Synthesis of oxalamides by acceptorless dehydrogenative coupling of ethylene glycol and amines and the reverse hydrogenation catalyzed by ruthenium

Article abstract of DOI:10.1039/d0sc02065f

A sustainable, new synthesis of oxalamides, by acceptorless dehydrogenative coupling of ethylene glycol with amines, generating H2, homogeneously catalyzed by a ruthenium pincer complex, is presented. The reverse hydrogenation reaction is also accomplished using the same catalyst. A plausible reaction mechanism is proposed based on stoichiometric reactions, NMR studies, X-ray crystallography as well as observation of plausible intermediates.

Full text of DOI:10.1039/d0sc02065f

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DOI: 10.1039/D0SC02065F
Journal Name
ARTICLE
Synthesis of oxalamides by acceptorless dehydrogenative cou-
pling of ethylene glycol and amines and the reverse hydrogena-
tion catalyzed by ruthenium
Received 00th January 20xx,
Accepted 00th January 20xx
You-Quan Zou,a,#,¶ Quan-Quan Zhou,a,# Yael Diskin-Posner,b Yehoshoa Ben-David,a and David
DOI: 10.1039/x0xx00000x
Milstein* a
www.rsc.org/
A sustainable, new synthesis of oxalamides, by acceptorless dehydrogenative coupling of ethylene glycol with amines,
generating H2, homogeneously catalyzed by a ruthenium pincer complex, is presented. The reverse hydrogenation reaction
is also accomplished using the same catalyst. A plausible reaction mechanism is proposed based on stoichiometric
reactions, NMR studies, X-ray crystallography as well as observation of plausible intermediates.
Figure 1. Representative examples of functional molecules
containing an oxalamide moiety.
Conventional methods for the synthesis of oxalamides are largely
Introduction
Oxalamide skeletons are prevalent in many biologically active
molecules and pharmaceuticals, such as Lixiana (1, Figure 1), widely
used as an anticoagulant.1 Oxalamide 2 shows promising antiviral
activity of entry inhibitors targeting the CD4-binding site of HIV-1.2
Additionally, oxalamides are employed as robust ligands in copper
catalyzed cross coupling reactions (e.g., compounds 3-5).3 Besides
these, oxalamides are also popular in food processing as flavoring
agents (oxalamide 6)4 and in drug delivery as a synthon of
organosilica nanoparticles (oxalamide 7)5. Given the importance of
oxalamides, there is considerable interest in the development of
novel, efficient protocols for their preparation.
based on the reaction of oxalic acid with thionyl chloride to form
oxalyl chloride followed by treatment with amines (Figure 2a).3,6
Other methods such as oxidative carbonylation of amines using
carbon monoxide7a-b and aminolysis of oxalates7c-d also lead to the
formation of oxalamides. However, these methods are either not
atom economic, generate stoichiometric amounts of waste, or
involve acrid or toxic agents. Therefore, the development of atom-
economic green and sustainable methods for the efficient
construction of oxalamides is highly desirable and remains an
important goal both in chemical and pharmaceutical industries.
(a) Synthesis of oxalamides from oxalic acid
O
O
O
O
N
O
N
O
O
O
O
N
OH
R
NH2
O
O
SOCl2
N
N
H
Cl
S
N
R
N
H
N
H
R
HO
OH
Cl
Cl
H
H
H
Cl
N
H
N
H
N
O
N
S
F
(b) Acceptorless dehydrogenative coupling of alcohols with amines
N
1
2
synthesis of amides:
O
O
O
O
O
Ru
R2
R2 NH2
R1
OH
H2
+
+
R1
O
N
H
N
H
N
H
N
H
N
H
X
X
synthesis of polyamides:
3
4
5
(X = O), (X = S)
O
n
HO
OH
O
O
Ru
O
O
N
H
N
H
+
n
N
N
H
N
H
n H2N
(EtO)3Si
N
H
N
H
Si(OEt)3
NH2
H2
+
This work
(c)
: synthesis of oxalamides and the reverse hydrogenation
6
7
 H2
O
O
R
NH2
2
+
Ru
N
R
N
H
N
H
R
aDepartment of Organic Chemistry and b Chemical Research Support, Weizmann
Institute of Science, Rehovot 76100, Israel
HO
OH
L1
Ru
L2
 H2
E-mail: david.milstein@weizmann.ac.il
#You-Quan Zou and Quan-Quan Zhou contributed equally.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See DOI:
10.1039/x0xx00000x
high efficiency
broad substrate scope
atom-economy
reversibility
Figure 2. (a) Conventional synthesis of oxalamides, (b)
dehydrogenative amide bond formation, and (c) this work
.
¶Present address: Department of Chemistry, University of Cambridge, Lensfield
Road, Cambridge, CB2 1EW, UK
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In 2007, we reported the ruthenium catalyzed dehydrogenative (entry 10). Accordingly, the optimal reaction condVitieiownAsrticfloerOntlhinee
DOI: 10.1039/D0SC02065F
coupling of alcohols with amines leading to the environmentally acceptorless dehydrogenative coupling are as depicted in entry 6: 1
benign synthesis of amides with H2 liberation as the sole byproduct mol% of Ru-5 as catalyst, 2 mol% of tBuOK as base, 135 oC in 2.0 mL
(Figure 2b).8 Guan’s group9a and our group9b also demonstrated the of toluene.
ruthenium pincer complex catalyzed dehydrogenative coupling of
diols and diamines, to form polyamides. Other Ru-catalyzed Table 1. Optimization of the reaction conditions
systems for the synthesis of amides from amines and alcohols were
O
N
O
N
HO
Ru
(1 mol%)
OH
subsequently reported.10 Recently, we,11a-d Prakash11e and Liu
groups11f have developed several liquid organic hydrogen carrier
systems based on amide bond formation and the reverse
hydrogenation reactions.
tBuOK (1-2 mol%)
H
H
+
Solvent, 135 C, 24 h
NH2
H
+
8a
9a
2
entrya
Ru
tBuOK
solvent
yield (%)b
Ethylene glycol (EG) is an inexpensive and convenient feedstock
in industry,12 which can be accessed from renewable biomass-
derived hydrocarbons.13 Very recently, we disclosed a reversible
liquid organic hydrogen carrier system based on EG, capable of
chemically loading and unloading hydrogen.14 In this system, EG
undergoes acceptorless dehydrogenative esterification to
oligoesters, and then the oligoesters are hydrogenated back to EG
by using a ruthenium pincer catalyst. As part of our ongoing
research program on green and sustainable homogeneous catalysis,
we herein report an atom-economic and environmentally benign
strategy for the direct synthesis of oxalamides via acceptorless
dehydrogenative coupling of EG with amines (Figure 2c). A potential
challenge is the coordination ability of oxalamides as chelating
ligands3, which could possibly result in product inhibition.
1
2
Ru-1
Ru-2
Ru-3
Ru-4
Ru-5
Ru-5
Ru-5
Ru-5
Ru-5
Ru-6
1 mol%
1 mol%
1 mol%
2 mol%
2 mol%
2 mol%
2 mol%
2 mol%
2 mol%
--
Toluene/DME
Toluene/DME
Toluene/DME
Toluene/DME
Toluene/DME
Toluene
26
50
40
37
77
86
71
84
81
27
3
4
5
6
7
DME
8
THF
We envisioned that dehydrogenative coupling of EG and the
amine will first form an α-hydroxy amide. Subsequently, the
resulting α-hydroxy amide would react with another molecule of
amine to form the desired oxalamide via a similar catalytic cycle. In
addition, the reverse hydrogenation of oxalamides back to EG and
amines was also investigated using the same catalyst. To the best of
our knowledge, there has hitherto been no report on acceptorless
dehydrogenative synthesis of oxalamides from EG and amines, the
only byproduct being hydrogen gas, valuable by itself.
9
1,4-Dioxane
Toluene
10
tBu
tBu
iPr
Cl
Cl
tBu
tBu
Cl
P
P
P
iPr
N
Ru CO
N
Ru CO
N
Ru CO
H
H
H
N
N
N
Et
Et
Ru-1
Ru-3
Ru-2
Cl
H
tBu
tBu
Cl
Results and discussion
H
P
P
tBu
tBu
iPr
N
To examine the feasibility of the acceptorless dehydrogenative
coupling of ethylene glycol and amines, our initial studies were
focused on the reaction of EG and hexan-1-amine (8a). At the
beginning, we tested the catalytic efficiency of ruthenium pincer
complex Ru-115 which upon deprotonation forms the dearomatized
complex and catalyzes the synthesis of amides and polyamides from
amines and alcohols.8 The reaction did indeed take place using Ru-1
P
N
Ru CO
N
Ru CO
iPr
iPr
iPr
Ru
H
H
tBu
H
N
N
P
H
H
Bn
CO
Ru-6
Ru-4
Ru-5
aReaction conditions: ethylene glycol (1.0 mmol), 8a (3.0 mmol), Ru
catalyst (1 mol%), tBuOK (1-2 mol%), and solvent (2.0 mL) at 135 oC
(bath temperature) for 24 hours in a closed system. bIsolated yield.
DME: dimethoxyethane; THF: tetrahydrofuran; Bn: benzyl. Grey
row is indicative of optimal conditions.
t
o
(1 mol%) and BuOK (1 mol%) at 135 C in a mixture of toluene and
dimethoxyethane (v/v = 1/1) in a closed system, affording the
desired oxalamide 9a in 26% isolated yield after 24 hours (Table 1,
entry 1). Using the bipyridine-derived catalysts Ru-216 and Ru-3,16
the isolated yield of 9a was improved to 50% (entries 2-3).
Employing the PNNH-based complexes Ru-417 and Ru-517 resulted in
the case of Ru-5 a considerable yield of 9a to 77% using 2 mol% of
tBuOK (entry 5). Encouraged by this promising result, we next
evaluated the solvent effect (entries 6-9). Using toluene as a sole
solvent with Ru-5 as the catalyst 9a was isolated in 86% yield (entry
6). The Dearomatized acridine-based complex Ru-6, previously used
in the esterification of EG,14 only afforded product 9a in 27% yield
With the optimized reaction conditions in hand, we next to
examined the generality of this catalytic dehydrogenative coupling
system using various amines. As shown in Table 2, various aliphatic
amines such as hexan-1-amine (8a), butan-1-amine (8b), pentan-1-
amine (8c), heptan-1-amine (8d), dodecan-1-amine (8e) as well as
2-methoxyethan-1-amine (8f) smoothly dehydrogenatively coupled
with ethylene glycol to give the corresponding oxalamides 9a-9f in
good to excellent isolated yields (66-96%). tert-Butyl (2-
2 | J. Name., 2012, 00, 1-3
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aminoethyl)carbamate (8g) and N1, N1-dimethylpropane-1,3-
diamine (8h) reacted with ethylene glycol forming the desired
compatible with secondary amines as well, as shown in the
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reactions of pyrrolidine and morpholine to fDoOrmI: 1o0x.1a0la3m9/Did0eSC9k02(08695%F
yield) and 9l (83% yield). As a limitation of the system, α-branched
primary amines such as cyclohexanamine (8m), cycloheptanamine
(8n) and (S)-1-phenylethan-1-amine (8o) produced the desired
oxalamide products with lower yields (14-32%). The less
nucleophilic aniline exhibited low reactivity and only delivered
N1,N2-diphenyloxalamide (9p) in 12% yield using 50 mol% of base.
Benzylamines (8q-8v) reacted well, and various electron-
withdrawing (8r-8t) and electron-donating groups (8u-8v) on the
phenyl group did not interfere with the reaction efficiency,
furnishing the desired products 9q-9v in good yields (73-97% yields).
It is worth mentioning that pyridine-containing amine 8w also
worked quite well and the desired product 9w was isolated in 67%
yield. Moreover, oxalamides 3-5 which were reported to act as
ligands3, were obtained in 76-89% yields. Compared to previously
reported methods, this protocol is more atom-economic,
sustainable and efficient.
Table 2. Substrate scopea,b
Ru-5
(1 mol%)
O
O
tBuOK (2 mol%)
HO
H2
+
R
NH2
+
2
OH
R
N
H
N
H
R
Toluene, 135 C
8
9
24 h
O
N
O
N
O
N
O
N
O
O
H
H
H
H
H
N
N
H
9b
O
, 81%
9a
O
9c
O
, 86%
, 96%
O
O
N
O
H
O
N
N
H
H
N
H
H
N
N
H
6
6
O
9f
9e
, 76%
O
9d
O
, 66%
O
, 78%
O
O
N
O
H
N
N
H
H
N
H
N
H
N
H
N
N
BocHN
NHBoc
9i
, 84%
9g
, 53%
9h
, 73%
Amines are an important class of compounds widely used in
agrochemicals, pharmaceuticals and organic synthesis.18
O
O
N
O
O
Hydrogenation of amide bonds represents
a
green and
N
H
N
H
N
H
c
H
straightforward method to access amines. Although efficient
hydrogenation of amides to amines and alcohols catalyzed by
pincer complexes was reported by several groups,19 there is only
one example of catalytic hydrogenation of oxalamides (60 bar
hydrogen gas, 160 °C)7b. Interestingly, the oxalamides synthesized
by us via acceptorless dehydrogenative coupling of EG and amines
could be fully hydrogenated back to the amines and ethylene glycol
using the same catalyst Ru-5. As shown in Table 3, in the presence
9k
, 89%
O
9j
, 70%
O
N
O
O
O
O
N
N
H
N
H
N
H
N
H
O
O
9l
, 83%
O
9m
9n
, 19%
, 32%
O
O
O
O
O
N
H
N
H
N
H
N
H
N
N
H
t
H
of 1 mol% of Ru-5, 4 mol% of BuOK and 40 bar of hydrogen gas at
d
9o
9q
, 14%
O
, 82%
O
9p
12%
135 °C in 2.0 mL of toluene, oxalamides 9a-9d (entries 1-4), 9f, 9i,
9k (entries 5-7), 9q-9v (entries 8-13) and 3-5 (entries 14-16) were
efficiently hydrogenated to form the corresponding amines and
ethylene glycol in excellent yields within 24 hours (85-99% yields).
O
O
O
O
N
H
N
H
N
H
N
H
Cl
N
H
N
H
Cl
9r
9s
9t
, 89%
O
, 89%
O
, 73%
O
F
F
Cl
Cl
Table 3. Hydrogenation of oxalamides to ethylene glycol and
O
O
O
amines
N
H
N
H
MeO
MeO
N
H
N
H
OMe
OMe
N
H
N
H
Ru-5
(1 mol%)
O
O
R
NH2
+
2
8
tBuOK (4 mol%)
N
N
MeO
OMe
R
N
H
N
H
R
9u
9v
, 97%
, 91%
O
9w
, 67%
O
H
2 (40 bar)
HO
OH
Toluene, 135 C, 24 h
3-5, 9
O
O
O
O
N
H
N
H
N
H
N
H
N
H
N
H
O
O
S
S
entrya
9, 3-5
9a
8
yield (%)b
3
4
5
, 76%
, 89%
, 88%
NH2
1
2
3
4
95
95
97
98
8a
NH2
9b
8b
aReaction conditions: ethylene glycol (1.0 mmol), 8 (3.0 mmol), Ru-5
NH2
(1 mol%), BuOK (2 mol%), and toluene (2.0 mL) at 135 oC (bath
t
9c
8c
temperature) for 24 hours. bIsolated yield. A mixture of toluene
c
NH2
(1.0 mL) and dioxane (1.0 mL) was used as the solvent. d50 mol% of
tBuOK was used.
9d
8d
O
5
9f
86
NH2
8f
products in 53% (9g) and 73% (9h) yields. It is worth noting that (−)-
cis-Myrtanylamine (8i) and (+)-Dehydroabietylamine (8j) could also
be applied in this reaction generating oxalamides 9i and 9j in 84%
and 70% yields, respectively. The oxalamidation procedure was
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Upon treatment with 5.0 equivalents of ethylenVieew gAlryticcloe lOntlhinee
above reaction mixture (either from 1.D1OI:e1q0u.1iv0a3l9e/nDt0sSCo0r20625.2F
equivalents of base), a reddish brown solution was formed,
generating complex 11, resulting from ethylene glycol addition to
complex 10. Complex 11 exhibited a broad singlet at δ = 105.71
ppm in the 31P{1H} NMR in THF (Scheme 1b) and in the 1H NMR
spectrum the hydride shifted downfield to – 16.03 ppm (doublet,
2JH-P = 24.0 Hz), consistent with the alkoxide group of EG located
trans to the hydride of complex 11 (see Figure S10 for details). The
IR spectrum of 11 showed a strong carbonyl absorption band at
1899 cm-1 (Figure S14). Upon slow evaporation of a solution of 11 in
a mixture of THF and pentane, crystals suitable for X-ray diffraction
were formed. As shown in Figure 3, a neutral distorted octahedral
complex was generated with the alkoxide group of EG coordinated
to the ruthenium center. Upon heating complex 11 at 110 °C in d8-
toluene for 25 minutes, a new species which gave rise to signal at δ
6
9i
92
NH2
8i
NH 8k
7
8
9k
9q
85
97
NH2
8q
F
9
9r
9s
99
96
NH2
8r
8s
Cl
10
NH2
Cl
1
11
12
13
9t
9u
9v
99
99
99
= 9.59 ppm in the crude H NMR, which might be attributed to the
NH2
8t
formation of glycolaldehyde (see SI, Figure S15 for details).
Interestingly, using complex 11 as a catalyst, the desired product 9a
was isolated in 82% yield, indicating that 11 is a possible catalytic
intermediate (Scheme 1c).
MeO
MeO
NH2
8u
8v
HO
OMe
Cl
(a)
O
P
P
EG
(5.0 eq.)
P
tBuOK
N
Ru CO
N
Ru CO
N
Ru CO
NH2
THF, RT
10 min
P = P(tBu)2
RT, 10 min
N
N
N
H
Bn
H
H
Bn
H
H
Bn
Ru-5
10
11
NH2
14
15
16
3
4
5
95
98
95
8x
(b)
108.81
Ru-5
(bs)
before adding base
1.1 eq. tBuOK
O
S
NH2
NH2
8y
8z
110.75; 110.7
10
(d)
110.76; 110.7
aReaction conditions: oxalamide (0.25 mmol), Ru-5 (1 mol%), tBuOK
(4 mol%), H2 (40 bar) and toluene (2.0 mL) at 135 oC (bath
temperature) for 24 hours. bYields were determined by 1H NMR of
the crude reaction mixture using mesitylene as an internal
standard.
124.0
(bs)
10
(d)
2.2 eq. tBuOK
105.71
then 5.0 eq. EG
11
(bs)
To get some insight into the reaction mechanism, complex Ru-5
was treated with 1.1 equivalents of tBuOK in 0.5 mL of THF at room
temperature (Scheme 1a), resulting in immediate a color change of
the transparent yellow solution to a homogeneous red brown
solution, which exhibited a doublet at δ = 110.73 ppm (2JP-H = 15 Hz)
in the 31P{1H} NMR spectrum in THF (Scheme 2b). Performing the
reaction in d8-THF showed that the N-H proton disappeared and the
two CH2 groups of the P-arm and N-arm were still present, clearly
indicating that the deprotonation took place at the N-H bond and
complex 10 was formed (See SI and Figures S6-9 for details). The
hydride resonance of 10 appeared at δ = – 18.13 ppm (doublet, 2JP-H
(c)
O
N
O
N
HO
11
(1 mol%)
OH
tBuOK (2 mol%)
H
H
+
H
+
2
Toluene, 135 C, 24 h
NH2
8a
9a
82% yield
Scheme 1. (a) Deprotonation of Ru-5 and activation of ethylene
glycol by complex 10 (b) the corresponding 31P{1H} NMR spectra
and (c) the catalytic performance of complex 11.
1
= 40.0 Hz) in the H NMR (see SI, Figure S6 for details). Using 2.2
t
equivalents of BuOK also produced complex 10 together with the
formation of a new species at δ = 124.0 ppm (broad singlet) in the
31P{1H} NMR, attributable to the doubly-deprotonated complex, as
we observed before with the PNNH complex Ru-4.17
4 | J. Name., 2012, 00, 1-3
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alkoxide from 11, followed by hydride abstraction fVrioewmAritticlbeyOntlhinee
ruthenium center;21 the other possibility is that proton and hydride
DOI: 10.1039/D0SC02065F
directly transfer from ethylene glycol to deprotonated complex 10
without the formation of alkoxide 11.22 The hydride elimination
might also occur through the N-side arm dissociation. Subsequently,
hydrogen evolution from complex 15 takes place, followed by
coordination of the generated glycolaldehyde,23 affording the
saturated amido intermediate 16. Reaction of 16 with the amine
forms the hemiacetal intermediate 17 followed by release of α-
hydroxy amide to regenerate the trans-dihydride complex 15. The
formed α-hydroxy amide reacts with another molecule of amine to
form the corresponding oxalamide 9 via a similar pathway. Finally,
complex 15 releases a second molecule of hydrogen, regenerating
complex 10 which then re-enters the catalytic cycle.
Figure 3. X-ray crystal structure of complex 11. Atoms are
presented as thermal ellipsoids at 50% probability level. Hydrogen
atoms are omitted for clarity except the hydride, H2 and H3.
Selected bond lengths (Å) and angles (deg): Ru(1)-C(23), 1.829(19);
Ru(1)-N(1), 2.106(15); Ru(1)-N(2), 2.195(15); Ru(1)-O(2), 2.190(13);
Ru(1)-P(1), 2.280(4); Ru(1)-H, 1.58(3); C(23)-Ru(1)-N(1), 178.10(7);
N(2)-Ru(1)-P(1), 158.90(4); N(1)-Ru(1)-O(2), 80.98(5).
O
R
NH2
HO
9
NHR
NHR
O
HO
O
P
OH
H
P
N
Ru CO
Interestingly, upon treatment EG with 1.0 equivalent of
benzylamine under the optimal conditions, the mono-amidation
product 12 was isolated in 66% yield (Scheme 2a). The α-hydroxy-
amide 12 was also observed in the reaction of EG with two
equivalents of benzylamine (see SI, Figures S16-19 for details).
These results support formation of the oxalamide product via an α-
hydroxyamide intermediate. Moreover, reaction of amide 12 with
hexan-1-amine (8a) afforded the mixed oxalamide 13 in 87% yield
(Scheme 2b). The mixed aryl/alkyl oxamide 14 was also successfully
synthesised using p-anisidine as the arylamine coupling partner
(45% yield). These results highlight the scope of this method for the
synthesis of mixed oxalamides.
N
Ru CO
N
H
H
17
Bn
N
HO
H
H
15
O
Bn
P
R
N
Ru CO
H2
NH2
N
P
H
Bn
11
H
N
Ru CO
HO
O
N
P
H
10
HO
Bn
OH
N
Ru CO
tBuOK
Ru-5
N
H
O
16
Bn
OH
Scheme 3. Proposed reaction mechanism for the ruthenium-
catalyzed acceptorless dehydrogenative coupling of EG and amines
to form oxalamides.
(a)
Ru-5
(1 mol%)
O
tBuOK (2 mol%)
HO
HO
+
H2
+
Ph
NH2
OH
N
H
Ph
Toluene, 135 C, 24 h
8q
(1.0 eq.)
12
66% yield
(b)
O
O
Ru-5
(1 mol%)
12
tBuOK (2 mol%)
+
H2
+
H
N
N
H
Toluene, 135 C, 24 h
Conclusions
NH2
Ph
87% yield
8a
13
(1.5 eq.)
In conclusion, we have developed the acceptorless dehydrogenative
coupling of ethylene glycol and amines with H2 evolution, catalyzed
O
N
O
Ru-5
(1 mol%)
12
by
a ruthenium pincer complex, enabling the synthesis of
tBuOK (2 mol%)
+
H2
OMe
+
H
N
H
oxalamides in an unprecedented highly atom-economic and
sustainable manner. The reverse hydrogenation reaction was also
accomplished, resulting in full hydrogenation of the generated
oxalamides back to the corresponding amines and ethylene glycol,
Toluene, 135 C, 24 h
H2N
OMe
Ph
45% yield
14
8aa
(1.5 eq.)
Scheme 2. Synthesis of the α-hydroxy amide 12 and the mixed
oxalamides 13 and 14.
using the same catalyst.
A plausible catalytic mechanism is
proposed, supported by stoichiometric reactions, NMR studies, X-
ray crystallography as well as the observation of some plausible
intermediates. Further detailed mechanistic investigations and
applications of this methodology are underway.
Based on the experimental results and previous work,8,11 we
propose
a possible reaction mechanism for the ruthenium
homogeneously catalyzed acceptorless dehydrogenative coupling of
ethylene glycol and amines to form oxalamides. As outlined in
t
Scheme 3, deprotonation of Ru-5 by BuOK leads to complex 10,
which adds ethylene glycol to generate the alkoxide species 11 via
metal ligand cooperation.20 Although there is no vacant
coordination site cis to the alkoxide ligand in complex 11, hydride
elimination can take place forming intermediate 15 via two
alternative pathways. One involves the full dissociation of the
Conflicts of interest
There are no conflicts to declare.
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Milstein, Angew. Chem., Int. Ed. 2019, 58, 5105-5109. (e) J.
Acknowledgements
View Article Online
Kothandaraman, S. Kar, R. Sen, A. Goeppert, G. Olah and G. K. S.
DOI: 10.1039/D0SC02065F
This research was supported by the European Research
Council (ERC AdG 692775). D. M. holds the Israel Matz
Professorial Chair of Organic Chemistry. Y.-Q. Z. acknowledges
the Sustainability and Energy Research Initiative (SAERI) of
Weizmann Institute of Science for a research fellowship.
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6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/D0SC02065F
Table of Contents Entry
H2
tBu
tBu
Cl
R
NH2
2
O
O
P
Ru
+
N
Ru CO
R
N
H
N
H
R
HO
H
N
OH
H
Bn
H2
high efficiency
broad substrate scope
atom-economy
reversibility
Ruthenium catalyzed acceptorless dehydrogenative coupling of ethylene glycol and amines to oxalamides is reported. The reverse
hydrogenation reaction was also accomplished.
This journal is © The Royal Society of Chemistry 20xx
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