcohol using the in situ system
RuH2IJCO)IJPPh3)3/1. Conditions:
RuH2IJCO)IJPPh3)3/1, 15 mL toluene, 2.5 mL NH3, 150 °C.
benzylalcohol, = benzylamine, = benzaldehyde, = dibenzylimine.
5 mmol benzylalcohol, 1 mmol%
■
=
est analogue. Upon coordination of 10 to HRuClIJCO)IJPPh3)3
under ligand exchange an amide bond can be formed. This
reaction was found to proceed under HCl elimination to give
11 (Scheme 5).
1
The hydride region of the H NMR spectrum shows a dou-
ble triplet with a typical trans H–P coupling of 103 Hz and a
smaller cis H–P coupling of 24 Hz (Fig. S5, ESI†), confirming
formation of complex 11. The 31P NMR spectrum indicates
free PPh3, a doublet, and a triplet, each with a coupling con-
stant of 23 Hz, typical of cis P–P coupling constants (Fig. S6,
ESI†).6 From this, it can be concluded that indeed complex
11 was formed.
Complex 11 neither showed activity under the standard
amination reaction conditions, nor in the presence of base or
ketone (Graph S20, ESI†).
Based on these additional observations and taking into ac-
count the current state of knowledge we continued our stud-
ies with Ru complexes of aliphatic PNP ligands (12–15), devel-
oped in the group of Prechtl.16–18 All these complexes are
hydride, dihydride, or multi-hydride complexes, including
non-classical hydrides. In the non-classical hydrides, H2 is co-
ordinated via the σ-bond (Fig. 1).19 In these complexes H2
and classical hydrides have been shown to be in fast
exchange.20
Though all fairly similar, there are a few important differ-
ences between these complexes. The main one is that in com-
plexes 13 and 15 the ligand binds as an amide with the
metal; the amine is deprotonated upon complexation,
forming a Ru hydride. The carbonyl-metal bond in 14 and 15
A more rigid ligand of the Xantphos family was designed
that bears analogous to 1 nitrogen in 10-position of the back-
bone instead of the usual oxygen atom (AcridanPhos 10,
Scheme 5). As the 9-position is occupied by two methyl
groups, this ligand represents an analogue of the
dearomatised state of the acridine-based diphosphine 1. It
lacks the methylene groups of Milstein's ligand, but unfortu-
nately so far we did not succeed in the synthesis of the clos-
Scheme 4 Milstein's acridine-based PNP pincer ligand (1) and the
possible complexes 6 and 7 formed by reaction with RuH2IJCO)IJPPh3)3.
Scheme 5 Reaction of AcridanPhos (10) with RuHClIJCO)IJPPh3)3.
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Fig. 1 Multi-hydride Ru complexes with aliphatic PNP ligands.
is most likely strong, whereas H2 should be weakly bound in
12 and 13, which can be easily replaced or will even dissoci-
ate thermally.21,22 Complexes 12 and 14 bear a tertiary amine
in the ligand backbone, coordinated via the nitrogen lone
pair. Therefore, these complexes contain a second ionic li-
gand, in both cases a second hydride.
Complexes 12–15 were examined as catalysts for the
direct amination of cyclohexanol and benzyl alcohol. First,
complexes 13 and 15 were employed in the direct amination
of cyclohexanol. Generally,
a large excess of NH3 was
employed, which is beneficial for the selectivity and conver-
sion. As the initial complexes are hydridic, addition of
ketone may provide a route for activation. Both complexes
13 and 15 appeared to be inactive (Graph S1 and S2, ESI†).
These reactions were initially performed without additive,
showing no activity for the first 22.5 hours. After this time,
10 mol% of cyclohexanone were added, but that did not
lead to activity either. In our previous mechanistic studies it
appeared that for certain complexes a base is required to
yield an active complex. Usually, the base is added to ab-
stract HCl from the complex. These complexes do not con-
tain chloride, but the base might also be beneficial for de-
protonation of the alcohol. The reactions were therefore
conducted again under the same conditions but now KOtBu
was added. Graph S3 and S4† in the supporting information
show that this was not beneficial either. As complexes 13
and 15 are not active for secondary alcohols, benzylalcohol
was used as a primary alcohol. Now the conversion reached
20% but the main product was dibenzylimine (Graph S5
and S6, ESI†). Furthermore changing the solvent from
t-amylalcohol to toluene (Graph S7 and S8, ESI†)23 did not
result in any conversion. Having established that amides 13
and 15 are poor catalysts, we employed amine complexes 12
and 14 under the same conditions as in the amination of
cyclohexanol.
Both complexes show activity, although the reaction
does not go to completion within 52 h reaction time
(Chart 3). Next the reactions with complexes 12 and 14
were repeated in the presence of 10 mol% of cyclohexa-
none (Graph S9 and S10, ESI†). Surprisingly, in the case of
complex 12 and 14, the activity strongly decreased and ap-
parently, cyclohexanone inhibits catalysis in this case.
When fresh cyclohexanone and ammonia were added after
23.5 hours to catalyst 12 the reaction was completely
suppressed (Graph S11, ESI†). These type of multi-hydride
Ru-PNP complexes are known to decarbonylate acetone,
forming two equivalents of methane and a Ru carbonyl
complex24 Perhaps cleavage of cyclohexanone takes place
Chart 3 Amination of cyclohexanol employing complex 12 (A) and 14
(B). Conditions: 0.04 mmol catalyst, 5 mmol cyclohexanol, 15 mL
t-amylalcohol, 2.5 mL NH3, 150 °C.
cyclohexylamine, cyclohexanone,
dicyclohexylimine, = dicyclohexylamine.
■
=
cyclohexanol,
=
=
=
= cyclohexylimine,
with formation of CO and a Ru metallacycle, the inactive
complex 16 (Scheme 6).
The potential formation of the Ru metallacyclic compound
16 as a product or intermediate was investigated by MS. From
the reaction mixture species 16 was detected by LIFDI-MS;
the mass found agrees with the proposed structure (Fig. S1
and S2, ESI†). The relative stability of 16 might account for
the observed deactivation. On the other hand, addition of an
aldehyde, if decarbonylated, would lead to a much less stable
Ru n-alkyl or aryl species, most likely not shutting down ca-
talysis. The amination of cyclohexanol with complexes 12 and
14 was performed again with benzaldehyde as additive
(Graph S12 and S13, ESI†). Now indeed, the reaction
proceeded more smoothly and no deactivation was observed.
For complex 14 the reaction now went to completion (Graph
S12 and S13†).
Scheme 6 Reaction of Ru PNP complex 12 with cyclohexanone via
decarbonylation.
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Performing the reaction with benzylalcohol as substrate
resulted in inactive systems for both complexes. However,
after the addition of 10 mol% benzaldehyde, complex 12 does
show some activity but is quickly deactivated as well. Only
dibenzyl imine was formed in this case. Complex 14 on the
other hand, remained completely inactive (Graph S16 and
S17, ESI†). In conclusion, complexes 12 and 14 were shown
to be active in the direct amination of cyclohexanol. Remark-
ably, complexes 13 and 15 with PNP ligands having a second-
ary amine in the backbone that form a Ru–amide bond are
not active while the ones with a tertiary amine in the back-
bone are active.
Encouraged by the results of the alkyl amine ligands the
commercially available Ru complex 17 (Fig. 2), an ester hy-
drogenation25 and methanol dehydrogenation catalyst,26,27
was tested in the amination of cyclohexanol. Complex 17 is
closely related to the previously tested complexes 13 and 15,
containing the coordination sphere of catalysts 2 and 3.
Because of the secondary amine in the backbone, 17 is
likely to form an amide-metal bond under alcohol amination
conditions.28 In line with our earlier observations we
expected this species to be inactive. The results with complex
17 are shown in Chart 4.
Chart 5 Amination of cyclohexanol employing complex 18 in the
presence of KOtBu. Conditions: 0.04 mmol 18, 5 mmol cyclohexanol,
0.5 mmol KOtBu, 15 mL t-amylalcohol, 2.5 mL NH3, 150 °C. ■ =
cyclohexanol,
=
cyclohexylamine,
=
cyclohexanone,
=
cyclohexylimine,
= dicyclohexylimine, = dicyclohexylamine.
converted to a tertiary amine (Fig. 2). Initially the same reac-
tion parameters were employed as with all other precursors
previously tested, which resulted in no activity for complex
18 (Graph S23, ESI†). However, addition of base (KOtBu)
resulted in a very active system for the amination of both sec-
ondary and primary alcohols (Chart 5, also see Graph S24,
ESI†). This new complex turns out to be one of the most ac-
tive catalyst for the direct amination of secondary alcohols so
far (TOF = 74, compare Table 1). For comparison, the TOF's
of various systems determined at 20% conversion of the re-
spective alcohol are given in Table 1.
In fact, complex 17 was not active at all and could neither
be activated by the addition of carbonyl compounds nor by
base or by changing the solvent. Subsequently complex 18
was synthesized in which the amine in the backbone is
It is apparent that the closely related complexes 14 and 18
behave quite differently in catalysis. Activation of the
trans-dihydrido complex 14 is relatively difficult and even af-
ter addition of a carbonyl compound as hydrogen acceptor
stays behind complex 18 in activity (see also ESI†). A similar
behaviour was observed for H2RuIJCO)IJPPh3)Xantphos, which
Fig.
2 Ru bisIJdiphenylphosphino-ethyl)amine carbonyl hydride
complex (17) and analogous N-methylated complex 18 bearing PIJtBu)2
groups.
Table 1 Overview of current selective direct amination systems with re-
spective turnover frequencies (TOF)
Complex
TOFa (h−1
)
Conversion/selectivity
Complex 18
74
37.5
95/99
82/85
RuHClIJCO)IJMilstein acridine)b
RuHClIJCO)IJTriphos)b,d
RuHClIJXantphos)
28.6 (ref. 9) 89/90
12.7 (ref. 8) 95/100
12.4 (ref. 3) 99/100
9.6 (ref. 6)
8 (ref. 3)
Ru3IJCO)12/Milstein acridinec
RuHCl(CO)(PPh3)(Sixantphos)
Ru3IJCO)12/CatacXium Pcyc
RuHCl(CO)(PPh3)(Xantphos)
RuHClIJCO)IJPPh3)IJThixantphos)
70/100
95/91
95/100
95/43
5.6 (ref. 6)
2.1 (ref. 6)
RuHClIJCO)IJTriphos) [NaBArF]b,e 200 (ref. 9) 100/25
a
Chart
4 Amination of cyclohexanol employing complex 17.
Turnover frequencies calculated at 20% conversion. Reactions
Conditions: 0.05 mmol complex 17, 5 mmol cyclohexanol, 15 mL
t-amylalcohol, 2.5 mL NH3, 150 °C, 25.5 h. ■ = no additives or
changes, ● = 10 mol% benzaldehyde added, ▲ = 1 mol% KOtBu added,
conducted with 1 mol% complex at 150 °C with cyclohexanol as a
b
substrate. Benzylalcohol as a substrate was used as it was inactive
in the amination of cyclohexanol, secondary alcohols in general.1
▼
= ◆ = toluene as solvent, black =
10 mol% KOtBu added,
c
d
Prepared in situ, 2 mol% catalyst, 170 °C. 0.28 mol% catalyst, T =
155 °C. e 0.2 mol% catalyst.
cyclohexanol, red = cyclohexylamine, blue = cyclohexanone.
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also required a hydride acceptor for activation, but still
remained behind in activity with respect to the complex
HRuClIJCO)IJPPh3)Xantphos.8 For a deeper understanding of
these subtle but important differences more detailed studies
will have to be performed in the future.
mass spectrometer equipped with a LIFDI 700 ion source
(Linden CMS).
Synthesis
The syntheses of compounds 12 and 13 are described in a lit-
erature procedure.17 The synthesis of compounds 14 and 15
are described in a literature procedure.16 Compounds 8 and
9 are described in a previous paper,6 following a literature
procedure for the synthesis of 9.29
Synthesis of 4,5-bisIJdiphenylphosphino)-3,6,9,9-tetramethyl-
9,10-dihydroacridine ligand (10). Acridine based phosphine
(10) was synthesised from a literature known compound
such as 4,5-dibromo-3,6,9,9-tetramethyl-9,10-dihydroacridine
via lithiation and phosphination method. 3,6,9,9-Tetramethyl-
9,10-dihydroacridine was prepared according to the reported
methods.30
Conclusions
Previously it was shown that aromatization/dearomatisation
of the acridine backbone of Milstein's ligand might not be a
prerequisite for the formation of active catalysts. We have
now demonstrated that in acridine ligand 10, in which the
dearomatisation is blocked, does not form an active catalyst.
In several easily accessible alkyl PNP ligands and their com-
plexes we have shown that Ru PNP pincer complexes
containing a secondary amine in the backbone that are able
to form Ru-amide species under reaction conditions are in-
variably inactive in the direct alcohol amination with ammo-
nia. On the contrary, the corresponding PNP ligands with a
tertiary amine in the backbone form active catalysts. This
leads us to postulate that in order to obtain an active cata-
lyst, no amide bond should be present. Based on these in-
sights a new catalyst system based on the aliphatic PNP
ligand bis(di-tert-butyl phosphinoethyl)methylamine was pre-
pared with the preferred precursor RuHClIJCO)IJPPh3)3, which
on activation with base represents one of the most active
catalysts for the direct amination of alcohols with ammonia
reported so far.
In an oven dried Schlenk-tube was added 4,5-dibromo-
3,6,9,9-tetramethyl-9,10-dihydroacridine (1.0 g, 2.53 mmol)
and anhydrous THF (20 mL) was charged under argon atmo-
sphere. The reaction mixture was degassed with vacuum/
argon cycles and then cooled to −78 °C. To this solution was
added dropwise n-BuLi (2.5 M in hexane, 7.59 mmol, 3.0
equiv.) via a syringe. The resulting reaction mixture was
stirred at −78 °C for 10 min followed by the dropwise addi-
tion of chlorodiphenylphosphine (1.67 g, 7.59 mmol, 3.0
equiv.) via a syringe over 10 min. The reaction mixture was
stirred at −78 °C for 1 h, slowly warmed to room temperature
and stirred at this temperature for overnight (16 h). The reac-
tion mixture was quenched with degassed water (3.0 mL) and
the solvent was removed under vacuum. To this mixture
anhydrous dichloromethane (20 mL) was added and the or-
ganic layer was washed with water (10 mL), dried over
Na2SO4 and evaporated to dryness to give the residue. Metha-
nol (10 mL) was added to the residue and stirred at RT for
0.5 h, the resulting white precipitate was collected by filtra-
tion and washed with methanol (5 mL) to give the desired
phosphine as a white solid, yield (858 mg, 56%). 1H NMR
(500 MHz, 298 K, CDCl3, δ = ppm): 8.74 (t, JHH = 8.8 Hz, 1H,
Experimental
General considerations
All chemicals were purchased from Sigma-Aldrich and were
used as received unless otherwise noted. Complex 17 and all
other Ru-precursors were purchased from Strem and used as
received. Solvents (t-amylalcohol, toluene) were used after dry-
ing and degassing followed by purging with Ar. Cyclohexanol
was degassed and purged with Ar prior to use. KOtBu was
purchased from Alfa Aesar and was used as received. Com-
pound 10 was prepared in the group of Piet W. N. M. van
Leeuwen. The autoclaves are in-house made stainless steel re-
actors equipped with a manometer, 50 μL sample unit and a
PT100 temperature sensor. Samples are measured on a
GC2010 Ultra 2 column (25 m, 0.2 mm id). Samples were
subjected directly to GC without further workup. Liquid NH3
was dosed using a Bronkhorst Liquiflow Mass Flow Control-
4
NH), 7.36–7.23 (m, 20H, 2xPPh2), 7.20 (d, JHH = 1.6 Hz, 2H,
4
CH backbone), 6.60 (d, JHH = 2.1 Hz, 2H, CH backbone),
2.19 (s, 6H, 2xCH3), 1.59 (s, 6H, 2xCH3). 13C NMR (126 MHz,
298 K, CDCl3, δ = ppm): 136.1, 133.9, 133.8, 133.8, 132.5,
129.3, 129.1, 128.6, 128.5, 128.4, 128.4, 127.3, 36.8, 30.3, 21.2.
31P{1H} NMR (202 MHz, 298 K, CDCl3, δ = ppm): −20.9 (s);
HRMS (ESI): C41H38NP2 [M + H]+ calcd.: 606.2480, found
606.2489.
1
ler. H NMR, 31P NMR and 13C spectra were recorded on 400
MHz and 500 MHz Varian Mercury and 300 Bruker Avance II,
400 MHz and 500 MHz Bruker Avance spectrometers (s =
singlet, d = doublet, t = triplet, dd = double doublet, dt = dou-
ble triplet, br. s. = broad singlet). Infrared spectra (IR) were
measured on a Bruker Alpha spectrometer equipped with a
Diamond-ATR-IR unit. Data are reported as follows: absorp-
tion  [cm−1], weak (w), medium (m), strong (s). LIFDI-MS
(liquid injection field desorption/ionization-mass spectrome-
try) was performed using a Waters micromass Q-ToF-2™
Reaction of 10 with RuHClIJCO)IJPPh3)3. AcridanPhos 10
(30.3 mg, 0.05 mmol) was weighed into a Wilmad-Young
NMR tube. To this, RuHClIJCO)IJPPh3)3 (47.6 mg, 0.05 mmol)
was added. The solids were degassed and purged with argon.
Degassed and dry toluene-d8 was added and the mixture was
heated to 130 °C for 3 h. NMR analysis confirmed complexa-
tion. 1H NMR hydride region (400 MHz, 298 K, toluene-d8,
2
δ = ppm): −6.71 (dt, JHP = 103.6, 24). 31P{1H} NMR (162 MHz,
2
298 K, toluene-d8, δ = ppm): 34.1 (d, JPP = 24 Hz), 31.4
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2
(t, JPP = 24 Hz). IRIJcm−1): 3052 (m), 1962 (CO, s), 1584 (w),
For access to LIFDI-MS analysis, we gratefully acknowledge
Prof. Dr. T. Braun, Dr. M. Ahrens and J. Berger (Humboldt-
University of Berlin, Germany).
1457 (m), 1403 (s), 1317 (m), 1260 (s), 1087 (s), 1026 (m), 998
(m), 741 (s), 691 (s). HRMS (ESI): C60H52NOP3Ru [M − H−]+
calcd: 996.2223, found: 996.2236.
Reaction of cyclohexanone with complex 12 resulting in
complex 16. In a Teflon capped Wilmad-Young NMR tube
(Wilmad 300 MHz), complex 12 (20 mg, 0.04 mmol) and
cyclohexanone (5.2 μL, 0.05 mmol) were placed. To this, deu-
terated toluene (0.5 mL) was added and the NMR tube was
close under inert atmosphere. The mixture was heated at 80
°C and NMR was recorded at t = 0, 1, 2, 4, 7, 10, 20, 24, 30, 40,
50, 60, 70 h. After 70, the solvent was remove in vacuo and the
black liquid residue was subjected to IR and LIFDI-MS.
Compound 18 was synthesized as followed31. In an argon
purged Schlenk tube PNP-Me ligand (160 mg, 0.43 mmol)
was dissolved in toluene (6 mL). After addition of
RuHClIJCO)IJPPh3)3 (280 mg, 0.3 mmol) the mixture was
refluxed for 5 h. After this, the solvent was removed via can-
nula and the white solid was washed with pentane (2 × 5 mL)
Notes and references
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1
and was stored at −34 °C. Yield: 70%. H NMR (300 MHz, 298
K, CDCl3, δ = ppm): 2.64 (m, 4H, NCH2), 2.53 (s, 3H, NCH3),
3
2.22 (m, 4H, PCH2), 1.56 (t, 18H, JPH = 6.6 Hz, PC(CH3)3),
3
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=
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ppm): 207.2 (CO), 65.8 (t, JCP = 8.8 Hz, NCH2), 47.6
(s, NCH3), 38.6 (t, JCP = 5.6 Hz, PIJC(CH3)3)), 36.6 (t, JCP
10.3 Hz, PIJC(CH3)3)), 32.1 (PIJC(CH3)3)), 31.3 (t, JCP = 2.8 Hz,
C
apt
NMR (75 MHz, 298 K, CDCl3, δ =
2
1
1
=
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General procedure for the catalysis
Complex was weighed in the glovebox into a Schlenk tube.
The Schlenk tube was removed from the glovebox (kept un-
der Ar) and degassed solvent (15 mL) was added via syringe.
The complex was dissolved followed by addition of cyclo-
hexanol (520 μL, 5 mmol) via syringe. The mixture was trans-
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was closed and liquid NH3 (2.5 mL, 97.5 mmol) was dosed to
the autoclave. The whole was then heated to 150 °C. Samples
were taken at t (h) = 0, 0.5, 1, 2, 3.75, 5.5, 7.5, 10, 23.5, 25,
28, 32, 48, 52.
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Acknowledgements
PWNMvL and PG acknowledge the European Union for ERC
Advanced Grant (NANOSONWINGS 2009-246763) and the
ICIQ support groups, JHC and MHGP acknowledges the DFG
(Heisenberg program), the Ministerium für Innovation, Wis-
senschaft und Forschung NRW (MIWF-NRW) Research Pro-
gram for the Scientist Returnee Award for financial support.
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