Dehydrogenative Coupling of Ethanol and Ester Hydrogenation Catalyzed by Pincer-Type YNP Complexes

Article abstract of DOI:10.1021/acscatal.6b02324

The "Y" donor group (Y = -OMe, -SEt, -PPh₂, -NH₂, -NMe₂, -Py, pyrrolidinyl, quinolyl) of the pincer-type ruthenium complexes RuHCl(CO)[κ³-YNP] has a dramatic influence on the catalytic activity in the dehydrogenative homocoupling and cross-coupling of ethanol and ester hydrogenation reactions. The observations are connected with the mechanisms of the catalytic reactions, and this paper provides evidence for ester C-O bond formation/cleavage assisted by the bifunctional catalysts in an outer-sphere fashion, reminiscent of the Tishchenko chemistry.

Full text of DOI:10.1021/acscatal.6b02324

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Article
Dehydrogenative coupling of ethanol and ester
hydrogenation catalyzed by pincer-type YNP complexes
Dmitry Gusev
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b02324 • Publication Date (Web): 06 Sep 2016
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Dehydrogenative coupling of ethanol and ester hydrogenation cata-
lyzed by pincer-type YNP complexes.
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Dmitry G. Gusev*
Wilfrid Laurier University, Department of Chemistry and Biochemistry, 75 University Ave. W., Waterloo ON N2L
3C5, Canada.
KEYWORDS: alcohol dehydrogenation, ester hydrogenation, ester synthesis, amide synthesis, catalytic mechanisms
ABSTRACT: The “Y” donor group (Y = -OMe, -SEt, -PPh2, -NH2, -NMe2, -Py, pyrrolidinyl, quinolyl) of the pincer-type ru-
thenium complexes RuHCl(CO)[κ3-YNP] has a dramatic influence on the catalytic activity in the dehydrogenative homo-
and cross-coupling of ethanol and ester hydrogenation reactions. The observations are connected with the mechanisms of
the catalytic reactions, and this paper provides evidence for the ester C-O bond formation/cleavage assisted by the bi-
functional catalysts in an outer-sphere fashion, reminiscent of the Tishchenko chemistry.
The seminal work of Milstein and co-workers1 in 2005 –
2007 demonstrated the impressive synthetic potential of
the catalytic homo- and cross-coupling of primary alco-
hols and the reverse processes, hydrogenation of esters
and amides of Scheme 1.1 This area of research has grown
in the last decade, and the progress has been documented
in many contemporary reviews and book chapters.2, 3 Ex-
tensive computational studies have been devoted to the
elucidation of the catalytic mechanisms. 3-6
Scheme 1.
Our complex, OsHCl(CO)[PiNH(CH2)2NHPtBu2] (1, Pi
= picolyl group, -CH2Py), is an efficient pre-catalyst for
the dehydrogenative coupling of alcohols and ester hy-
drogenation.7 Among the unique useful properties of 1 is
the compatibility with alkenes that allows working with a
broad range of unsaturated substrates, typically with 98-
100% retention of the alkene functionalities. Furthermore,
complex 1 is the only known efficient catalyst for the syn-
thesis of amides from the volatile primary alcohols and
amines with b.p. < 100 °C, such as N-alkyl acetamides.
Chart 1. Ruthenium complexes 2 - 12.
The results of this paper are presented and discussed
below, and this study confirms the overall superior cata-
lytic efficiency of the osmium vs. ruthenium metal center
of 1 and 2 in the reactions of Scheme 1, as well as the privi-
leged role of the PiNP-tBu ligand. This paper also reports
several striking observations of the dramatic influence of
the Y group of the catalysts of Chart 1 on the reactions of
Scheme 1 that provide some guidance for future catalyst
design. At the end, this paper revisits the catalytic mech-
anisms of the reactions of Scheme 1 (X = O) to provide
experimental evidence for the ester C-O bond for-
mation/cleavage assisted by the bifunctional catalysts in
an outer-sphere fashion, reminiscent of the Tishchenko
chemistry. The active form of the osmium catalyst,
OsH2(CO)[PiNH(CH2)2NHPtBu2], is indeed highly active
In continuation of the recent work, we were interested
in
making
the
ruthenium
analogue,
RuHCl(CO)[PiNH(CH2)2NHPtBu2] (2), and exploring the
related new pincer-type YNP complexes 3 - 10 of Chart 1.
Through a comparative study of 2 – 10 together with the
known compounds 11 (Ru-MACHO)8 and 12,9 we wanted
to probe the role and importance of the Y ligand group in
the catalytic reactions of Scheme 1, and learn whether the
catalyst efficiency could be usefully enhanced through the
systematic modifications of the ligand structure.
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(TOF > 7,000 h-1) for the Tishchenko synthesis of ethyl
acetate from acetaldehyde.
Table 1. Selected spectroscopic data for the complex-
1
2
es of Chart 1.a
3
4
Results
complex δ RuH, 2J(H-P)b δ 31P δ CO, 2J(C-P)b ν(CO)c
The YNP ligands of 1 - 10 are modular by design. Thus,
assembling a representative ligand library is straightfor-
ward via the alkylation and condensation reactions of
Scheme 2, detailed in the Experimental part. The alkyla-
tion is solventless and the excess ethylenediamine works
as the reaction media and the base; the product diamines
were isolated by distillation in typical 60 to 80% yields.
These diamines react with bulky ClPR2 selectively at the
primary nitrogen, and the products were isolated in excel-
lent yields by distillation or (for the less volatile YNP lig-
ands) by evaporation of the THF solutions. The amine
ligand H2N(CH2)2NH(CH2)2NHPtBu2 was obtained in one
step from diethylenetriamine and ClPtBu2, in a 85% yield.
5
6
7
8
2
-15.10, 26.4
-14.44, 28.4
-15.37, 28.4
-15.79, 27.6
-16.19, 30.4
-16.31, 25.2
-16.40, 26.4
-16.18, 28.4
-16.25, 28.0
-14.33, 25.9
125.8 207.70, 18.1
99.5 206.51, 19.3
1909.7
1920.9
1908.8
1908.0
1917.7
1917.4
1907.0
1903.5
1903.7
1917.4
3
4
124.6 206.85, 19.5
127.4 207.62, 20.1
139.6 206.87, 21.4
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117.3
206.54, 19.3
8
9
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12
125.6 207.14, 18.7
126.4 208.32, 18.8
125.6 208.40, 19.5
70.8
205.83, 16.2
Scheme 2.
aAll in dichloromethane. bTwo-bond spin coupling, Hz.
cStretching vibration, cm-1 (broad absorption).
Table 2. Selected gas-phase DFT (M06-L) data for
complexes 2 and 4 – 12.
complex
Ru-Y, Å
Ru-P, Å
2.305
2.297
2.297
2.251
Ru-N2, Å
2.234
2.266
2.236
2.234
2.267
2.241
BDEa
19.3
13.5
2
Ru-N1, 2.159
Ru-N1, 2.271
Ru-N1, 2.216
Ru-O, 2.304
Ru-S, 2.478
Ru-N1, 2.235
Ru-N1, 2.302
Ru-N1, 2.319
Ru-N1, 2.153
4
Scheme 3.
5
17.5
13.4
21.4
20.1
19.6
20.7
17.9
6
7
2.310
8
2.283
2.283
2.285
2.256
9
10
12
2.238
2.246
2.204
Two complexes of this work (3 and 8) were obtained by
ligand exchange with RuHCl(CO)(AsPh3)3. However, our
preferred approach to the ruthenium complexes of Chart 1
was based on heating a mixture of [RuCl2(COD)]n, a YNP
ligand, and lithium in anhydrous ethanol (see Experi-
mental for details), in a fashion similar to the reported
synthesis of OsHCl(CO)[PiNH(CH2)2NHPtBu2] from
[OsCl2(p-cymene)]2.7 This worked most successfully with
PiNP-tBu and afforded complex 2 as a crystalline air-
stable solid (3.3 g, 82.5% product yield, see Scheme 3 and
Figure S1). Satisfactory elemental analyses were obtained
for all complexes of this work. The key spectroscopic data
in Table 1 suggest that complexes 1 – 10 adopt the same
coordination geometry with the hydride trans to the chlo-
ride and the carbonyl cis to the phosphorus group; thus
the κ3-YNP ligands are coordinated in a mer- fashion, as
shown in Chart 1. The 31P NMR shifts of the κ3-YNP-tBu
ligands on ruthenium are all very similar, δ 124.6 – 126.4,
when Y is a nitrogen donor. The CO stretching frequen-
cies suggest that in the series of the κ3-YNP-tBu com-
pounds, ruthenium is most electron-rich in the dimethyl-
amine and pyrrolidine complexes 9 and 10, and the least
so in the ether and thioether complexes 6 and 7.
aRu-Y bond enthalpies, kcal/mol.
We assessed some structural parameters of the ruthe-
nium complexes and the relative hemilability of the Y-
groups with the help of DFT (M06-L) calculations; the
relevant data are collected in Table 2. The Ru-Y bond dis-
sociation enthalpies (BDE) were calculated as enthalpy
differences of the 6-coordinate, 18-electron complexes 2 –
12 and the corresponding 5-coordinate, 16-electron spe-
cies formed by rotation of the Y-group out of the coordi-
nation sphere of the metal as illustrated in Figure 1 for 2.
Most complexes in Table 2 have similar Ru-Y bond en-
thalpies, in the range of 19.3 to 21.4 kcal/mol. Complex 6
possesses a weak Ru-O bond (13.4 kcal/mol) as expected.
The Ru-N1 bond of the quinoline complex 5 is destabi-
lized (17.5 kcal/mol vs. 19.3 kcal/mol in 2), presumably
due to repulsion between the quinoline and the carbonyl
(note the increased angle N1-Ru-C1 = 99.7 in 5 vs. N1-Ru-
C1 = 96.8 in 2). The weakly bonded pyridine fragment of 4
(BDE = 13.5 kcal/mol) came as a surprise that, however,
correlates with the longer Ru-N1 bond (2.271 Å) in 4 com-
pared with the corresponding Ru-N1 bond in 2, 2.159 Å,
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and the diminished trans-influence reflected in the Ru-P
bond distances, 2.297 Å (4) vs. 2.305 Å (2).
results of the catalytic testing are collected in Table 3;
these include the observations of the by-product imine,
BuN=CHCH3, in the test of eq 2 (values in parentheses).
Under eq 3, Table 3 displays two values in parentheses:
the total alkene content after hydrogenation (100% when
no alkene hydrogenation) and the percentage of the C-9
alkenes, out of the total alkene content after hydrogena-
tion (0% when no C=C bond isomerization). Table 3 and
Figure 2 also include data for the Takasago catalyst
9
RuHCl(CO)[HN(CH2CH2PPh2)2]
RuHCl(CO)[PiNHCH2CH2PPh2] (12)9.
(11)8
and
our
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Figure 1. Calculated structures of 2 and the 16-electron
complex formed upon breaking the Ru-N1 bond (the C-
H hydrogens are not shown).
Table 3. Conversions and selectivities of the reac-
tions of Scheme 4 with the catalysts of Chart 1.
The reason for making complexes 2 – 10 was to test
them in the reactions of Scheme 1 to see the effect of fit-
ting the YNP catalysts with different Y-donor groups.
Three representative reactions of Scheme 4 were chosen
for the comparative testing, and we deliberately selected
demanding tests where few existing catalysts would be
expected to perform well. Specifically, very few catalysts
can convert ethanol to ethyl acetate with 0.01 mol% cata-
lyst (eq 1). For the direct synthesis of amides (eq 2), cata-
lytic efficiency at T < 100 °C and employing volatile sub-
strates (b.p. of ethanol and butylamine are near 78 °C) are
unprecedented outside our work with 1. In test eq 3, hy-
drogenation of methyl undecenoate allows assessing both
the efficiency and the selectivity of the catalysts in the
presence of a C=C bond susceptible to hydrogenation.
Low catalyst loadings in all reactions of Scheme 4 make
the overall complex stability and longevity a prerequisite
for the successful catalytic performance.
Catalyst
1a
eq 1
82
29
27
1
eq 2
eq 3
90 (0)
64 (3)
9 (3)
1 (3)
95 (98, 1)
84 (96, 2)
66 (75, 25)
5 (5, 100)
15 (5, 100)
0 (41, 23)
74 (37, 78)
69 (32, 100)
9 (31, 13)
2
3
4
5
1
8 (6)
5 (2)
34 (5)
6 (6)
2 (14)
2 (7)
5 (10)
6 (4)
6
7
0
41
41
0
8
9
10
11
12
0
11 (4, 100)
25 (86, 6)
82 (12, 100)
70
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aData from ref 7.
Scheme 4. Reactions tested in this work.
eq 1
0.01% [cat]
1% NaOEt
O
+
2H2
+
OH
HO
O
24 h, 90 °C
0.2 moles
Table 3: % conversion to ethyl acetate
eq 2
0.05% [cat]
O
1% NaOEt
N Bu
+
H2O
2H2 +
+
+
N Bu
OH
H2N Bu
17 h, 90 °C
H
0.08 + 0.08 moles
Table 3: % conversions to amide and (imine)
eq 3
0.05 mol% [cat], 50 bar H2
O
Figure 2. The vertical bars display conversions (%) to
ethyl acetate, N-butylacetamide, and the C11-alcohols,
respectively, in the reactions of Scheme 4, observed
with complexes 1 – 12.
RCH2OH + MeOH
1 mol% tBuOK, 2.5 h, 100 C
O
0.02 moles
7 ml THF
R =
or
or
or
5
5
5
5
The observations of Figure 2 and Table 3 form no trivial
pattern; we shall note the following:
Table 3: % conversion to C11ꢀalcohols, (%unsaturated, %C9 olefins)
1) The catalytic performance is profoundly influenced
by the Y group of the YNP catalysts. Among the
catalysts ineffective in the reactions of Scheme 4
are complexes 4 - 6, possessing labile Y groups, and
complexes 9 – 10 where Y is a tertiary amine.
The observed conversions to the principal products
(ethyl acetate in eq 1, N-butylacetamide in eq 2, and C11-
alcohols in eq 3) are visualized in Figure 2. The complete
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1
2) The nature of the phosphorus group most impacts
2
3
4
5
the catalytic reaction of eq 2, while being less im-
portant in eq 1 and eq 3. The results for 2 (PtBu2), 3
(PoTol2), and 12 (PPh2) suggest a need for a bulky,
good donor PR2 group for the successful amide
synthesis of eq 2.
6
7
8
9
3) The ester reduction of eq 3 is apparently the least
challenging among the catalytic reactions of
Scheme 4. Six complexes of this study afforded
good-to-high conversions to the C11-alcohols.
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4) There is no correlation between the results of the
homo- and cross-coupling of ethanol in eq 1 and 2.
Catalysts that are reasonably successful (TON >
2000) in converting ethanol to ethyl acetate can be
successful (1, 2, 7), or not (3, 8, 11, 12) in making N-
butylacetamide. Ru-MACHO complex 11 is an ex-
treme example of this disparity, affording TON =
7,000 toward ethyl acetate but only 100 turnovers
toward N-butylacetamide with additional 200
turnovers toward the imine, BuN=CHCH3.
Chart 2. Complexes 13 – 18.
At the start of this study, we did not anticipate that the
catalytic behavior of complexes 2 and 4 should turn out to
be so strikingly different. Yet, our observations correlate
with the findings of Baratta and co-workers made while
studying transfer hydrogenation of acetophenone with
the related ruthenium complexes 17 and 18, possessing -
CH2Py and –CH2CH2Py ligand groups, respectively (Chart
2).11 Baratta reported the turnover frequency with 17 an
order of magnitude greater than the corresponding TOF
value with 18. They speculated that the “five-membered
chelate ring (in 17) gives a higher stability to the six-
coordinate complex with a neat increase of its catalytic
efficiency.” Our DFT analysis of the Ru-Py bond en-
thalpies in 2 and 4 supports this explanation.
5) Complex 2 is a viable catalyst for the direct amide
synthesis as well as for the reduction of esters with
a good selectivity for C=O vs C=C bond hydrogena-
tion. However, 2 is less efficient than the osmium
analogue 1. The difference toward undec-10-enol
becomes pronounced when using 0.01 mol% cata-
lyst and 0.1 moles of the ester, without solvent.
This gave TON = 9,800 (1)7 and 5,600 (2) in 5 h un-
der p(H2) = 50 bar, with 2 mol% NaOMe, with 98-
97% retention of the C=C bond. The conversion to
N-butylacetamide was improved, from 64 to 85%
with 0.1 mol% 2, and further to 94% with 0.1 mol%
2 together with 2 mol% NaOEt (both experiments
gave < 0.5% BuN=CHMe by-product).
It is further appropriate to address the effect of the size
of the ring containing the Ru-P bond in 2 - 12. Figure 3
displays the DFT structure of 2 together with the DFT
structures of RuHCl(CO)[PiNHCH2CH2CH2PtBu2] (2a)
and RuHCl(CO)[PiNHCH2CH2PtBu2] (2b). Complex 2a
possesses a six-atom ruthenacycle that is the largest (10.93
Å) in the series, followed by 2 (10.70 Å) and 2b (9.37 Å, as
the sum of the bonds forming the metallacycle). The Ru-
P, Ru-N2 distances, and the Ru-N1 bond enthalpy follow
the same trend: 2a possesses the longest Ru-P (2.317 Å)
and Ru-N2 (2.246 Å) bonds and the strongest Ru-N1 bond
(19.5 kcal/mol). The relatively weak Ru-N1 bond in 2b
(16.3 kcal/mol) is similar to that of the related complex 12
(17.9 kcal/mol). One can attribute the deteriorated (12%
vs. 96%) selectivity in eq 3 with 12 vs. 2 to the increased
lability of the Ru-N1 bond in 12 and formation of η2-alkene
ruthenium hydride intermediates, leading to the C=C
bond hydrogenation and isomerization. Overall, com-
plexes possessing fused 5+6 atom metallacycles of the κ3-
YNP, especially 1 and 2, appear to be best-balanced in
terms of stability. We should note, however, the relatively
long M-N2 bonds of 2 and 2a in Figure 3. Thus, if the M-Y
bond is weak (as in 4 - 6) the loss of both Ru-Y and Ru-N2
bonds of the κ3-YNP ligands becomes a distinct possibility
at 80 – 100 °C that might lead to catalyst degradation.
6) The overall most successful ruthenium catalyst af-
ter 2 is 7, however the decent efficiency of 7 toward
ethyl acetate is offset by the reduced efficiencies
and
butylacetamide and undec-10-enol.
Discussion
Xu and
especially
selectivities
toward
N-
Langer
recently
tested
our
RuCl2(PPh3)[PiNHCH2CH2PPh2] (13) catalyst and the re-
lated complexes 14 - 16 of Chart 2 in the acceptorless de-
hydrogenative coupling of benzyl alcohol.10 Their experi-
ments gave 1210 (13), 52 (14), 140 (15), and 20 (16) turno-
vers to benzyl benzoate. This and other observations of
Xu and Langer suggested, in the words of the authors,
that “with the weakening ruthenium–heteroatom bond
the catalytic activity of these ruthenium pre-catalysts in
the acceptorless dehydrogenation of primary alcohols as
well as the hydrogenation of ketones is diminished.” The
weakly-bonded complexes 4, 5, and 6 in our work are sim-
ilarly inefficient. It is clear that structural changes result-
ing in increased ligand lability offer no benefits in the
catalytic reactions of Scheme 1.
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Figure 3. DFT (M06-L) parameters of complexes 2 – 2b.
Scheme 5. Dehydrogenative coupling of ethanol.a
Reactions of Schemes 1 and 4 can follow two broadly
defined mechanisms A and B, the key difference being the
presence of free organic intermediates in A and the ab-
sence of these in B. We have discussed mechanism B in
recent papers.7, 13 Mechanism A for ethanol dehydrogena-
tion of eq 1 is illustrated in Scheme 5. We calculated M06-
L free energies of 21 - 25 and TS1 – TS4 for M = Os and the
corresponding species originating from 1.
NaOEt
L
LnM
Cl
NR2
H
nM NR2
H
O
ꢀNaCl
Et
20
LnM NR2
19
Pre-catalyst
1
is converted into the ethoxide
L
nM NR2
OsH(OEt)(CO)[PiNHCH2CH2NHPtBu2] (20) upon treat-
ment with NaOEt in ethanol; then acetaldehyde is pro-
duced via the anagostic intermediate 21 and TS1. Follow-
ing the ideas of Hasanayn,5d,e,6a acetaldehyde can couple
with the ethoxide 20 in an outer-sphere fashion via TS2,
leading to 23. Intermediate 23 can rearrange into 1-
ethoxyethanolate 25 or (via the “hemiacetaloxide slip-
page” TS3) directly to the anagostic complex 24 and ulti-
mately to the dihydride 22 and ethyl acetate.
H
H
C
O
Me
TS1
: 13.6
H
21
: 9.0
O
L
nM
NR2
H
LnM
H
NR2
EtOH
20
Et O
H
H
The ethoxide 20 is regenerated in ethanol from 22; the
details of this process are elaborated in Scheme 6 follow-
ing the ideas of Dub and Gordon proposed for the related
bifunctional catalysts.12 Thus, we adopted the view of
Gordon et al that the “amido complex … is not an inter-
mediate within the catalytic cycle” when interpreting the
events leading from 22 to 20.12a
22
C
O
H2
Me
TS2
: 18.6
EtOAc
TS4
: 18.4
L
nM
NR2
Scheme 6. Formation of 20 from 22 and EtOH.
H
O
Et O
L
nM
NR2
TS3
: 20.6
C
H
H
(hemiacetaloxide slippage)
H
C
Me
23: 17.6
O
Me
LnM NR2
H
C
OEt
24
H
O
The ethoxide 20 must be the principal species in etha-
nol according to DFT (ΔG = -1.9 kcal/mol vs. 19 and
EtOH). However, since the DFT modelling does not take
into account hydrogen bonding of ethanol, formation of
20 is expected to be less favorable in experiment than in
theory.
: 18.9
OEt
Me
25
: 9.3
aThe origin of the energies (kcal/mol, in ethanol solvent, at
298.15 K) is species 20 with EtOH. Mass balance is insured in
the entire scheme.
Both osmium ethoxide 20 and 1-ethoxyethanolate 25
have been documented by ESI MS in ethanol dehydro-
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genation to ethyl acetate catalyzed by 1 with NaOEt.13
entropy-controlled. Our findings are contrary to the as-
1
2
3
4
5
6
7
8
9
Furthermore, the collision-induced dissociation (CID)
experiments demonstrated formation of acetaldehyde
from 20, and ethyl acetate from 25 in the gas phase.13 It is
important to emphasize that amide 19 in Scheme 5 is an
off-cycle transient species when ethanol is abundant, so
short-lived by rapidly adding EtOH that it could not be
detected by ESI MS.
sessment that “a Tishchenko-type disproportionation”
was not operative with the Milstein dearomatized cata-
lyst.1a
The events of Scheme 5 are rearranged into a simplified
catalytic cycle for the hydrogenation of a methyl ester in
Scheme 8. It is understood that the intermediate aldehyde
RCHO (from step III) is independently hydrogenated by
the catalyst to RCH2OH. For example, the dihydride
OsH2(CO)[PiNHCH2CH2NHPtBu2] (22) (0.05 mol%) gave
730 turnovers of neat methyl acetate to ethanol in 1 h at
room temperature, under p(H2) = 50 bar.7 This example
illustrates that the catalytic reduction of unactivated es-
ters can be fast without heating or added base. A subtle
point omitted in Scheme 8 is the possibility of formation
of the [M]OCH2R alkoxide in the reaction solution. If this
alkoxide re-combines with the aldehyde RCHO, this
should lead to the symmetrical ester. Indeed, in the cata-
lytic reaction mentioned above (interrupted at 1 h), 5.4%
of methyl acetate converted to ethyl acetate. In our expe-
rience, seeing small amounts of symmetrical esters is
common in the catalytic ester hydrogenation reactions.
Based on the experimental data, ΔG = 13.2 kcal/mol for
ethanol dehydrogenation to acetaldehyde at 25 °C.14 Com-
bining this with the calculated reaction energy for 19 + H2
→ 22, ΔG = -2.5 kcal/mol (Scheme 7) suggests that for-
mation of acetaldehyde and 22 from 19 and ethanol is
unfavorable by ΔG = 10.7 kcal/mol. Considering the asso-
ciated equilibrium constant K = 2.3∙10-7 and the osmium
concentration [Os] = 1.7∙10-3 M, it is not surprising that
acetaldehyde has never been observed by NMR in the
catalytic studies in our group. Formation of acetaldehyde
is even less favorable on Ru where the reaction free ener-
gy ΔG = 11.6 kcal/mol, based on the data of Scheme 7.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
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Scheme 7. Formation of acetaldehyde.a
Scheme 8. Catalytic ester hydrogenation.
H2
Exp.: ∆H = 19.4 kcal/mol, ∆G = 13.2 kcal/mol
+
OH
O
tBu2
N P
H
tBu2
N P
H
H
H
CO
N
CO
N
M
M
+
H2
N
N
H
H
DFT, M = Os: ∆H = ꢀ12.7 kcal/mol, ∆G = ꢀ2.5 kcal/mol
DFT, M = Ru: ∆H = ꢀ11.8 kcal/mol, ∆G = ꢀ1.6 kcal/mol
aThe calculated M06-L data are in EtOH, at 298.15 K.
To gain more information, we investigated the reaction
of the osmium dihydride 22 with acetaldehyde, expected
to produce the ethoxide 20 by insertion. With 25 equiva-
lents of acetaldehyde, this experiment quantitatively con-
verted the aldehyde into ethyl acetate upon mixing in
ethanol. Acetaldehyde (4.7 M) also reacted quantitatively
in benzene-d6, with 0.25 mol% 22. Decreasing the catalyst
loading to 0.1 mol% in benzene-d6 gave TON = 930 to
Catalytic cycles similar to Scheme 8 have been pro-
posed and discussed by others (Morris,5f Hasanayn5d,e, 6a
)
and also proposed by Yang5a for the “SNS” catalyst16 from
our group, RuCl2(PPh3)[HN(CH2CH2SEt)2]. With the lat-
1
ethyl acetate, according to the H NMR spectrum record-
ed in 8 min after mixing (TOF ≥ 7000 h-1). Thus, the dihy-
dride 22 is a highly efficient catalyst for the Tishchenko
reaction where the C-O bond of the ester forms in an out-
er-sphere fashion via TS2.15 One should note that the re-
action of 22 with acetaldehyde did not follow the “bifunc-
ter,
the
ethoxide
RuH(OEt)(PPh3)[HN(CH2CH2SEt)2]∙EtOH gave the dihy-
dride RuH2(PPh3)[HN(CH2CH2SEt)2], ethyl acetate, and
H2 upon heating in toluene (Scheme 9),16 again highlight-
ing the key role of the alkoxides in the catalytic reactions
of Schemes 5 and 8.
tional double hydrogen transfer" (BDHT) pathway dis-
4b, 5c, g, 6e,g
cussed in the recent literature,3a,
that should
have resulted in a stoichiometric formation of ethanol
together with the amide 19.
The enthalpy and free energy of TS2 vs. 20 and acetal-
dehyde are 1.6 and 12.8 kcal/mol, respectively, and TS3 is
only marginally higher: ΔH‡ = 3.9 and ΔG‡ = 14.8
kcal/mol; hence the Tishchenko reaction is effectively
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Scheme 9. Formation of ethyl acetate from the “SNS”
ethoxide.
at 80 °C. Heating a 2000:2000:1 mixture of EtOH/BuNH2
with the dihydride 22 produced N-butylacetamide: TON =
93 (0.5 h) and 127 (1 h); a trace of ethyl acetate was detect-
able. Without the catalyst, 1-13C-ethyl acetate
(Me13COOEt) in EtOH/BuNH2 (100:2000:2000), gave 3
(0.5 h) and 6 (1 h) turnovers to N-butyl-1-13C-acetamide.
Finally, an experiment with 22, 1-13C-ethyl acetate and
EtOH/BuNH2 (1:100:2000:2000) produced TON = 99 (0.5
h) and 134 (1 h) toward N-butylacetamide, while consum-
ing 48% (0.5 h) and 65% (1 h) of 1-13C-ethyl acetate. There
was 91% 12C=O in the product amide in 0.5 h and 90% in 1
h, whereas the 13CH2 content of ethanol increased to 2.9%
in 0.5 h and to 3.8% in 1 h. Thus most product of eq 2
originates directly from ethanol, whereas ethyl acetate is
hydrogenated during the amide synthesis and, perhaps
for this reason, does not accumulate in the reaction.
Crabtree and Eisenstein suggested6i in 2010 that “for
amide to be formed, the hemiaminal must remain metal-
bound.” In this context, we shall discuss one plausible
scenario for mechanism B where the entire catalytic cycle
occurs in the coordination sphere of the same metal cen-
ter. The MLn → MLn-1 events of Scheme 11 stand for the
reversible loss of one M-L bond and opening of a vacant
coordination site, for example from 20 to 27. The calcu-
lated free energies of 27 - 34 and TS5 – TS7 are for M = Os
and the corresponding osmium species originating from 1.
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Through the rest of this discussion we should look at
the catalytic chemistry of eq 2 of Scheme 4 with the focus
on the selectivity of this reaction which is peculiar. In our
hands, deliberately reacting acetaldehyde with butyla-
mine in ethanol produced the imine upon mixing. A gas-
phase kinetic study of neopentanal with methylamine
gave ΔH‡ = 9.0 kcal/mol and ΔS‡ = −70.6 eu/mol for
294
294
the formation of N-(neopentylidene)methanamine.17 The
authors concluded that the numbers were “suggestive of a
very highly ordered transition state” and the imine for-
mation was catalyzed by the glass surface of the cell.17 In a
reaction that is entropy-controlled, the barrier is signifi-
cantly reduced in the condensed phase. For example, our
M06-2X/def2TZVP calculations in ethanol gave ΔG‡
=
298
20.6 kcal/mol (ΔH‡
= 12.8 kcal/mol, ΔS‡
= −26.1
298
298
eu/mol for the dehydration of 1-(methylamino)ethanol,
assisted by two hydrogen-bonded molecules of ethanol.
Thus imine formation can be fast and is a real concern in
the amide synthesis of eq 2 with the catalysts capable of
producing free aldehyde.
The catalytic cycle starts by elimination of the hemila-
bile Y = Pi group from the ethoxide 20, followed by the
classical β-H elimination via the agostic complex 28 and
TS5 to give the metal-bonded acetaldehyde of 29. The
latter is attacked by the amine to give the zwitterion 30.
The path from 20 to 30 is slightly higher in energy com-
pared to the ethyl acetate synthesis of Scheme 5, however,
energies up to 25 kcal/mol should not be prohibitive in
refluxing ethanol. Furthermore, ωB97X-D calculations on
four selected species of Scheme 11 suggest that the rate-
determining steps of Scheme 11 could be overestimated by
M06-L, assuming that the ωB97X-D functional is more
accurate for transition states and TS-like intermediates. It
can be claimed with sufficient confidence that the amide
bond formation leading to 30 is a feasible process.
The catalytic mechanism of Scheme 5 is problematic for
the amide synthesis of eq 2. The osmium ethoxide 20 is
considerably more stable than the amide 26 in Scheme 10.
Since 26 is practically non-existent, efficient formation of
the amide bond by coupling 26 with the transient acetal-
dehyde is unrealistic. The scenario of the intermediate
hemiaminal dehydrogenation in the “bifunctional double
4b, 5c, g, 6e,g
hydrogen transfer" (BDHT) fashion,3a,
is also
questionable since the 16-e amido complex 19 has not
been detected in ethanol or ethanol/amine mixtures and
the BDHT pathway clearly does not operate in the related
catalytic ester synthesis of Scheme 5.
From 30, the ensuing events leading to 31 are less clear
and are challenging to model since the reaction of eq 2
takes place without solvent and all catalytic intermediates
are solvated by the substrates, ethanol and the amine.
Computationally, adding an explicit molecule of EtOH to
30 works to increase the free energy from 24.4 to 28.1
kcal/mol. This increase is entirely due to the TΔS term
and would have made sense in a bimolecular process
where the molecules reacted through solvent, that is obvi-
ously not the case here. It is worth adding that the free
energy of 30 itself already includes the likely exaggerated
entropy cost of 9.5 kcal/mol of bringing MeNH2 to 29.
Another point that is open to consideration is the possi-
bility that 30 might be acidic enough to be deprotonated
by the basic amine substrate, affording an anionic hydride
intermediate further protonated by ethanol to give 31,
bypassing TS6.
Scheme 10. Formation of amide 26 (M06-L data in
EtOH at 298.15 K).
To assess the possibility of a two-step mechanism
where ethanol is first converted into ethyl acetate and the
latter reacts with butylamine to give the final amide
product of eq 2, we ran a series of NMR tube reactions, all
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thermore, the collision-induced dissociation (CID) exper-
2
3
4
5
6
7
8
9
iment demonstrated formation of N-butyl acetamide from
the 1-(butylamino)ethanolate intermediate in the gas
phase. For this reason, even though the calculated free
energy of TS6 appears to be high for a reaction producing
TON > 100 h-1 we believe it is best to consider the mecha-
nism of Scheme 11 until an efficient catalyst for the amide
synthesis of eq 2 is found that would possess no hemila-
bile group.
Scheme 11. Catalytic formation of N-methyl acetam-
ide.a
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Conclusions
Several observations and conclusions of this paper can
be summarized as follows.
1) The catalytic reactions represented by Scheme 1
superficially suggest a common mechanism. For
example, it may seem that the success of both the
ester synthesis and the amide synthesis should de-
pend on the ability of the catalyst to dehydrogen-
ate the alcohol. In practice, there is a disconnect
between the two reactions, and the catalytic effi-
ciency in the ester synthesis does not correlate
with the efficiency in the amide synthesis. There-
fore, catalysts highly active in both homo- and
cross-coupling of primary alcohols as well as in the
hydrogenation of the carbonyls may be rare com-
pounds able to exploit the outer-sphere and inner-
sphere pathways of Schemes 5, 7, and 10 similarly
well.
2) Some practical advice can be offered for future cat-
alyst design. Overall catalyst stability is a prime
concern, and our preference is to work with ther-
mally robust systems. The stability of metal com-
plexes often follows the trend 5d > 4d > 3d, there-
fore developing 3d metal catalysts for the reactions
of Scheme 1 should be most challenging, whereas
the use of 5d metals can be advantageous.
3) Related to point 2 above, the use of polydentate
ligands can be recommended and weakly-bonded
groups should be avoided. For example, pincer lig-
ands forming 6+5 metallacycles (with a phospho-
rus donor in the 6-atom ring) are a suitable choice.
It remains unclear why complexes 9 and 10, where
Y = tertiary amine, proved to be inactive in our
work; however, this experience suggests a certain
caution toward the use of such groups.
4) All existing successful catalysts for the reactions of
Scheme 1 possess at least one good donor group,
typically a phosphorus group. Since the use of a
bulky donor group seems advantageous for the am-
ide synthesis, the other donor groups around the
metal should be sterically less demanding (small or
flat), to keep access to the metal as open as possi-
ble.
aThe origin of the M06-L energies (kcal/mol, in ethanol
solvent, at 298.15 K) is species 20 with MeNH2. Mass balance
is insured in the entire scheme. Values in parentheses are
free energies from ωB97X-D calculations.
Following H2 elimination from 31 and re-coordination
of the Y group in the hemiaminaloxide 33, the catalytic
cycle is completed by hydride elimination in 34 producing
N-methyl acetamide in a fashion analogous to the ethyl
acetate formation from intermediate 24 in Scheme 5. The
1-(butylamino)ethanolate intermediate analogous to 33
was detected by ESI MS in the dehydrogenative coupling
reaction of ethanol with butylamine catalyzed by 1.13 Fur-
5) An N-H, as part of a polydentate ligand, is an im-
portant directing group in the catalytic reactions of
Scheme 1, via hydrogen bonding to the substrates.
There are other strategies, e.g. the classical
dearomatized Milstein catalyst does not possess an
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N-H group. In practice, there is no reason for not
QuiCH2NH(CH2)2NH2
quinolyl)methyl)ethylenediamine, QuiNN).
(N-((2-
250-mL
using the “N-H effect” in the catalytic reactions of
Scheme 1, and designing ligands built around an N-
H functionality is arguably the more simple ap-
proach that has been already exploited in a large
number of existing bifunctional Noyori-type cata-
lysts.
A
round-bottom flask equipped with a stir bar was charged
with ethylenediamine (33 g, 0.9 mol), then 2-
(chloromethyl)quinoline hydrochloride (25 g, 89.9 mmol)
was added in four portions over a 1 h period with stirring,
and the mixture was left stirring overnight. 70 mL of Et2O
was added and after vigorous shaking the top layer was
decanted. The bottom layer was additionally extracted
with 2 × 70 mL of Et2O, while decanting the top layer. The
combined ether extract was evaporated under vacuum
(one should be prepared to see ethylenediamine freezing,
m.p. 8 °C). The product was isolated by vacuum distilla-
tion. First, ethylenediamine was condensed into a flask
immersed into an ice bath. Then the distillation apparatus
was fitted with a cow type receiver and the product boil-
ing at 140 - 148 °C (p = 0.01 torr) was collected. The distil-
lation was complicated by decomposition and only a
small amount of the product was recovered, contaminat-
ed with 8-9 mol% of 2-methylquinoline. Yield: 4.1 g (ca
Experimental
Unless mentioned otherwise, the manipulations were
performed under argon. The NMR spectra were recorded
on an Agilent DD2 400 MHz and Varian Unity Inova 300
MHz spectrometers. All 31P chemical shifts are indirectly
11
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1
13
referenced to external 85% H3PO4. The H and C chemi-
cal shifts are relative to the residual deuterated solvent
peaks. The spin-spin coupling constants, J, are reported in
Hz. RuCl3∙nH2O was purchased from Pressure Chemicals
and Ru-MACHO was obtained from Strem. 1-13C-ethyl
acetate was supplied by Cambridge Isotope Laboratories
All other chemicals and anhydrous grade solvents were
purchased from Aldrich. Methyl 10-undecenoate and bu-
tylamine were treated by passing them through activated
basic alumina and stored under argon; anhydrous ethanol
was stored over 3 Å molecular sieves under argon.
[RuCl2(COD)]n and PyCH2NH(CH2)2NH2 were prepared
following previously reported methods7, 18 The NMR spec-
tra were analyzed with the help of the iNMR Reader that
also allowed deconvolution of the lines of N-butyl acet-
amide and N-butyl 1-13C-acetamide to quantify their con-
tributions.
1
17%) of a viscous liquid. H NMR (benzene-d6): δ 8.19 (d,
J=8.8, 1H, CH), 7.55 (d, J=8.4, 1H, CH), 7.38 (d, J=8.0, 1H,
CH), 7.31 (m, 1H, CH), 7.17 (d, J=8.4, 1H, CH), 7.11 (m, 1H,
CH), 3.93 (s, 2H, CH2), 2.51 (m, 2H, CH2), 2.46 (m, 2H,
CH2), 0.85 (br s, 3H, NH + NH2). 13C{1H} NMR (benzene-
d6): δ 162.02 (s), 148.86 (s), 136.29 (s), 130.11 (s), 129.74 (s),
128.10 (s), 127.99 (s), 126.30 (s), 121.03 (s), 56.60 (s, CH2),
53.30 (s, CH2), 42.77 (s, CH2).
MeO(CH2)2NH(CH2)2NH2
(N-(2-
methoxyethyl)ethylenediamine, ONN). A 250-mL round-
bottom flask equipped with a stir bar was charged with
ethylenediamine (75 g, 1.248 mol), then 2-bromoethyl
methyl ether (25 g, 0.18 mol) was added in portions over
25 min with stirring (Note: although the reaction solution
becomes hot, it does not require external cooling). In 1.5 h
(when the reaction solution cooled to room temperature),
100 mL of Et2O was added. A two-phase system formed
upon stirring. The bottom layer was removed with a pi-
pette, and the upper ether solution was evaporated under
vacuum (one should be prepared to see ethylenediamine
freezing, m.p. 8 °C). The remaining mixture of the prod-
uct and ethylenediamine was separated by vacuum distil-
lation. First, ethylenediamine was collected into a flask
immersed into an ice bath (b.p. near r.t. under 2 torr, bath
at 45 °C). Then the distillation apparatus was fitted with a
cow type receiver and the product distilled (b.p. ca. 50 °C,
2 torr) as a clear colorless liquid. Yield: 11.53 g (54%). It is
likely that a better yield could be obtained if the bottom
layer (see above) was extracted with a second 100 mL por-
Syntheses
Py(CH2)2NH(CH2)2NH2
(N-((2-
picolyl)methyl)ethylenediamine, PiCH2NN). A 100-mL
round-bottom flask containing a stir bar was charged with
ethylenediamine (33 g, 0.549 mol), then 2-(2-
chloroethyl)pyridine (13 g, 91.8 mmol) was added with
stirring, and the mixture was left stirring overnight to give
a 4:1 mixture of PiCH2NN and 2-vinylpyridine (identified
by NMR). 70 mL of Et2O was added and after vigorous
shaking the top layer was decanted. The bottom layer was
additionally extracted with 2 × 70 mL of Et2O, while de-
canting the top layer. The combined ether extract was
evaporated under vacuum (one should be prepared to see
ethylenediamine freezing, m.p. 8 °C). The product was
isolated by vacuum distillation. First, ethylenediamine
and 2-vinylpyridine were condensed into a flask im-
mersed into an ice bath. Then the distillation apparatus
was fitted with a cow type receiver and the product boil-
ing at 96 - 102 °C (p = 0.05 torr, bath at 135 °C) was col-
1
1
lected. Yield: 9.0 g (59%) of a viscous liquid. H NMR
tion of Et2O. H NMR (benzene-d6): δ 3.27 (t, J=5.3, 2H,
(benzene-d6): δ 8.48 (m, 1H, Py), 7.06 (td, J=7.6, 2.0, 1H,
Py), 6.80 (d, J=7.6, 1H, Py), 6.63 (m, 1H, Py), 2.98 (m, 2H,
CH2), 2.89 (m, 2H, CH2), 2.54 (m, 2H, CH2), 2.46 (m, 2H,
CH2), 0.85 (br s, 3H, NH + NH2). 13C{1H} NMR (benzene-
d6): δ 161.71 (s, Py), 150.02 (s, Py), 136.07 (s, Py), 123.52 (s,
Py), 121.33 (s, Py), 53.41 (s, CH2), 49.99 (s, CH2), 42.75 (s,
CH2), 39.50 (s, CH2).
OCH2), 3.08 (s, 3H, OCH3), 2.62 (t, J=5.3, 2H, CH2), 2.55
(m, 2H, CH2), 2.44 (m, 2H, CH2), 0.98 (br, 3H, NH + NH2).
13C{1H} NMR (benzene-d6): δ 73.06 (s, OCH2), 58.81 (s,
OCH3), 53.58 (s, CH2), 50.03 (s, CH2), 42.78 (s, CH2).
EtS(CH2)2NH(CH2)2NH2
(ethylthio)ethyl)ethylenediamine, SNN).
round-bottom flask equipped with a stir bar was charged
with ethylenediamine (85 g, 1.414 mol), then 2-chloroethyl
(N-(2-
250-mL
A
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ethyl sulfide (25.3 g, 0.20 mol) was added with stirring,
canted. The bottom layer was additionally extracted with
2
3
4
5
6
7
8
9
and the mixture was left stirring overnight. The product
was extracted twice with Et2O (2 ×100 mL), while decant-
ing the top ether layer. The combined ether extract was
evaporated under vacuum (one should be prepared to see
ethylenediamine freezing, m.p. 8 °C). The remaining mix-
ture of the product and ethylenediamine was separated by
vacuum distillation. First, ethylenediamine was collected
into a flask immersed into an ice bath (boiling near r.t.
under 2 torr, bath at 45 °C). Then the distillation appa-
ratus was fitted with a cow-type receiver and the product
boiling between 55 and 70 °C under vacuum of an oil
pump (p = 0.01 torr) was collected. Yield: 25.07 g (83%) of
2 × 70 mL of Et2O, while decanting the top layer. The
combined ether extract was evaporated under vacuum
(one should be prepared to see ethylenediamine freezing,
m.p. 8 °C). The remaining mixture of the product and
ethylenediamine was separated by vacuum distillation.
First, ethylenediamine was collected into a flask im-
mersed into an ice bath (boiling near r.t. under 3 torr,
bath at 45 °C). Then the distillation apparatus was fitted
with a cow-type receiver and, after collecting a small fore-
ran (10 drops), the product boiling between 58 and 60 °C
(p = 0.01 torr) was collected. Yield: 18.29 g (79%) of a clear
colorless liquid. 1H NMR (benzene-d6): δ 2.65 (t, J=6.4, 2H,
CH2), 2.60 (m, 2H, CH2), 2.52 (overlapped m, 4H, 2 ×
CH2), 2.36 (m, 4H, 2 × CH2), 1.57 (m, 4H, 2 × CH2), 0.99
(br, 3H, NH + NH2). 13C{1H} NMR (benzene-d6): δ 56.85 (s,
CH2), 54.70 (s, 2 × CH2), 53.84 (s, CH2), 49.44 (s, CH2),
42.90 (s, CH2), 24.27 (s, 2 × CH2).
10
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19
20
21
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23
24
25
26
27
28
29
30
31
32
33
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45
46
47
48
49
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a clear colorless liquid. H NMR (benzene-d6): δ 2.62 (m,
2H), 2.54 (m, 2H, CH2), 2.47 (m, 2H, CH2), 2.40 (m, 2H,
CH2), 2.27 (q, J=7.6, 2H, SCH2), 1.06 (t, J=7.6, 3H, CH3),
0.88 (br, 3H, NH + NH2). 13C{1H} NMR (benzene-d6): δ
53.06 (s, CH2), 49.63 (s, CH2), 42.73 (s, CH2), 32.86 (s,
SCH2), 26.32 (s, CH2), 15.48 (s, CH3).
PiNH(CH2)2NHP(o-Tol)2 (PiNP-oTol). (o-Tol)2PCl (5.14
g, 20.7 mmol) was added to a rapidly stirred solution of
PiNH(CH2)2NH2 (6.25 g, 41.3 mmol) in THF (50 mL). The
resulting mixture was rapidly stirred for 30 min. The sol-
ids were filtered, and the filtrate was evaporated and
dried under vacuum to give a very viscous liquid (7.414 g,
98.7%). The isolated material was a 95:5 mixture of the
product PiNP-oTol and the diphosphine, PiN(P(o-
Tol)2)(CH2)2NHP(o-Tol)2 (31P δ 51.1, 25.2 (s)), also contain-
Me2N(CH2)2NH(CH2)2NH2
(N-(2-
(dimethylamino)ethyl)ethylenediamine, Me2NNN).
A
300-mL round-bottom flask equipped with a stir bar was
charged with 2-chloro-N,N-dimethylethylamine hydro-
chloride (30 g, 0.208 mol), then ethylenediamine (100 g,
1.66 mol) was added with stirring, and the mixture was
left stirring for 2 h (Note: the flask becomes hot, however
no external cooling was used as ethylenediamine appar-
ently did not boil). Addition of ca. 70 mL of Et2O gave a
two-phase system upon stirring. The top layer was de-
canted, and the bottom layer was additionally extracted
with 2 × 70 mL of Et2O while decanting the top layer. The
combined ether extract was evaporated under vacuum
(one should be prepared to see ethylenediamine freezing,
m.p. 8 °C). The remaining mixture of the product and
ethylenediamine was separated by vacuum distillation.
First, ethylenediamine was collected into a flask im-
mersed into an ice bath (boiling near r.t. under 2 torr,
bath at 45 °C). Then the distillation apparatus was fitted
with a cow-type receiver. After collecting a small foreran
(1.58 g), the product boiling between 63 and 65 °C (p = 2
torr) was collected. Yield: 19.55 g (71.5%) of a clear color-
31
ing minor impurities at P δ 14.7 (2.3%) and −36.9 (1.9%).
Smaller chlorides, e.g. ClPPh2 react at both NH and NH2
1
groups of PiNH(CH2)2NH2 with similar rates. H NMR
(benzene-d6) δ 8.46 (ddd, J=4.8, 1.6, 0.8, 1H, Py), 7.37
(overlapped m, 2H), 7.07 (overlapped m, 7H), 6.96 (d,
J=7.79, 1H, Py), 6.64 (m, 1H, Py), 3.75 (s, 2H, CH2), 2.89
(dq, J=8.6, 6.0, 2H, CH2), 2.46 (t, J=5.8, 2H, CH2), 2.44 (s,
13
6H, CH3), 1.96 (br m, 1H, NH), 1.75 (br s, 1H, NH). C{1H}
NMR (benzene-d6) δ 161.36 (s, Py), 149.76 (s, Py), 141.61 (d,
J=26.0), 140.15 (d, J=13.5), 136.16 (s, Py), 131.06 (d, J=2.6),
130.77 (d, J=4.0), 129.07 (s), 126.47 (d, J=0.8), 122.21 (s, Py),
121.94 (s, Py), 55.67 (s, CH2), 51.95 (d, J=6.4, CH2), 47.32 (d,
J=17.0, CH2), 21.25 (d, J=20.6, CH3). 31P{1H} NMR (benzene-
d6) δ 25.6 (s).
1
less liquid. H NMR (benzene-d6): δ 2.59, 2.56 (over-
PiCH2NH(CH2)2NHPtBu2 (PiCH2NP).
A
200-mL
lapped, 4H, 2CH2), 2.49 (m, 2H, CH2), 2.28 (t, J=6.0, 2H,
round-bottom flask equipped with a stir bar was charged
with N-((2-picolyl)methyl)ethylenediamine (PiCH2NN)
(8.96 g, 54.22 mmol), triethylamine (6.6 g, 65.22 mmol),
and THF (50 mL). Then tBu2PCl (9.79 g, 54.19 mmol) was
added with stirring, and the mixture was left stirring rap-
idly for 24 h. The precipitated Et3N∙HCl was vacuum-
filtered and washed with 2 × 10 ml THF. The filtrate was
evaporated under vacuum. Hexane (20 mL) was added
and the mixture was filtered through 10 g of basic alumina
in a 30 mL fritted funnel; the solids were washed with 10
mL of hexane and 10 mL of Et2O. The volatiles were evap-
orated and the product was dried under vacuum at 70 °C
for 1 h. Yield: 15.72 g (94%) of a viscous liquid. The prod-
13
CH2), 2.05 (s, 6H, NMe), 0.98 (br, 3H, NH + NH2). C{1H}
NMR (benzene-d6): δ 60.10 (s, CH2), 53.78 (s, CH2), 48.18
(s, CH2), 45.92 (s, NMe), 42.89 (s, CH2).
c-C4H8N(CH2)2NH(CH2)2NH2
yl)ethyl)ethylenediamine, PyrNN).
(N-(2-(pyrrolidin-1-
A 300-mL round-
bottom flask equipped with a stir bar was charged with 1-
(2-chloroethyl)pyrrolidine hydrochloride (25 g, 0.147
mol), then ethylenediamine (71 g, 1.18 mol) was added and
the mixture was stirred for 3 h, affording a two-layer sys-
tem where the upper dark layer contained the product
and ethylenediamine in a 2:3 ratio, whereas the bottom
yellow layer had the two species in a 1:21 ratio, respective-
ly. The reaction appeared to be finished at that time. The
mixture was left stirring overnight. 70 mL of Et2O was
added and after vigorous shaking the top layer was de-
1
uct was ca. 98% pure according to 31P NMR. H NMR
(benzene-d6): δ 8.48 (m, 1H, Py), 7.07 (td, J=7.6, 2.0, 1H,
Py), 6.79 (d, J=7.6, 1H, Py), 6.64 (m, 1H, Py), 3.02 (over-
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lapped m, 4H, 2 × CH2), 2.91 (t, J=6.0, 2H, CH2), 2.60 (t,
stirring, and the mixture was left rapidly stirring for 17 h.
The precipitated Et3N∙HCl was vacuum-filtered and
washed with 2 × 10 ml THF. The filtered solution was
evaporated under vacuum, and the product was isolated
by distillation. A small forerun was collected (60 – 93 °C,
0.71 g, bath at 140 °), then the main fraction (93 - 129 °C, p
< 0.01 torr, bath at 150 to 160 °C, 18.77 g (95%)) as a clear
colorless, slightly viscous liquid. The product was >98%
pure by 31P NMR. 1H NMR (benzene-d6): δ 3.01 (ddt, J=8.0,
6.4, 5.9, 2H, CH2), 2.64 (t, J=6.6, 2H, CH2), 2.54 (t, J = 5.9,
2H, CH2), 2.48 (t, J=6.6, 2H, SCH2), 2.27 (q, J=7.3, 2H,
SCH2), 1.49 (br. m, 1H, NH), 1.25 (s, 1H, NH), 1.09 (d, J=11.2,
18H, CH3), 1.06 (t, J=7.3, 3H, CH3). 13C{1H} NMR (benzene-
d6) δ 52.45 (d, J=6.9, CH2), 50.81 (d, J=28.7, CH2), 49.27 (s,
CH2), 34.44 (d, J=21.5, C), 32.93 (s, SCH2), 28.90 (d, J=15.3,
CH3), 26.28 (s, SCH2), 15.45 (s, CH3). 31P{1H} NMR (ben-
zene-d6): δ 77.9 (s).
J=5.8, 2H, CH2), 1.62 (br s, H, NH), 1.52 (br m, 1H, NH),
1.07 (d, J=11.2, 18H, CH3). 13C{1H} NMR (benzene-d6) δ
161.60 (s, Py), 150.02 (s, Py), 136.09 (s, Py), 123.58 (s, Py),
121.35 (s, Py), 52.76 (d, J=7.1, CH2), 50.77 (d, J=29.0, CH2),
49.70 (s, CH2), 39.26 (s, CH2), 34.41 (d, J=21.5, C), 28.90 (d,
J=15.2, CH3). 31P{1H} NMR (benzene-d6): δ 77.9 (s).
QuiCH2NH(CH2)2NHPtBu2 (QuiNP). A 100-mL round-
bottom flask equipped with a stir bar was charged with N-
((2-quinolyl)methyl)ethylenediamine (QuiNN) (3.97 g, ca.
19 mmol), triethylamine (2.4 g, 23.71 mmol), and THF (22
mL). Then tBu2PCl (3.5 g, 19.37 mmol) was added with
stirring, and the mixture was left stirring rapidly for 24 h.
The precipitated Et3N∙HCl was vacuum-filtered and
washed with 3 × 3 ml THF. The filtered solution was
evaporated under vacuum. Hexane (20 mL) was added
and the mixture was filtered through 10 g of basic alumina
in a 30 mL fritted funnel; the solids were washed with 5
mL of hexane. The volatiles were evaporated and the
product was dried under vacuum at 70 °C for 1 h. Yield:
5.57 g of a viscous liquid. The product was obtained con-
taminated with ca. 12 mol% of 2-methylquinoline (the
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H2N(CH2)2NH(CH2)2NHPtBu2 (H2NNP).
A 200-mL
round-bottom flask equipped with a stir bar was charged
with diethylenetriamine (40 g, 0.388 mol) and tBu2PCl (10
g, 0.055 mmol) was added over 10 min with stirring. In 20
min, 50 mL of Et2O was added and the mixture was
stirred for additional 20 min, then moved into a freezer
and left for 1 h at -12 °C. The precipitated diethylenetri-
amine∙HCl was vacuum-filtered, and ether was evapo-
rated under vacuum. The product was transferred into a
100 mL round-bottom flask containing boiling stones and
a stirbar, and the unreacted diethylenetriamine was re-
moved by distillation (b.p. 50 - 60 °C, p = 0.01 torr, bath at
70 – 80 °C). Then the distillation apparatus was fitted
with a cow-type receiver and the bath temperature was
increased first to 140 °C, then to 160 °C. A small forerun
was collected, then the rest, until the source flask was dry.
The product distilled as a clear colorless, slightly viscous
liquid (b.p. 115 °C, p = 0.01 torr). Yield: 11.65 g (85%). The
product was 97-98% pure by 31P NMR, with several trace
impurities observable. 1H NMR (CD2Cl2): δ 3.01 (ddt, J=8.4,
6.4, 6, 2H, CH2), 2.70 (m, 2H, CH2), 2.64 (t, 3J=6, 2H, CH2),
2.59 (m, 2H, CH2), 1.49 (br. m, 1H, NH), 1.09 (s, 3H, NH),
1
impurity in the starting material). H NMR (benzene-d6):
δ 8.20 (d, J=8.8, 1H, CH), 7.56 (d, J=8.4, 1H, CH), 7.39 (d,
J=8.0, 1H, CH), 7.34 (m, 1H, CH), 7.13 (overlapped m, 2H,
CH), 3.96 (s, 2H, CH2), 3.03 (ddt, J=8.0, 6.0, 5.8, 2H, CH2),
2.62 (t, J=6.0, 2H, CH2), 1.95 (s, 1H, NH), 1.43 (m, 1H, NH),
1.03 (d, J=11.2, 18H, CH3). 13C{1H} NMR (benzene-d6) δ
161.75 (s), 148.89 (s), 136.30 (s), 130.12 (s), 129.74 (s), 128.10
(s), 127.99 (s), 126.32 (s), 121.02 (s), 56.44 (s, CH2), 52.82 (d,
J=7.1, CH2), 50.98 (d, J=28.7, CH2), 34.44 (d, J=21.3, C),
28.90 (d, J=15.1, CH3). 31P NMR (benzene-d6): δ 78.1.
MeO(CH2)2NH(CH2)2NHPtBu2 (ONP).
A
250-mL
round-bottom flask equipped with a stir bar was charged
with N-(2-methoxyethyl)ethane-1,2-diamine (ONN) (11.21
g, 94.9 mmol), triethylamine (11.5 g, 113.6 mmol), and THF
(100 mL). Then tBu2PCl (17.2 g, 95.2 mmol) was added
with stirring, and the mixture was left rapidly stirring for
24 h. The precipitated Et3N∙HCl was vacuum-filtered and
washed with 2 × 10 ml THF. The filtered solution was
evaporated under vacuum, and the product was isolated
by distillation. A forerun was collected (68 – 74 °C, 4.47 g,
18%), then the main fraction (74 - 94 °C, p < 0.01 torr,
18.25 g (73%)) as a clear colorless, slightly viscous liquid.
The forerun was 94% pure, by 31P NMR; the main product
3
1.04 (d, J(H,P)=11.2, 18H, CH3). 13C{1H} NMR (CD2Cl2): δ
53.16 (s, CH2), 52.66 (d, J(C,P)=6.8, CH2), 50.70 (d,
J(C,P)=27.9, CH2), 42.61 (s, CH2), 34.34 (d, J(C,P)=20.1, C),
28.61 (d, J(C,P)=14.9, CH3). 31P{1H} NMR (CD2Cl2) δ 78.6
(s).
Me2N(CH2)2NH(CH2)2NHPtBu2 (Me2NNP). A 250-mL
round-bottom flask equipped with a stir bar was charged
1
was spectroscopically pure. H NMR (benzene-d6): δ 3.29
(t, J=5.4, 2H, OCH2), 3.10 (s, 3H, OCH3), 3.03 (ddt, J=8.0,
6.0, 5.8, 2H, CH2), 2.66 (t, J=5.4, 2H, CH2), 2.59 (t, J = 5.8,
2H, CH2), 1.60 (br, 1H, NH), 1.52 (br. m, 1H, NH), 1.09 (d,
J=10.8, 18H, CH3). 13C{1H} NMR (benzene-d6) δ 72.84 (s,
OCH2), 58.83 (s, OCH3), 52.84 (d, J=7.1, CH2), 50.81 (d,
J=28.9, CH2), 49.87 (s, CH2), 34.42 (d, J=21.5, C), 28.88 (d,
J=15.3, CH3). 31P{1H} NMR (benzene-d6): δ 77.9 (s).
with
N-(2-(dimethylamino)ethyl)ethylendiamine
(Me2NNN) (10 g, 76.2 mmol), triethylamine (9.3 g, 91.9
mmol), and THF (50 mL). Then tBu2PCl (13.77 g, 76.2
mmol) was added with stirring, and the mixture was left
stirring rapidly over a weekend (the reaction most likely
finished within 24 h). The precipitated Et3N∙HCl was vac-
uum-filtered and washed with 2 × 10 ml THF. The filtered
solution was evaporated under vacuum, and the product
was isolated by distillation. A forerun was collected (25 –
36 °C, 0.79 g), followed by the main fraction (92 - 114 °C, p
= 0.01 torr, bath at 130 °C). Yield: 17.32 g (82.5%) of a clear
colorless, slightly viscous liquid. The product was 97-98%
EtS(CH2)2NH(CH2)2NHPtBu2 (SNP) A 200-mL round-
bottom flask equipped with a stir bar was charged with N-
(2-(ethylthio)ethyl)ethane-1,2-diamine (SNN) (10.0 g, 67.4
mmol), triethylamine (8.2 g, 81.0 mmol), and THF (50
mL). Then tBu2PCl (12.2 g, 67.5 mmol) was added with
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pure by 31P NMR, with several trace impurities observable.
rubber septum and the dark reaction mixture gradually
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1H NMR (benzene-d6): δ 3.07 (dq, J=8.3, 6.0, 2H, CH2N),
2.62 (t, J=5.8, 2H, NCH2), 2.58 (t, J=5.9, 2H, NCH2), 2.30 (t,
J=5.9, 2H, NCH2), 2.06 (s, 6H, CH2), 1.53 (br dt, J=12.2, 6.0,
1H, NH), 1.45 (br s, 1H, NH), 1.09 (d, J=11.2, 18H, CH3).
13C{1H} NMR (benzene-d6) δ 59.97 (s, CH2), 53.09, (d,
J=7.0, CH2), 50.94 (d, J=21.4, CH2), 48.02 (s, CH2), 45.91 (s,
NCH3), 34.40 (d, J=21.4, C), 28.88 (d, J=15.3, CH3).
turned light orange. Heating and stirring continued for 5
h. After cooling to r.t. in a cold water bath, the product
was filtered in air, washed with 4 × 30 mL of denatured
ethanol, and dried under vacuum until a constant weight.
Yield: 11.11 g (89%) of an off-white solid that was stored
and used in an Ar glovebox. A small amount (5-6 mol%)
of 2-ethoxyethanol remains in the product even after pro-
1
9
longed drying. H NMR (CD2Cl2): δ 7.33 (overlapped m,
c-C4H8N(CH2)2NH(CH2)2NHPtBu2 (PyrNP). A 250-mL
round-bottom flask equipped with a stir bar was charged
with N-(2-(pyrrolidin-1-yl)ethyl)ethylenediamine (PyrNN)
(10 g, 63.59 mmol), triethylamine (7.8 g, 77.08 mmol), and
THF (50 mL). Then tBu2PCl (11.5 g, 63.66 mmol) was add-
ed with stirring, and the mixture was left stirring rapidly
over a weekend (the reaction was most likely finished
within 24 h). The precipitated Et3N∙HCl was vacuum-
filtered and washed with 2 × 10 ml THF. The filtered solu-
tion was evaporated under vacuum. The semi-solid pro-
duced was dissolved in 40 mL of hexane and filtered; the
solids were washed with 2 × 20 mL of hexane. The hexane
was evaporated and the product was dried under vacuum
at 70 °C for 1 h. Yield: 16.88 g (88%) of a viscous colorless
liquid. The product was ca. 98% pure according to 31P
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Ph), 7.27 (t, J=7.6, Ph), 7.17 (overlapped m, Ph), 7.05 (t,
J=7.6, Ph), −8.66 (s, RuH).
RuHCl(CO)[κ3-PiNH(CH2)2NHPtBu2] (2). Anhydrous
ethanol (40 mL) was poured into a 100 mL flask equipped
with a magnetic stir bar and containing [RuCl2(COD)]n
(2.43 g, 8.67 mmol Ru), PiNP-tBu (2.56 g, 8.67 mmol), and
lithium (60.5 mg, 8.72 mmol). Stirring the resulting mix-
ture for 50 min gave a dark brown solution that was fil-
tered through a layer of Celpure P300 filter aid (1 g) in a
30 mL fritted funnel, and the filter material was washed
with 18 mL of anhydrous ethanol. The filtered solution
was transferred into a 300 mL steel autoclave equipped
with a magnetic stir bar, and more ethanol was used to
rinse the glassware, to bring the total solvent volume to
60 mL. The autoclave was closed, tightened, and placed
into an oil bath preheated to 170 °C on a hotplate stirrer.
This temperature was maintained for 3.5 h, while stirring
at 600 rpm. During this time, the pressure increased to
ca. 10 bar. Then, the autoclave was removed from and left
over the oil bath overnight. Next morning, the autoclave
was vented (slight positive pressure), opened in air, and
the crystalline product was isolated by vacuum filtration.
The autoclave and the filtered solid were liberally washed
with ca. 100 mL of denatured ethanol (in air), and the
product was dried under vacuum of an oil pump (0.01
mmHg) for 1 h (prolonged drying was found to have no
effect). Yield: 3.30 g (82.5%) of a crystalline orange solid.
1H NMR (CD2Cl2): δ 8.95 (m, 1H, Py), 7.71 (td, J=7.7, 1.5, 1H,
Py), 7.30 (m, 2H, Py), 4.25 (dd, J=14.0, 3.0, 1H, CH2), 4.03
(dd, J=25.1, 11.4, 1H, CH2), 3.93 (br, 1H, NH), 3.36 – 3.20 (m,
3H), 2.67 (m, 1H, CH2), 1.95 (br, 1H, NH), 1.39 (d, J=13.3,
9H, CH3), 1.28 (d, J=13.1, 9H, CH3), −15.10 (d, J=26.4, 1H).
13C{1H} NMR (CD2Cl2): δ 207.70 (d, J=18.1, CO), 157.33 (s,
Py), 153.28 (d, J=1.5, Py), 136.96 (s, Py), 124.58 (d, J=2.0,
Py), 121.22 (d, J=2.1, Py), 61.67 (d, J=2.1, CH2), 56.31 (d, J=1.2,
CH2), 45.36 (d, J=5.0, CH2), 42.36 (d, J=15.6, C), 38.48 (d,
J=33.6, C), 29.88 (d, J=5.2, CH3), 29.64 (d, J=4.2, CH3).
1
NMR. H NMR (benzene-d6): δ 3.09 (dq, J=8.4, 6.0, 2H,
CH2N), 2.68, 2.65 (overlapped, 4H, 2 × CH2), 2.55 (t, J=6.0,
CH2, NCH2), 2.36 (m, 4H, NCH2), 1.67 (br. s, 1H, NH), 1.60
(m, 4H, NCH2), 1.54 (br, 1H, NH), 1.09 (d, J=11.2, 18H, CH3).
13C{1H} NMR (benzene-d6) δ 56.66 (s, CH2), 54.63 (s, 2 ×
CH2), 53.13 (d, J=6.8, CH2), 50.92 (d, J=28.8, CH2), 49.23 (s,
CH2), 34.40 (d, J=21.5, C), 28.90 (d, J=15.3, CH3), 24.27 (s, 2
× CH2). 31P{1H} NMR (benzene-d6): δ 76.1 (s).
RuHCl(CO)(AsPh3)3. This is a modified procedure
based on the reported approach.19a,b Among the principal
changes are replacements of 2-methoxyethanol (a prohib-
ited substance in Canada) by 2-ethoxyethanol and of
aqueous formaldehyde by paraform. We further note that
the procedure reported in ref. 18a affords the product
containing ca. 5% of a non-hydride complex exhibiting
1
the characteristic H resonances at 7.77 – 7.79 and 7.43 –
7.48 ppm, outside the region (7.03 – 7.35 ppm) where the
phenyl protons of RuHCl(CO)(AsPh3) are observed in
CD2Cl2. Another procedure, reported in ref. 19c, where no
base was used, possibly yielded the yellow
RuCl2(CO)(AsPh3)3 described in ref 19b.
A 500 mL two-neck round-bottom flask equipped with
a stirbar and having one neck closed by a rubber septum
was loaded in air with RuCl3∙nH2O (3 g, ca. 11.47 mmol),
AsPh3 (17 g, 55.51 mmol), and paraformaldehyde (6 g, 0.2
mol); then 150 mL of 2-ethoxyethanol (ReagentPlus®, 99%)
was added. The flask was fitted with a reflux condenser
which upper joint was connected with a vacuum/Ar line;
then the flask was placed into an oil bath, on top of a hot-
plate stirrer. With rapid stirring established, the flask was
opened to vacuum for 2-3 seconds and refilled with argon;
this procedure was repeated six times. Heating was
turned on, with the bath temperature set to 135 °C. In 20
min (after heating the mixture for 7 - 10 min at 132 – 135
°C), NEtiPr2 (4 g, 30.95 mmol) was syringed in through the
31P{1H} NMR (CD2Cl2)
δ 125.8 (s). Anal. Calcd for
C17H31ClN3OPRu: C, 44.30; H, 6.78; N, 9.12. Found: C,
44.43; H, 6.81; N, 9.03.
RuHCl(CO)[κ3-PiNH(CH2)2NHP(o-Tol)2]
(3).
RuHCl(CO)(AsPh3)3 (3.71 g, 3.42 mmol) and PiNP-oTol
(1.3 g, ca. 3.59 mmol) in 20 mL of diglyme were loaded
into a 75 ml pressure bottle (heavy-wall round bottom
single-neck flask with a PTFE bushing as a seal). The ves-
sel was sealed and placed in a preheated to 162 °C oil bath
and stirred for 2 h, affording a brown solution. This solu-
tion was filtered through a layer of Celpure P300 filter aid
(1 g) in a 30 mL fritted funnel, and the filter material was
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washed with 3 mL of diglyme. Addition of 43 mL of Et2O
equipped with a magnetic stir bar and containing
[RuCl2(COD)]n (2.2 g, 7.85 mmol Ru), QuiNP (3 g, ca. 7.85
mmol), and lithium (54.5 mg, 7.85 mmol). Stirring this
mixture for 1 h gave a dark solution that was transferred
into a 300 mL steel autoclave equipped with a magnetic
stir bar, and more ethanol was used to rinse the glass-
ware, to bring the total solvent volume to 60 mL. The
autoclave was closed, tightened, and placed into an oil
bath preheated to 170 °C on a hotplate stirrer. This tem-
perature was maintained for 4 h, while stirring at 600
rpm, then the system was left at r.t. overnight. The prod-
uct was isolated by filtration, washed with 3 × 10 mL of
ethanol, and dried under vacuum of an oil pump (0.01
mmHg) for 3 h. Yield: 2.72 g (68%) of a light-orange crys-
talline solid of 5 with ca 12.5 mol% of co-crystallized etha-
nol. 1H NMR (CD2Cl2): δ 9.35 (d, J=8.7, 1H), 8.18 (d, J=8.4,
1H), 7.88 (m, 2H), 7.62 (m, 1H), 7.34 (d, J=8.4, 1H), 4.47
(dd, J=15.2, 3.3, 1H, CH2), 4.37 (dd, J=15.2, 12.4, 1H, CH2),
4.24 (br m, 1H, NH), 3.37 (overlapped m, 3H, CH2), 2.73 (q,
J=10.0, 1H, CH2), 1.96 (br m, 1H, NH), 1.47 (d, J=13.4, 9H,
CH3), 1.28 (d, J=13.1, 9H, CH3), −15.79 (d, J=27.6, 1H, RuH).
13C{1H} NMR (CD2Cl2): δ 207.57 (d, J=20.3, CO), 159.80 (s),
148.15 (s), 138.12 (s), 131.94 (s), 131.06 (s), 128.95 (d, J=1.7),
128.41 (s), 127.67 (s), 118.15 (d, J=2.1), 63.59 (d, J=1.5, CH2),
55.61 (d, J=1.3, CH2), 44.62 (d, J=5.2, CH2), 42.67 (d, J=18.9,
C), 39.29 (d, J=33.8, C), 30.24 (d, J=4.8, CH3), 29.60 (d,
resulted in precipitation of beige solid which was filtered,
washed with 4 × 7 mL of Et2O and dried under vacuum
for 3 h. Yield: 1.13 g (62%). This crude product was further
purified by recrystallization from 20 mL of ethanol heated
1
to reflux. H NMR (CD2Cl2): δ 8.96 (dd, J=3.3, 2.1, 1H, Py),
8.55 (m, 1H, Py), 7.75 (overlapped m, 2H), 7.22 (over-
lapped m, 8H), 4.33 (m, 1H, CH2), 4.12 (overlapped, 2H,
NH+CH2), 3.46 (overlapped m, 2H, CH2), 3.32 (m, 1H,
CH2), 2.94 (m, 1H, CH2), 2.61 (br m, 1H, NH), 2.26 (s, 3H,
CH3), 2.13 (s, 3H, CH3), −14.44 (d, J=28.5, 1H, RuH). 13C
NMR (CD2Cl2): δ 206.51 (d, J=19.3, CO), 157.39 (s), 153.38
(d, J=1.5), 139.55 (d, J=2.5), 139.50 (s), 138.73 (d, J=39.0),
137.25 (s), 137.20 (d, J=22.5), 134.17 (s), 132.83 (d, J=17.1),
132.38 (d, J=7.9), 131.54 (d, J=6.4), 130.25 (d, J=2.3), 130.04
(d, J=2.3), 129.17 (s), 125.95 (d, J=11.9), 125.71 (d, J=13.3),
124.55 (d, J=2.2), 121.44 (d, J=2.3), 61.63 (d, J=2.0, CH2),
55.85 (d, J=1.2, CH2), 44.27 (d, J=8.4, CH2), 22.58 (d, J=3.8,
CH3), 22.34 (d, J=3.9, CH3). 31P{1H} NMR (CD2Cl2): δ 99.5
(s). Anal. Calcd for C23H27ClN3ORuP: C, 52.22; H, 5.14; N,
7.94. Found: C, 52.23; H, 5.10; N, 7.91.
9
10
11
12
13
14
15
16
17
18
19
20
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22
23
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RuHCl(CO)[κ3-PiCH2NH(CH2)2NHPtBu2]∙EtOH (4).
Anhydrous ethanol (40 mL) was poured into a 100 mL
flask equipped with a magnetic stir bar and containing
[RuCl2(COD)]n (2.35 g, 8.39 mmol Ru), PiCH2NP-tBu (2.6
g, 8.40 mmol), and lithium (58.6 mg, 8.44 mmol). Stirring
this mixture for 40 min gave a dark solution that was
transferred into a 300 mL steel autoclave equipped with a
magnetic stir bar, and more ethanol was used to rinse the
glassware, to bring the total solvent volume to 60 mL. The
autoclave was closed, tightened, and placed into an oil
bath preheated to 170 °C on a hotplate stirrer. This tem-
perature was maintained for 4 h, while stirring at 600
rpm. After cooling to r.t., the autoclave was vented and
opened under argon. The dark-yellow product solution
was filtered through a layer of Celpure P300 filter aid. The
product crystallized in 1 h, upon evaporation of ca 50% of
the solvent under vacuum of an oil pump. The solid was
filtered, washed with 3 × 10 mL of ethanol, and dried un-
der vacuum of an oil pump (0.01 mmHg) for 1 h. Yield:
31
J=3.8, CH3). P{1H} NMR (CD2Cl2): δ 127.4 (s). Anal. Calcd
for C21H33ClN3ORuP∙0.125EtOH: C, 49.38; H, 6.59; N, 8.12.
Found: C, 49.40; H, 6.57; N, 8.12.
RuHCl(CO)[κ3-MeO(CH2)2NH(CH2)2NHPtBu2]
(6).
[RuCl2(COD)]n (1.31 g, 4.68 mmol Ru), ONP (1.23 g, ca.
4.69 mmol), and lithium (32.7 mg, 4.71 mmol) were
stirred in 20 mL of anhydrous methanol in a 50 mL flask
for 2 h. The product mixture was transferred into a 300
mL steel autoclave equipped with a magnetic stir bar, and
more methanol was used to rinse the glassware, to bring
the total solvent volume to 30 mL. The autoclave was
closed, tightened, and placed into an oil bath preheated
to 170 °C on a hotplate stirrer. This temperature was
maintained for 3.5 h, while stirring at 600 rpm, then the
system was left at r.t. overnight. The product was isolated
by filtration, washed with 3 × 10 mL of methanol, and
dried under vacuum of an oil pump (0.01 mmHg) for 3 h.
Yield: 0.65 g (32%) of a large-crystalline yellow solid of 6.
1H NMR (CD2Cl2): δ 3.73 (s, 3H, OCH3), 3.72 (td, J=10.6,
3.4, 1H, OCH2), 3.63 (br, 1H, NH), 3.34 (overlapped m, 2H,
OCH2 + NCH2), 3.19 (m, 2H, NCH2), 2.84 (m, 2H, NCH2),
2.64 (m, 1H, NCH2), 1.91 (br m, 1H, NH), 1.33 (d, J=13.5, 9H,
CH3), 1.19 (d, J=13.4, 9H, CH3), −16.19 (d, J=30.3, 1H, RuH).
13C{1H} NMR (CD2Cl2): δ 206.87 (d, J=21.4, CO), 70.72 (s,
OCH2), 63.43 (s, OCH3), 57.60 (d, J=1.1, CH2), 53.60 (s,
CH2), 46.00 (d, J=2.4, CH2), 42.85 (d, J=19.1, C), 38.85 (d,
J=38.8, C), 29.87 (d, J=3.5, CH3), 29.41 (d, J=4.8, CH3).
31P{1H} NMR (CD2Cl2): δ 139.5 (s). Anal. Calcd for
C14H32ClN2O2RuP: C, 39.30; H, 7.54; N, 6.55. Found: C,
39.09; H, 7.68; N, 6.32.
1
2.59 g (59%) of a pale-yellow solid of 4∙EtOH. H NMR
(CD2Cl2): δ 9.25 (m, 1H), 7.69 (td, J = 7.6, 1.7, 1H), 7.25 (m,
2H), 3.80 (m, 2H), 3.63 (qd, J=7.0, 5.3, 2H, EtOH), 3.6 (br
s, 1H, NH), 3.14 (m, 2H), 2.99 (m, 1H), 2.91 (m, 1H), 2.60
(m, 2H), 1.96 (br m, 1H, NH), 1.51 (t, J=5.3, 1H, OH), 1.37 (d,
J = 13.2, 9H, CH3), 1.31 (d, J=12.9, 9H, CH3), 1.18 (t, J=7.0,
3H, EtOH), −15.37 (d, J=28.1, 1H, RuH). 13C{1H} NMR
(CD2Cl2): δ 206.81 (d, J=19.4, CO), 161.38 (d, J=0.5, Py),
157.17 (d, J=1.7, Py), 137.53 (s, Py), 124.51 (d, J=2.6, Py),
122.72 (d, J=1.7, Py), 58.60 (s, CH2, ethanol), 57.41 (d, J=2.4,
CH2), 49.58 (s, CH2), 43.77 (d, J=5.4, CH2), 41.34 (d, J=20.6,
C), 39.80 (s, CH2), 39.44 (d, J=31.6, C), 30.15 (d, J=4.9,
CH3), 29.34 (d, J=4.1, CH3), 18.83 (s, CH3). 31P{1H} NMR
(CD2Cl2):
δ
124.6
(s).
Anal.
Calcd
for
C18H33ClN3ORuP∙EtOH: C, 46.10; H, 7.54; N, 8.06. Found:
C, 46.00; H, 7.58; N, 8.03.
RuHCl(CO)[κ3-QuiCH2NH(CH2)2NHPtBu2] (5). An-
hydrous ethanol (50 mL) was poured into a 100 mL flask
RuHCl(CO)[κ3-EtS(CH2)2NH(CH2)2NHPtBu2]
(7).
[RuCl2(COD)]n (2.5 g, 8.92 mmol Ru), SNP (2.65 g, 9.06
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1
mmol), and lithium (62.2 mg, 8.96 mmol) were stirred in
and more ethanol was used to rinse the glassware, to
2
3
4
5
6
7
8
9
21 mL of anhydrous ethanol in a 50 mL flask for 2 h. The
product solution was filtered through a layer of Celpure
P300 filter aid (1 g) in a 30 mL fritted funnel, and the filter
material was washed with 17 mL of ethanol. The filtrate
was transferred into a 300 mL steel autoclave equipped
with a magnetic stir bar, and 2 mL of ethanol was used to
rinse the glassware, to bring the total solvent volume to
40 mL. The autoclave was closed, tightened, and placed
into an oil bath preheated to 170 °C on a hotplate stirrer.
This temperature was maintained for 3.5 h, while stirring
at 600 rpm, then the system was left at r.t. overnight. The
product was isolated by filtration, washed with 3 × 10 mL
of ethanol, and dried under vacuum of an oil pump (0.01
mmHg) for 3 h. Yield: 2.68 g (65%) of an off-white solid of
7. In solution, 7 exist as a 3:1 mixture of two isomers with
the Et group on the opposite sides of the SNP ligand
plane. 1H NMR (CD2Cl2): δ 3 – 3.4 (overlapped m, 6H), 2.4
– 2.8 (overlapped m, 5H), 2.06 (br m, 1H, NH), 1.39 (d,
J=13.2, 9H, CH3), 1.37 (t, J=7.4, 3H, CH3), 1.26 (d, J=13.2, 9H,
CH3), −16.31 (d, J=25.2, RuH, major isomer), −16.44 (d,
bring the total solvent volume to 60 mL. The autoclave
was closed, tightened, and placed into an oil bath pre-
heated to 170 °C on a hotplate stirrer. This temperature
was maintained for 3.5 h, while stirring at 600 rpm; then
the system was left at r.t. overnight. The product was iso-
lated by filtration, washed with 3 × 10 mL of ethanol, and
dried under vacuum of an oil pump (0.01 mmHg) for 3 h.
This yielded 1.68 g of a light-yellow crystalline solid. A
second crop (0.68 g) was obtained from the mother liquor
left in a freezer at −18 °C. Total yield: 2.36 g (59%). Com-
plex 9 crystallized with ca. 31 mol% of cyclooctene (based
on the 1H and 13C NMR data). 1H NMR (CD2Cl2): δ 3.54 (br
m, 1H, NH), 3.30 (m, 1H, CH2), 3.18 (m, 1H, CH2), 3.02 (m,
3H, CH2), 2.93 (d, J=1.6, 3H, CH3), 2.81 (s, 3H, CH3), 2.77
(dtd, J=13.8, 12.2, 3.1, 1H, CH2), 2.58 (tdd, J = 11.6, 9.9, 1.7
Hz, 1H), 2.01 (dt, J = 12.4, 3.1 Hz, 1H, CH2), 1.93 (br m, 1H,
NH), 1.33 (d, J=13.1, 9H, CH3), 1.21 (d, J=13.0, 9H), −16.18 (d,
J=28.3, 1H, RuH). 13C{1H} NMR (CD2Cl2): δ 208.32 (d, J =
18.8, CO), 59.54 (d, J=1.2, CH2), 57.59 (d, J=1.7, CH3), 57.06
(d, J= 1.2, CH2), 53.19 (d, J=1.8, CH3), 52.20 (d, J=1.9, CH2),
46.13 (d, J=3.7, CH2), 42.71 (d, J=12.6, C), 38.24 (d, J=36.4,
C), 29.78 (d, J=3.8, CH3), 29.61 (d, J=5.3, CH3). 31P{1H} NMR
10
11
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45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
J=24.4, RuH, minor isomer). C{1H} NMR (major isomer,
CD2Cl2): δ 206.51 (d, J=19.3, CO), 57.47 (d, J=1.2, CH2),
54.50 (d, J=2.5, CH2), 46.35 (d, J=4.53, CH2), 43.41 (d,
J=12.6, C), 38.30 (d, J=34.5, C), 36.50 (s, SCH2), 31.47 (d,
J=0.9, SCH2), 29.73, (overlapped d, CH3), 13.47 (s, CH3).
31P{1H} NMR (CD2Cl2): δ 117.5 (s, major isomer, 76%), 117.8
(s, minor isomer, 24%). Anal. Calcd for C15H34ClN2OPRuS:
C, 39.34; H, 7.48; N, 6.12; S, 7.00. Found: C, 39.42; H, 7.53;
N, 6.06; S, 6.82.
(CD2Cl2):
δ
126.4
(s).
Anal.
Calcd
for
C15H35ClN3OPRu∙0.315C8H14: C, 44.24; H, 8.35; N, 8.83.
Found: C, 44.08; H, 8.70; N, 8.80.
RuHCl(CO)[κ3-c-C4H8N(CH2)2NH(CH2)2NHPtBu2]
(10). [RuCl2(COD)]n (2.4 g, 8.57 mmol Ru), PyrNP (2.68 g,
8.89 mmol), and lithium (60.3 mg, 8.69 mmol) were
stirred in 40 mL of anhydrous ethanol in a 100 mL flask
for 1 h. The reaction mixture was transferred into a 300
mL steel autoclave equipped with a magnetic stir bar, and
more ethanol was used to rinse the glassware, to bring the
total solvent volume to 60 mL. The autoclave was closed,
tightened, and placed into an oil bath preheated to 170 °C
on a hotplate stirrer. This temperature was maintained for
3.5 h, while stirring at 500 rpm; then the system was left
at r.t. overnight. The product was isolated by filtration,
washed with 3 × 10 mL of ethanol, and dried under vacu-
um of an oil pump (0.01 mmHg) for 1 h. This yielded 2.73
g of a light-yellow crystalline solid. A second crop (0.23 g)
was obtained from the mother liquor left in a freezer at
−18 °C. Total yield: 2.96 g (74%). Complex 10 crystallized
RuHCl(CO)(κ3-H2NNP-tBu) (8). RuHCl(CO)(AsPh3)3
(2.63 g, 2.43 mmol) and H2N(CH2)2NH(CH2)2NHPtBu2
(0.6 g, 2.43 mmol) in 10 mL of diglyme were loaded into a
pressure bottle (heavy-wall round bottom single-neck
flask with a PTFE bushing as a seal). The vessel was sealed
and placed in a preheated to 160 °C oil bath and stirred
for 2 h, affording a white suspension. The flask was placed
in a cold water bath for 30 min, and the precipitate was
filtered off, washed with diglyme (4 × 3 mL), and dried
under vacuum for 3 h to give a pale-yellow solid. Yield:
876 mg (87.5%). 1H NMR (CD2Cl2): δ 3.43 (s, 1H, NH), 3.35
(m, 1H, CH2), 3.20 (m, 1H, CH2), 3.09 (overlapped m, 3H,
NH2+CH2), 2.91 (overlapped m, 3H, CH2), 2.61 (m, 1H,
CH2), 2.51 (qd, J=12.1, 5.8, 1H, CH2), 1.97 (br m, 1H, NH),
1.36 (d, J=13.1, 9H), 1.21 (d, J=13.0 Hz, 9H, CH3), −16.40 (d,
J=26.1, 1H, RuH). 13C{1H} NMR (CD2Cl2): δ 207.12 (d, J =
18.7, CO), 57.10 (d, J=1.0, CH2), 56.12 (d, J=2.9, CH2), 46.42
(d, J=4.0, CH2), 42.60 (d, J=14.3, C), 40.29 (d, J=1.1, CH2),
38.11 (d, J=34.9, C), 29.79 (d, J=4.0, CH3), 29.49 (d, J=5.4,
CH3). 31P{1H} NMR (CD2Cl2): δ 125.6 (s). Anal. Calcd for
C13H31ClN3OPRu: C, 37.82; H, 7.57; N, 10.18. Found: C,
37.70; H, 7.62; N, 10.10.
1
13
with ca. 18 mol% of cyclooctene (based on the H and C
1
NMR data). H NMR (CD2Cl2): δ 3.89 (m, 1H, CH2), 3.50
(m, 1H, CH2), 3.46 (br m, 1H, NH), 3.38-3.17 (overlapped
m, 2H, CH2), 3.19 (ddd, J=13.9, 12.6, 3.3, 1H, CH2), 3.03 (m,
2H, CH2), 2.87 (dddd, J=11.4, 8.8, 6.2, 2.6, 1H, CH2), 2.72
(overlapped m, 2H, CH2), 2.59 (tdd, J=11.5, 9.8, 1.7, 1H,
CH2), 2.11 (m, 3H, CH2), 1.94 (br m, 1H, NH), 1.84 (m, 2H,
CH2), 1.34 (d, J=13.1, 9H, CH3), 1.21 (d, J=12.9, 9H, CH3),
−16.25 (d, J=28.1, 1H, RuH). 13C{1H} NMR (CD2Cl2): δ 208.40
(d, J=19.5, CO), 66.08 (d, J=1.3, CH2), 60.77 (d, J=1.6, CH2),
57.05 (d, J=0.8, CH2), 56.98 (d, J=1.3, CH2), 46.20 (d, J=3.5,
CH2), 42.93 (d, J=13.1, C), 38.40 (d, J=36.2, C), 29.95 (d,
J=3.8, CH3), 29.53 (d, J=5.3, CH3), 23.57 (d, J=0.4, CH2),
22.66 (s, CH2). 31P{1H} NMR (CD2Cl2): δ 125.6 (s). Anal.
RuHCl(CO)[κ3-Me2N(CH2)2NH(CH2)2NHPtBu2] (9).
[RuCl2(COD)]n (2.54 g, 9.07 mmol Ru), Me2NNP (2.6 g,
9.44 mmol), and lithium (62.9 mg, 9.06 mmol) were
stirred in 40 mL of anhydrous ethanol in a 100 mL flask
for 40 min. The reaction solution was transferred into a
300 mL steel autoclave equipped with a magnetic stir bar,
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1
2
3
4
5
6
7
Calcd for C17H37ClN3OPRu∙0.18C8H14: C, 45.49; H, 8.18; N,
8.63. Found: C, 45.23; H, 8.54; N, 8.59.
heated tubes were removed from the bath first after 30
min, second after 60 min of heating, and the NMR spectra
were recorded at room temperature. Analogous experi-
ments were conducted using normal (12C) ethyl acetate
and reproduced the turnover numbers reported in this
paper.
Details of the catalytic studies. All reaction solutions
1
13
were analyzed with the help of H and C{1H} NMR spec-
troscopy. The proton spectra were collected using a 30 sec
relaxation (pre-acquisition) delay for accurate integration.
Computational details. The calculations were carried
out in Gaussian 0920 using the M06-L functional21a and the
ultrafine integration grid (a pruned (99,590) grid). Struc-
tures TS5, TS6, 30, and 31 were also optimized at the
ωB97X-D level.21b The basis sets, listed by their G09 key-
words, included QZVP22a,b (with def2 ECP) for Ru and Os,
together with the W06 density fitting basis set in the
M06-L calculations. For the non-metal atoms of 2 – 12 we
employed TZVP22c,d together with the TZVP density fitting
basis set. The free energies of all species in Schemes 5 – 11
were calculated using def2TZVP for the non-metal atoms
(together with the W06 density fitting basis set at the
M06-L level). The polarizable continuum model
(IEFPCM) was used in all calculations of Schemes 5 – 10 in
ethanol solvent, with the radii and non-electrostatic
terms of Truhlar and co-workers’ SMD solvation model
(scrf=smd).23 All geometry optimizations without excep-
tion (i.e., no single points) were accompanied by frequen-
cy calculations, which also provided the enthalpies and
free energies at 298.15 K, under pressure = 419 atm for
ethanol solvent, following the approach of Martin and co-
workers.24 Representative examples of the input files are
provided in the Supporting information.
Hydrogenation. The hydrogenation experiments of
Scheme 4 (eq 3) were performed under initial p(H2) = 50
bar using 20 mmol of methyl undecenoate in 7 mL of
THF. All chemicals were loaded in a 75 mL stainless-steel
Parr reactor inside of an argon glovebox. The pressurized
reactor (disconnected from the hydrogen tank) was
placed into an oil bath preheated to 100 °C on a hotplate
stirrer. This temperature was maintained for 2.5 h while
stirring at 500 rpm using a 1.3×0.95 cm rare-earth samari-
um-cobalt spinbar.
8
9
10
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60
Acceptorless dehydrogenative coupling experiments of
Scheme 1 (eq 1 and 2). In an argon glovebox, the required
amounts of the catalysts and NaOEt were weighted into
two 50 mL Schlenk tubes (also containing micro stirbars)
on a calibrated analytical balance accurate to 0.1 mg.
Next, the required amounts of the substrates (total vol-
ume: 10 - 12 mL) were weighted into these tubes on a bal-
ance accurate to 1 mg. After taking the tubes out of the
box, they were connected to a vacuum/Ar manifold. Un-
der argon, the stoppers were replaced by finger conden-
sers connected to a circulating refrigerated bath. When
the temperature in the bath reached −5 °C, the flasks were
placed in an ethylene glycol bath, the argon tank was
closed, and H2 produced as the bath temperature in-
creased to 90 °C was allowed to pass freely through a
mineral oil bubbler (independently from each reaction
flask). Throughout the reaction, the temperature in the
cold fingers was maintained between −10 and −15 °C and
in the bath at 90 °C while stirring at 1100 rpm. This exper-
imental setup can be seen pictured in Figure S2 of ref. 7.
ASSOCIATED CONTENT
Supporting Information. NMR spectra of the reactions
between EtOH, BuNH2, and 1-13C ethyl acetate with and
without 22, and all computational details are supplied as
Supporting Information. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Details of the NMR tube studies.
The Tishchenko reaction: In an argon glovebox, 5.0 mg
of 22∙0.25THF (9.4 μmol) was weighted into an NMR tube
on a calibrated analytical balance accurate to 0.1 mg.
Next, 1.43 g of benzene-d6 followed by 0.41 g of acetalde-
hyde (9.4 mmol, S/C = 1,000) (total volume ca. 2 mL, ca.
4.7 M acetaldehyde) were weighted into the NMR tube on
a balance accurate to 1 mg. The tube was capped, vigor-
ously shaken, and removed from the box for immediate
collection of the NMR spectra.
Experiments with 1-13C-ethyl acetate: In an argon glove-
box, two NMR tubes were loaded with 2.7 mg each of
22∙0.25THF (5.06 μmol) on a calibrated analytical balance
accurate to 0.1 mg. Next, a mixture of ethanol (0.70 g, 15.2
mmol), butylamine (1.11 g, 15.2 mmol) and 1-13C-ethyl ace-
tate (68 mg, 0.76 mmol) was divided equally between
three NMR tubes, two of which contained 22. The tubes
were capped, vigorously shaken, and removed from the
box. Two of the tubes were placed in a bath pre-heated to
80 °C, whereas the third tube (containing 22) remained at
23 °C. No significant reaction was observed at 23 °C. The
Corresponding Author
*E-mail: dgoussev@wlu.ca.
Author Contributions
The manuscript was written through the sole contribution of
the author, who have given approval to the final version of
the manuscript.
ACKNOWLEDGMENT
Insightful discussions of Schemes 5, 8, and 11 with Prof. Faraj
Hasanayn are gratefully acknowledged. Financial support of
this work by Wilfrid Laurier University, CFI and NSERC of
Canada is greatly appreciated.
REFERENCES
(1) (a) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am.
Chem. Soc. 2005, 127, 10840-10841. (b) Zhang, J; Leitus, G.; Ben-
David, Y.; Milstein, D. Angew. Chem. Int. Ed. 2006, 45, 1113-1115.
(c) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317,
790-792; (d) Balaraman, E.; Gnanaprakasam, B.; Shimon, L. J. W.;
Milstein, D. J. Am. Chem.Soc. 2010, 132, 16756-16758.
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