Ruthenium-catalyzed deaminative redistribution of primary and secondary amines

Article abstract of DOI:10.1039/c7dt02470c

A ruthenium-hydride complex, [Ru(H)(Cl)(CO)(PCy₃)₂], was found to be active in the highly selective redistribution of primary and secondary amines bearing an α-hydrogen atom. This new deaminative coupling of amines enables the highly selective synthesis of secondary amines from primary amines and of tertiary amines from secondary amines with the evolution of ammonia. A preliminary mechanistic view of this novel reaction based on catalytic experiments using NMR methods confirms the synthetic observations.

Full text of DOI:10.1039/c7dt02470c

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Ruthenium-catalyzed deaminative redistribution of primary and
secondary amines
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a,b
S. Kostera, B. Wyrzykiewicz, P. Pawluć, and B. Marciniec *
DOI: 10.1039/x0xx00000x
www.rsc.org/
3 2
A ruthenium-hydride complex: [Ru(H)(Cl)(CO)(PCy ) ] was found to found to be active in the splitting of secondary or tertiary
be active in the highly selective redistribution of primary and amines to primary amines as predominant products using NH
3
secondary amines bearing an α-hydrogen atom. This new (Scheme 1, eq. 3). The splitting of secondary amines is
deaminative coupling of amines enables highly selective synthesis expected to proceed via the ‘hydrogen shuttling’ concept; as it
of secondary amines from primary amines and of tertiary amines concerns dehydrogenation of the secondary amine,
from secondary amines with evolution of ammonia. Preliminary condensation with ammonia and then rehydrogenation of the
[10-11]
mechanistic view of this novel reaction based on catalytic resulting imine to give primary amine.
experiments using NMR methods confirms the synthetic
observations.
In the course of our recent studies on the ruthenium-
catalyzed N-silylation of primary and secondary amines with
substituted vinylsilanes, leading to formation of silylamines
[13]
Amines are valuable building blocks for fine chemical industry
including medicinal, pharmaceutical, agrochemical and
with evolution of ethylene,
we have observed that in the
] complex
absence of vinylsilane, the [Ru(H)(Cl)(CO)(PCy )
3 2
[1]
material chemistry. Secondary and tertiary amines have
found many applications, including: surfactants, flotation
agents, gasoline detergents, corrosion inhibitors, rubber
processing additives, emulsifiers for herbicides, textile
softeners etc. Thus, the development of new catalytic methods
for the synthesis of amines has attracted much attention and
continues to be an active area of research.
promoted unexpected redistribution of amines to form amines
of higher order. Here, we report a new type of highly selective
catalytic transformation of primary and secondary amines
leading to secondary or tertiary amines, respectively, (Scheme
1
eq. 4-5) in the presence of ruthenium(II)-hydride complex.
Oxidative coupling of amines proceeding in the presence of
homogeneous and heterogeneous catalysts has been widely
studied during the last decade. The oxidative homo-coupling of
primary amines (Scheme 1, eq. 1) and the oxidative
dehydrogenation of secondary amines (Scheme 1, eq. 2)
enable the synthesis of imines, which are versatile
intermediates in organic synthesis. Both transition metal
[
2]
[3]
[4]
[5]
[6]
[4c, 6a, 6c]
complexes (V, Mn, Fe, Os, Ru, Rh
) and mixed
[
catalyst systems have been used in these processes. Also
[9]
hydrogen peroxide or water can serve as source of oxygen.
7]
[8]
[
10]
[11]
On the other hand, Beller
and Vogt
have recently
reported that a ruthenium-based half sandwich complex
[12]
Scheme 1 Oxidative coupling vs. redistribution of amines
(Shvo’s catalyst) used in amine racemization reaction
was
We chose the splitting of di(n-butyl)amine as a model reaction
for our investigation since the products of its redistribution can
be easily observed using the GC-MS method. First, we
examined different ruthenium(II) and ruthenium(0) catalytic
a.
b.
Faculty of Chemistry, Adam Mickiewicz University in Poznań, Umultowska 89b,
1-614 Poznań, Poland Address here.
Center for Advanced Technologies, Adam Mickiewicz University in Poznań,
Umultowska 89c, 61-614 Poznań, Poland.
Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
6
†
systems: [Ru(H)(Cl)(CO)(PCy
3
)
2
] (
1
), [Ru(H)(Cl)(CO)(PPh
3
)
3
] (
(
2
),
),
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
[
Ru(Cl) (PPh ) ]
2
(3),
[Ru (CO) ]
3 12
4
3 3
+
-
Ru(H)(CO)(MeCN) (PCy ) ] [BF ] (
[
5) and [Ru(H)(Cl)(PPh ) ] (
3 3
6)
2
3 2
4
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using 1 mmol of di(n-butyl)amine, 0,5 mmol anthracene, 5 new signal at 0.17 ppm was detected, which can be assigned
o
mol% of catalyst, at 120 C (Table 1). All manipulations were to ammonia molecule, which is in line with literature data
[14]
performed under argon atmosphere using Schlenk bomb flask (SI).
fitted with a plug valve as the reaction vessel. After several In the above-optimized conditions, we investigated the scope
attempts we have found that the reaction of (n-Bu) NH in the of this reaction, using various secondary amines (Scheme 2).
2
presence of ruthenium precursors 1-6 performed in toluene in These results are summarized in Table 2.
o
a closed system at 120 C afforded selectively the amine
3
coupling product – (n-Bu) N after 24 h, in moderate to good
yields (Table 1).
Scheme 2 Redistribution of secondary amines
2
Table 1 The results of catalyst screening in the redistribution of (n-Bu) NH
Aliphatic amines, which are known to readily undergo self-
coupling, showed the highest reactivity in the presence of
catalyst 1. Simple secondary amines (Table 2, entries 1-2) are
b
Catalyst
(n-Bu) N yield [%]
3
converted to the tertiary amines in good yields (85-89%) and
excellent selectivities (100%), however, redistribution of di(n-
octyl)amine required a longer reaction time (72 h) and
proceeded with lower conversion (49%). Similarly,
dibenzylamine (Table 2 entry 4) seems to be less reactive
under given conditions. As the results show, the maximum
conversion reached was limited in all cases, which might be
due to catalyst deactivation, when extending the heating time
does not significantly affect the progress of the reaction.
We found that ruthenium-catalyzed redistribution of amines
occurred efficiently also when primary amines were applied as
coupling substrates and the reactions led to the formation of
secondary amines with evolution of ammonia (Scheme 3).
[
Ru(H)(Cl)(CO)(PCy
3
)
2
] (1)
] (2)
85
[Ru(H)(Cl)(CO)(PPh
3
)
3
20
50
70
15
24
[
Ru(Cl)
Ru
Ru(H)(CO)(MeCN)
Ru(H)(Cl)(PPh
Reaction conditions: [(n-Bu)
2
(PPh
3
)
3
] (3)
a
[
3
(CO)12] (4)
(PCy
+
-
[
2
3
)
2
] [BF
4
] (5)
[
3 3
)
] (6)
o
a
2
b
NH]:[Ru] = 20:1, 120 C, 24 h, 15 mol%
calculated to ruthenium, calculated by GC, internal standard
anthracene, solution concentration - 0.07 M, amine – 0.138 mmol,
toluene 2 mL, anthracene (0.069 mmol)
–
These results indicate that ruthenium(II)-hydride complex
exhibited the highest catalytic activity from among the tested
group of ruthenium promoters, however all of the tested
ruthenium complexes 1-6 showed the ability to catalyze amine
redistribution with at least fairly good effects. All reactions
1
Scheme 3 Redistribution of primary amines
n-Butylamine and isopropylamine reacted successfully to give
yielded (n-Bu)
formation of primary amine (n-butylamine) was not observed
under applied conditions. Reaction of (n-Bu) NH in the
3
N as a single reaction product and the
(
n-Bu) NH and (i-Pr) NH respectively, in high yields (84-85%)
2 2
and excellent selectivity (Table 2, entry 5-6) but did not
undergo further coupling to give tertiary amines as we
expected, which is most likely due to the deactivation of
catalyst by ammonia. This is in line with previously reported
ruthenium catalyzed conversion of primary amines to
2
o
presence of 3 mol% of
1 conducted at 120 C caused a
decrease in amine conversion to 30% after 24h. No reaction
occurred at 80 °C and only a slight substrate conversion (~10%)
was observed after 24 h, while heating the reactants to 100 °C.
[15]
secondary amines under harsh conditions . However,
The best results were obtained when using diluted (0.07 M)
o
at 120 C.
addition of extra portion (5 mol%) of catalyst
1 to the post-
solution of amine and 5% of ruthenium catalyst
1
reaction mixture (performed for n-hexylamine) and heating to
o
20 C resulted in the formation of tertiary amine after 24 h
This result shows that when a donating phosphine increase the
electron density of the metal center, the reaction is more
efficient, which seems to prove that the oxidative addition
may be favored. To the best of our knowledge, this is a novel
deaminative coupling of amines proceeding in the presence of
ruthenium complexes.
1
(Scheme 4).
To confirm the formation of tertiary amine from secondary
1
Scheme 4 Redistribution of n-hexylamine to tri(n-hexyl)amine
13
one, we performed H NMR and C NMR monitoring of the
reaction of diethylamine with complex
(20:1 ratio) under Redistribution of branched primary amines: 5-methylhexan-2-
1
established conditions. Increasing conversion of diethylamine amine and 2-ethylhexylamine occurred with high conversions
towards triethylamine can be clearly observed over time in the (88-94%), however, in the case of the 2-ethylhexylamine (Table
1
H NMR spectrum. No side by-products have been observed. 2, entry 9), cyclization side product (2-ethyl-1-(2-ethylhexyl)-6-
While the reaction mixture was heated, the appearance of a methylpiperidine) was also obtained. Interestingly, the
2
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redistribution of aniline did not occur even after prolonged and GC-MS methods to gain mechanistic insights into the
o
keeping at 120 C, whereas benzylamine was converted to catalytic reaction. The reaction of PhCH
2
NH
in toluene-d
butylamine did not undergo redistribution. This demonstrates monitored by H NMR analysis. Addition of amine to complex
the important role played by α-CH group in the mechanism of at room temperature caused the disappearance of the signal
2
with equimolar
dibenzylamine in 62% yield within 24 h. Aniline and t- amount of complex [Ru(H)(Cl)(CO)(PCy
3
)
2
]
1
8
was
1
1
the process. .
at -24.30 ppm, originating from the ruthenium-hydride
complex 1, after only 5 minutes. The color of the reaction
mixture changed from pale-yellow to green and the
Table 2 Redistribution of secondary and primary amines in the presence
of catalyst 1
appearance of a new ruthenium-hydride peak at -14.34 ppm
1
t, JPH = 23.2 Hz) was detected by H NMR. The peak was
(
Product
yield [%]/
assigned to hexacoordinated ruthenium-hydride complex
containing PhCH NH as a ligand. Heating the reaction mixture
Conversion of
amine [%]
Entry
Amine
Time [h]
2
2
(isolated)
o
at 120 C changed its color to orange. A slight shift of
ruthenium-hydride signal was observed during the reaction
progress, which suggests the formation of a new ruthenium-
hydride complex (-14.23 ppm (t), JPH = 22.6 Hz). Further
heating causes the decay of the latter and formation of
another ruthenium-hydride complex (-13.91 ppm (t) JPH = 22.1
Hz) (for details please see SI).
1
2
3
4
5
6
7
8
9
Et NH
86
24
24
72
72
48
48
24
72
85 (79)
89 (82)
48 (40)
15
2
8
9
2
Bu NH
49
2
Oc NH
1
5
(PhCH ) NH
2 2
85
85
62
0
84 (76)
85 (75)
62 (55)
-
n-BuNH2
The plausible simplified mechanism of redistribution of amines
proposed for ruthenium(II)-chloride complexes is given in
Scheme 5.
i
PrNH2
PhCH NH2
2
PhNH2
2
-ethyl-
a
94
88
0
24
24
48
66
hexylamine
-methylhexan-2-
5
1
1
0
1
88 (80)
-
amine
t
BuNH
2
o
Reaction conditions: toluene, 120 C. Catalyst 1 loading 5 mol%, amine
concentration - 0.07 M Yield calculated by GC and GC-MS, internal
standard – anthracene (entry 1, 2, 5, 6, 8, 11) or dodecane (entry 3, 4, 7,
a
9
,
10) 29% of cyclization product
-
2-ethyl-1-(2-ethylhexyl)-6-
methylpiperidine
The products of the reactions (tertiary or secondary amines)
were detected by GC and GC-MS by comparison with
chromatograms of commercial products. Selected products
were isolated and their structures were confirmed by using
NMR analysis (see SI).
The cross-coupling reactions of secondary and primary amines
in the presence of catalyst
selectivity of their redistribution. Cross-coupling of two
secondary amines (1:1 molar ratio) i. e. (PhCH NH (64%
conversion) and (n-Bu) NH (99% conversion) afforded
unsymmetrically substituted secondary amine: (n-
Bu)(PhCH )NH (25% yield) accompanied by a mixture of three
tertiary amines: (n-Bu) N (11% yield), (n-Bu) (PhCH )N (17%)
and (n-Bu)(PhCH N (7%). Higher selectivity was observed in
the cross-coupling of (n-Bu) NH with aniline, since the latter
does not undergo homo-coupling. Aniline reacted successfully
with (n-Bu) NH (conversion of both amines higher than 92%) in The proposed reaction mechanism involves the coordination
the presence of catalyst to form the secondary amine: Ph(n- of amine to complex as the initial step. Addition of amine
Bu)NH and (n-Bu) N at the ratio 3:1 (for details of cross- and maintaining the reaction mixture at 120 °C led to reductive
coupling products analysis please see SI). elimination of HCl from complex in the form of amine
All the catalytic measurements performed were followed by hydrochloride to yield complex similarly to the mechanism
stoichiometric study of complex with substrates using NMR previously reported for ruthenium-catalyzed N-alkylation of
1 was also performed to check the
2 2
)
2
2
3
2
2
2
)
2
Scheme 5 Proposed mechanism of ruthenium-catalyzed
redistribution of amines
2
2
1
1
3
2
3
1
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[
16]
[17]
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and dehydrogenation of amines to nitriles
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1
Ruthenium-amido complex
3
initiates the catalytic reaction via
subsequent β-hydride elimination from an α-CH group of
amido ligand to ruthenium, which generates ruthenium-
hydride complex with coordinated imine as a ligand (complex
7
7
4
). Alternatively, ruthenium-amido complex can be formed via
oxidative addition of amine to ruthenium precursor. Indeed,
stoichiometric reaction of [Ru(Cl) (PPh ] with diethylamine
2
1
, 13181-13185; (i) P. Sudarsanam, B. Hillary, M. H. Amin, S.
B. A. Hamid, S. K. Bhargava, Appl Catal B. 2016, 185, 213-
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2
amido ligand (-17.60 ppm (q) JPH = 25.7 Hz), similarly to the
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[18]
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Coordination of the next molecule of amine (complex ) and
its attack to imine ligand generates complex containing imine
.
5
8
9
6
coupling product as a ligand with elimination of ammonia
according to the mechanism proposed for dehydrogenative
[17]
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1
1
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previously applied in the N-silylation of amines with
vinylsilanes is also an active catalyst in the selective
redistribution of primary and secondary amines to give amines
of higher order with evolution of ammonia. Both primary and
secondary aliphatic amines bearing an α-hydrogen atom were
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