Oxidative synthesis of amides and pyrroles via dehydrogenative alcohol oxidation by ruthenium diphosphine diamine complexes

Article abstract of DOI:10.1021/om2004755

A series of ruthenium complexes can perform the acceptorless dehydrogenation of diols as well as the reaction of amines and alcohols to form ester, lactam, and amide products. The ligand criteria necessary for high catalytic activity are identified to guide future catalyst development for amide formation from amines and alcohols. These complexes can be employed in a dehydrogenative Paal-Knorr pyrrole synthesis to give 2,5-dimethyl-N- alkylpyrroles.

Full text of DOI:10.1021/om2004755

ARTICLE
pubs.acs.org/Organometallics
Oxidative Synthesis of Amides and Pyrroles via Dehydrogenative
Alcohol Oxidation by Ruthenium Diphosphine Diamine Complexes
Nathan D. Schley, Graham E. Dobereiner, and Robert H. Crabtree*
Department of Chemistry, Yale University, 225 Prospect Street, P.O. Box 208107, New Haven, Connecticut 06520, United States
S Supporting Information
b
ABSTRACT: A series of ruthenium complexes can perform
the acceptorless dehydrogenation of diols as well as the
reaction of amines and alcohols to form ester, lactam, and
amide products. The ligand criteria necessary for high catalytic
activity are identified to guide future catalyst development for
amide formation from amines and alcohols. These complexes can be employed in a dehydrogenative PaalꢀKnorr pyrrole
synthesis to give 2,5-dimethyl-N-alkylpyrroles.
n recent years, a new approach to the synthesis of carboxylic
acid derivatives has been developed which employs the
cyclization of 5-amino-1-pentanol to δ-valerolactam in high yield
in the absence of oxidants.37 Amide formation by 1 proceeds in
good selectivity from a variety of 1,5-amino alcohols but gives
unsatisfactory selectivity and yields with other substrates.
In this report we investigate the contribution of both the
diamine and diphosphine ligands to the activity of the resulting
complexes for the dehydrogenative oxidation of alcohols. A
variety of substrates react under our catalytic conditions, provid-
ing the selective formation of lactams, lactones, amides, and
pyrroles. Complexes incorporating diamine ligands with NꢀH
protons were superior catalysts for amide formation, consistent
with prior computational work identifying an intramolecular
hydrogen bond between amine ligand and bound substrate as a
key factor in hydrogen loss from the metal center.37
I
dehydrogenative coupling of alcohols with other functional
groups.1ꢀ4 The need for atom-economical methods of amide
bond formation has generated a particular interest in the gen-
eration of amides from amines and primary alcohols in the
presence5ꢀ8 or absence9ꢀ15 of a hydrogen acceptor, the most
notable example being the Milstein catalyst.9 The acceptorless
case is especially interesting, because the oxidation of the alcohol
takes place without the need for a stoichiometric oxidant.
Instead, the reaction is driven by the extrusion of H2 gas from
the solution at high temperatures.
The dehydrogenative oxidation of alcohols can be performed
by homogeneous complexes of rhodium,16ꢀ19 ruthenium,20ꢀ26
osmium,21,26 and iridium.27ꢀ29 In the case of ruthenium, accep-
torless oxidation has previously been applied to the conversion of
diols to lactones, as well as the reaction of primary alcohols to
form homocoupled esters.30ꢀ32 Previous attempts at forming
amides via dehydrogenation, however, generally gave alkylated
amines exclusively unless a hydrogen acceptor was present.6
Despite recent progress in the field, acceptorless amide formation
has only been demonstrated in a few specific cases.9ꢀ15 The most
prominent examples feature either specialized pincer ligands9 or
highly donating N-heterocyclic carbene ligands.10ꢀ15 Though
some reports have provided rationales for amide selectivity, these
have so far been ligand specific, and a general mechanistic
framework for the selective synthesis of amides remains elusive.
In order to develop improved catalysts for acceptorless dehy-
drogenation, we have used readily tunable ligand sets. Ruthenium-
(II) diphosphine diamine complexes are a well-studied class of
compounds which have been used extensively in hydrogenation
and transfer hydrogenation reactions,33ꢀ35 but few reports have
explored their use in the dehydrogenative oxidation of alcohols or
determined the aspects of the ligand set which are crucial for
activity.25,36 Our group has previously shown that a ruthenium
diphosphine diamine complex, RuCl2(2-(aminomethyl)pyridine)-
(1,4-bis(diphenylphosphino)butane) (1), catalyzes the oxidative
’ RESULTS
Catalyst Design. In a report examining the conversion of neat
1,4-butanediol to γ-butyrolactone at 205 °C, Hartwig and Zhao
had success with a number of ruthenium(II) compounds.36 We
prepared a family of related ruthenium diphosphine diamines
(Figure 1) and screened the dehydrogenative lactonization
reaction at moderate temperatures in order to select for the most
active catalysts.
From complex 1 as a starting point, we systematically modified
the two principal ligands, the diphosphine and the diamine, to
determine the contribution of each to dehydrogenation activity
and to identify possible ways to improve catalysis. Complex 3 was
prepared to compare the tethered diphosphine dppb of 1 with
two individual triphenylphosphine ligands. 3 has been prepared
previously as both the trans-dichloro and cis-dichloro isomers, and
these have been shown to isomerize from trans to cis in refluxing
toluene.38 The monodentate phosphines in 3 are mutually cis, but
Received: June 2, 2011
Published: July 13, 2011
r
2011 American Chemical Society
4174
dx.doi.org/10.1021/om2004755 Organometallics 2011, 30, 4174–4179
|

Organometallics
ARTICLE
Figure 1. Ruthenium(II) complexes compared for dehydrogenation catalysis.
Figure 2. Crystal structures of 138 (left) and 2 (center), comparing their geometry about the metal center. An alternate view of 2 (right) shows the
distorted P2ꢀRuꢀCl1 angle.
unlike 1, they are not geometrically constrained by a linker and
could isomerize to a trans-diphosphine complex in situ.
Scheme 1. Common Motif for Ligand Bifunctionality in
Hydrogen Transfer from Alcohols
Complex 2 replaces the flexible dppb of 1 with the more rigid
dppf. This diphosphine has a similar bite angle but greatly
reduced flexibility, owing to the incorporation of a metallocene
into the backbone.39 Single-crystal X-ray diffraction on a sample
of 2 confirms the cis-dichloro geometry and affords us an
opportunity to compare the solid-state structures of 138 and 2
(Figure 2). The P1ꢀRuꢀP2 angle in 2 is found to be 97.03(5)°,
substantially larger than the reported bite angle of 92.92(2)° in
1.38 A similar difference can be observed in square-planar
palladium(II) dichloride complexes, where the diphosphines
adopt somewhat larger bite angles: 99.07(5)°40 for dppf and
94.36°41 for dppb. In addition to the difference in bite angle, the
principal structural variation between 2 and 1 is the degree of
steric congestion around the site trans to the primary amine. We
have previously determined that this is the most thermodynami-
cally favored site for a dihydrogen ligand in these systems.37 In
the crystal structure of 2, the P2ꢀRuꢀCl1 angle deviates to
nearly 100°, owing to the projection of the bulky diphosphine
into the axial site (Figure 2, right).
We next prepared several complexes to investigate the role of
the diamine ligand. Our previous computational work on the
mechanism of alcohol dehydrogenation by 1 identified a hydro-
gen-bonding interaction of the aminomethylpyridine ligand with
the substrate as an important factor in stabilizing key intermedi-
ates. However, ruthenium complexes lacking amine ligands have
previously been shown to catalyze alcohol dehydrogenation at
high temperatures.36 Amine ligands containing NꢀH protons
may participate in ligand bifunctionality that serves to greatly
increase rates of hydrogen transfer in certain reactions,42,43 and
this could contribute to a lower barrier to alcohol dehydrogena-
tion (Scheme 1).
secondary diamine N,N0-dimethylethylenediamine were pre-
pared. Complex 5, which lacks an amine ligand, was also
synthesized. Complexes 1-Me2 and 2-Me2 were prepared as
analogues to 1 and 2. Both 1-Me2 and 2-Me2 show a single pair of
doublets in their respective 31P{1H} NMR spectra, indicating
that they are both single isomers in solution. X-ray crystal-
lographic analysis of 1-Me2 and 2-Me2 show that, unlike 1 and
2, both complexes adopt a trans-dichloro arrangement
(Figure 3). Cis/trans isomerism is often seen in complexes of
this type;44 however, 1-Me2 does not isomerize even on heating
in mesitylene for 1 h at 160 °C, suggesting that the trans-dichloro
isomer is thermodynamically preferred. When the synthesis of 1-
Me2 is conducted at room temperature instead of at reflux in
toluene, the same trans isomer is obtained. The geometric
difference between 1, 2 and 1-Me2, 2-Me2 may be significant,
since the inner-sphere pathway for hydride abstraction from an
alcohol requires two cis sites on the catalyst. Calculations on 1
suggest that both inner- and outer-sphere hydride transfer
mechanisms are close in energy, indicating that trans complexes
may still be active for catalysis by an outer-sphere mechanism.
Additionally, the most thermodynamically favorable solid-state
geometry of the dichloride complexes does not necessarily reflect
the preferred geometry of any hydrido45 or alkoxo intermediates
under the catalytic conditions in solution.
In order to test these hypotheses, compounds of the fully
methylated N,N-dimethylaminomethylpyridine and the related
Catalysis. Complexes 1ꢀ5were initially screened for two related
reactions involving alcohol dehydrogenation. The dehydrogenation
4175
dx.doi.org/10.1021/om2004755 |Organometallics 2011, 30, 4174–4179

Organometallics
ARTICLE
Figure 3. ORTEP drawings of crystal structures of 2 (left), 2-Me2 (center), and 1-Me2 (right) with ellipsoids shown at the 50% probability level.
Solvent molecules and hydrogen atoms are omitted for clarity.
Table 1. Comparison of Ruthenium Complexes for the
Dehydrogenation of 1,4-Butanediola
Table 2. Comparison of Ruthenium Complexes for the
Dehydrogenation of N-Butyl-5-amino-1-pentanola
cat.
1
1-Me2
2
2-Me2
3
4
5
cat.
1
1-Me2
2
2-Me2
3
4
5
TOF (hꢀ1
)
10
5.9
12
1.5
5.0
5.0
0.4
TOF (hꢀ1
)
>120
13
>120
23
40
78
9
a Conditions: 2 mmol of diol, 0.10 mmol of KOH, 0.02 mmol of catalyst,
1 mL of toluene. The reaction mixture was heated to 125 °C under a slow
flow of N2 for 4 h. The TOF was determined by the NMR yield of
butyrolactone after 4 h with respect to an internal standard (1,3,5-
trimethoxybenzene).
a Conditions: 1 mmol of amino alcohol, 0.06 mmol of KOH, 0.02 mmol
of catalyst, 1 mL of toluene. The reaction mixture was heated to 125 °C
under a slow flow of N2 for 20 min. The TOF was determined by the
NMR yield of the lactam after 20 min with respect to an internal
standard (1,3,5-trimethoxybenzene).
of 1,4-butanediol to γ-butyrolactone has been used previously to
assess dehydrogenation activity;36 however, we perform the
reaction at a temperature lower than that previously reported.
All compounds tested showed activity in refluxing toluene over
4 h (Table 1), but large differences in apparent rates are seen,
depending on the ligand set. The chelating diphosphine ligand in
1 clearly plays a strong role, as 3 shows a reduced rate. The dppf
derivative 2 proved to be a minor improvement on 1, and both
complexes are significantly more active than all others tested. The
effect of the amine ligand on catalysis is even more profound.
Methylation of the amine (1 vs 1-Me2, 2 vs 2-Me2) is observed to
dramatically decrease the rate of lactone formation from butane-
diol. Complex 5, which lacks the diamine entirely, is nearly
inactive for the dehydrogenative oxidation of the diol, turning
over fewer than 2 times in 4 h.
A useful gauge for the dehydrogenative amide-forming activity
of 1ꢀ5 is the intramolecular conversion of N-butyl-5-amino-1-
pentanol to N-butylvalerolactam. Our previous work has shown
that this substrate is oxidized much more rapidly than the
unsubstituted 5-amino-1-pentanol and the reaction is higher yielding
than the intermolecular reaction of an amine and a primary alcohol.
The rates are presented in turnovers per hour, calculated after
20 min in refluxing toluene (Table 2). Overall this reaction is
much more rapid than the lactone formation reported above. 1
and 2 both display a rate in excess of 120 t.o./h, proceeding to
near completion in 20 min. Their methylated analogues 1-Me2
and 2-Me2 show substantially lower rates: 13 and 23 t.o./h,
respectively.
All four of the complexes containing diamine ligands with NꢀH
protons (1ꢀ4) show rates at least double that of the rates
obtained for those complexes without NꢀH protons (1-Me2 and
2-Me2). Complexes 3 and 1-Me2, which had similar activity in the
oxidation of 1,4-butanediol (Table 1), differ in rate by a factor of 3
for lactam formation, consistent with the ligand NꢀH protons
playing a role in catalysis. A high rate is also obtained for the
secondary diamine diphosphine derivative 4. The lack of the
diphosphine in 3 appears to hinder the activity versus 1 for lactam
formation, just as it does for lactone formation.
Amide Formation. As shown previously, 1 is an excellent
catalyst for the dehydrogenative formation of lactams from 1,5-
amino alcohols but gives low conversion and selectivity when
used for the corresponding intermolecular reaction between an
aliphatic alcohol and amine under similar conditions.37 Subse-
quent experimental work using complex 2 has revealed that the
yield and selectivity depend strongly on the concentration of the
amine component. When the reaction is performed neat in an
excess of the amine, good yields and turnover numbers can be
obtained (Table 3). More hindered or less nucleophilic amines
such as anilines gave poor yields, even under these optimized
conditions. Reactions driven by release of a gas are most often
run in refluxing solvent to reduce the solubility of gaseous
products;46 however, the slow passage of nitrogen gas through
the headspace of the reaction was sufficient to remove hydrogen
even when no component of the reaction was near its boiling
point (Table 3, entry 5).
4176
dx.doi.org/10.1021/om2004755 |Organometallics 2011, 30, 4174–4179

Organometallics
ARTICLE
Table 3. Intermolecular Amide Formation by Complex 2a
Scheme 2. Amide Formation from an Amine and Alcohol
entry
alcohol
amine
loading, %
yield, %b
1
2
3
4
5
6
benzyl alcohol
benzyl alcohol
benzyl alcohol
benzyl alcohol
benzyl alcohol
2-phenethanol
1-hexylamine
1-hexylamine
piperidine
2
4
2
4
4
4
42
74
42
89
58
55
piperidine
1-decylamine
piperidine
a Conditions: 1 mmol of alcohol, 6 mmol of amine, 0.15 mmol of KOH
(4% loading of 2) or 0.1 mmol KOH (2% loading of 2), catalyst loading
with respect to alcohol substrate, heated to 125 °Cfor 3.5h. b Isolated yields
of the corresponding secondary or tertiary amides.
Figure 4. Schematic of hydrogen bonding between a bound hemiam-
inal and either the ligand NꢀH protons or a dihydrogen ligand.37
Table 4. Dehydrogenative Pyrrole Formationa
presence of the primary amine ligand does not appear to have a
large effect on the efficiency of the lactonization reaction, for the
catalytic cyclization of N-butyl-5-amino-1-pentanol the amine
ligand is the most important factor governing reactivity. 1 and 2
turn over more than 40 times in 20 min, respectively, while
complexes 1-Me2 and 2-Me2 are nearly inactive by comparison.
This reaction is thought to proceed by initial oxidation of the
amino alcohol to an amino aldehyde, followed by formation of a
metal-bound hemiaminal and subsequent oxidation to the amide
(Scheme 2). In a previous computational study of 1, we identified
a hydrogen-bonding interaction between a bound hemiaminal
and either a ligand NꢀH proton or a bound dihydrogen ligand
(Figure 4).37 The two isomers were calculated to be close in
energy, but a crucial difference between the two is the magnitude
of the barrier to loss of the dihydrogen ligand from the metal
center. The isomer in which the hemiaminal is hydrogen-bonded
to the amine ligand has a substantially lower barrier for loss of
hydrogen. The difference in the barrier to hydrogen loss could
account for the difference in reaction rate between complexes
containing amine ligands with NꢀH protons and those without.
The high rates of lactam formation by 2 do not extend directly
to the intermolecular case without modification of the condi-
tions. The low yields obtained in the absence of a large excess of
the amine component of the reaction highlight the important
role of the substrate amine in the catalytic cycle. The need for
high concentrations of amine was also observed in a recent report
of amide formation by a ruthenium N-heterocyclic carbene
catalyst.14 From our computational work on the intramolecular
amide bond formation, we suggest that the aldehyde intermedi-
ate must be trapped by the amine while still bound to the metal
center (assuming an inner-sphere pathway) to give a metal-
bound hemiaminal which can undergo further oxidation. If attack
by the amine is slow, as would be the case at lower amine
concentrations or with weakly nucleophilic amines, the aldehyde
can potentially diffuse away and undergo an uncatalyzed imine
condensation, leading to undesired products, or contribute to
catalyst deactivation by decarbonylation.20
entry
amine
cat.
loading, %
yield, %b
1
2
3
4
5
1-hexylamine
1-decylamine
1-decylamine
1-decylamine
1-decylamine
2
2
4
1.5
1.5
1.5
1.5
45
48
46c
37
0
1-Me2
none
a Conditions: 3.0 mmol of 2,5-hexanediol, 2.5 mmol of amine, 0.23
mmol of sodium formate, catalyst loading with respect to amine
substrate. The reaction mixture was heated to 125 °C under a slow
flow of N2 for 16 h. b Isolated yields of pyrrole. c NMR yield with respect
to an internal standard (1,3,5-trimethoxybenzene).
Pyrrole Synthesis. In our previous report examining 1,
imines were sometimes obtained as byproducts of amide
formation by condensation of the amine with aldehyde gener-
ated in situ.37,47 By using a secondary alcohol in place of a
primary alcohol, we could selectively generate ketimines and employ
them in the oxidative synthesis of N-heterocycles. We have found
that the dehydrogenative oxidation of 2,5-hexanediol by a suitable
catalyst in the presence of a primary alkylamine gives the N-alkyl-2,5-
dimethylpyrroles in a dehydrogenative PaalꢀKnorr pyrrole synth-
esis (Table 4). Several of the catalysts tested gave similar yields with
the same loading, and increased catalyst loading did not result in
additional product being formed. This reaction likely proceeds by
metal-catalyzed oxidation of the diol to the dione followed by a
series of uncatalyzed condensation reactions leading to the pyrrole
product.48 Sodium formate gave better results than potassium
hydroxide when used as an activator for the ruthenium complexes
in this reaction, and other formate salts tested were comparable,
including cesium formate and zinc formate. The primary diol 1,4-
butanediol gave less satisfactory results under the same conditions,
as a myriad of products including the pyrrole, imide,49 and lactone
were formed competitively.
The superior activity of 1 and 2 versus that of other complexes
tested highlights the importance of both the diphosphine and
primary aminomethylpyridine ligand in the determining the rate
of dehydrogenative catalysis. Minor changes such as employing
two monophosphines instead of the diphosphine or methylation
of the diamine ligand result in profoundly lower rates, particularly
’ DISCUSSION
The chelating aminomethylpyridine ligand appears to have a
crucial role in certain reactions presented above. Though the
4177
dx.doi.org/10.1021/om2004755 |Organometallics 2011, 30, 4174–4179

Organometallics
ARTICLE
in lactam formation. As the factors which enable ruthenium
complexes to catalyze dehydrogenative amide formation are still
not well understood, subsequent work on new catalysts could
usefully benefit from this study by incorporation of bulky diphos-
phines and amine ligands which are capable of acting as hydrogen
bond donors for bound substrates.
solution. 1H NMR (500 MHz, CD2Cl2): δ 8.33 (d, J = 5.2 Hz, 1H), 7.84
(t, J = 8.2 Hz, 4H), 7.74 (t, J = 8.3 Hz, 4H), 7.43 (td, J = 7.6, 1.5 Hz, 1H),
7.34ꢀ7.28 (m, 2H), 7.28ꢀ7.19 (m, 6H), 7.14ꢀ7.07 (m, 5H), 6.58 (t, J =
6.3 Hz, 1H), 4.26 (br s, 2H), 2.99ꢀ2.80 (m, 4H), 2.10 (s, 6H), 1.71 (br s,
4H). 31P NMR (202 MHz, CD2Cl2): δ 39.43 (d, J = 40.0 Hz), 29.20 (d,
J = 40.8 Hz). 13C NMR (126 MHz, CD2Cl2): δ 157.34, 140.47 (d, J = 34.4
Hz), 139.33 (d, J = 36.5 Hz), 136.18, 134.53 (d, J = 8.1 Hz), 134.35 (d, J =
8.1 Hz), 129.18, 127.89 (d, J = 8.3 Hz), 127.73 (d, J = 8.6 Hz), 121.71,
121.19, 71.78, 51.11, 27.76 (d, J = 27.1 Hz), 27.18 (d, J = 27.4 Hz), 23.71
(d, J=3.3 Hz),22.73 (d, J=2.7Hz). Anal. Calcdfor C36H40Cl2N2P2Ru: C,
58.86; H, 5.49; N, 3.81. Found: C, 59.09; H, 5.48; N, 3.70.
’ CONCLUSIONS
A variety of ruthenium diamine diphosphine complexes have
been shown to catalyze the dehydrogenative oxidation of diols to
lactones and amino alcohols to lactams. The most active catalyst
tested can convert primary alcohols and amines to amides,
operating best under conditions with excess of the amine compo-
nent. Complexes containing amine ligands with NꢀH protons are
superior catalysts, possibly due to a hydrogen-bonding interaction
between the ligand and bound substrate which lowers the barrier
to hydrogen loss from the metal. The future design of catalysts for
net dehydrogenative processes may well benefit from considera-
tion of hydrogen-bonding interactions in proposed catalytic inter-
mediates beyond the initial dehydrogenation step.
trans-RuCl2(dppf)(2-(N,N-dimethylamino)methylpyridine)
(2-Me2). Complex 2-Me2 was prepared by variation on the published
procedure forcomplex 1.38 A flame-dried100mLSchlenk flaskwas placed
under nitrogen and RuCl2(PPh3)4 (0.663 g, 0.543 mmol) and 2-(N,N-
dimethylamino)methylpyridine (0.100 g, 0.734 mmol) were added,
followed by 25 mL of dry, degassed toluene. The mixture was heated to
110 °C for 1 h and then cooled. 1,10-Bis(diphenylphosphino)ferrocene
(0.302 g, 0.545 mmol) was then added at once, and the reaction mixture
was heated to 110 °C for an additional 19 h. After the flask had cooled to
room temperature, 50 mL of degassed pentane was added. The solution
was cooled in an ice bath and then filtered quickly in air. The deep orange
supernatant was reduced to approximately 10 mL on a rotary evaporator,
treated with an additional 50 mL of pentane, and then filtered once again
to afford the product as an orange solid. Yield: 0.292 g (62%). Crystals
suitable for X-raydiffraction weregrown bydiffusion of diethyl ether intoa
saturated benzene solution. The product is relatively insensitive to air and
can be handled in solution for a period of minutes to hours without
decomposition. The NMR spectra of 2-Me2 are broad at room tempera-
ture; therefore, the spectra were recorded at ꢀ20 °C in order to resolve
the coupling constants. 1H NMR (500 MHz, CD2Cl2, ꢀ20 °C): δ 9.56
(m, 1H), 8.37 (dd, J = 11.8, 8.2 Hz, 1H), 7.85 (d, J = 5.8 Hz, 1H), 7.65 (t,
J = 8.9 Hz, 1H), 7.61 ꢀ 7.55 (m, 2H), 7.50 ꢀ 7.06 (m, 14H), 6.99 (t, J =
7.6 Hz, 1H), 6.84 (t, J = 7.5 Hz, 1H), 6.62 (t, J = 8.4 Hz, 1H), 6.56 (t, J =
7.6 Hz, 1H), 6.45 (t, J = 6.6 Hz, 1H), 5.97 (1H), 5.58 (d, J = 14.1 Hz, 1H),
5.05 (1H), 4.58 (1H), 4.28 (1H), 4.21 (1H), 3.97 (1H), 3.92 (dd, J = 3.7,
2.4 Hz, 1H), 2.95 (d, J = 3.1 Hz, 1H), 2.93 (s, 1H), 2.58 (s, 3H), 1.59 (s,
3H). 31P NMR (202 MHz, CD2Cl2, ꢀ20 °C): δ 48.12 (d, J = 38.3 Hz),
30.09 (d, J = 38.3 Hz). Anal. Calcd for C42H40Cl2N2P2FeRu: C, 58.48; H,
4.67; N, 3.25. Found: C, 58.91; H, 4.89; N, 3.43.
’ EXPERIMENTAL SECTION
RuCl2(2-aminomethylpyridine)(dppb) (1),38 RuCl2(2-aminomethyl-
pyridine)(dppf) (2),25 RuCl2(PPh3)2(2-aminomethylpyridine) (3),38
RuCl2(N,N0-dimethylethylenediamine)(dppf) (4),35 RuCl2(PPh3)-
(dppb) (5),50 and N-butyl-5-amino-1-pentanol37 were prepared ac-
cording to the literature procedures. All solvents were of commercial
grade and dried over activated alumina using a Grubbs-type solvent
purification system prior to use.51 NMR spectra were recorded on a 400
or 500 MHzBrukeror Varianspectrometer andreferencedtotheresidual
solvent peak (δ in ppm and J in Hz). Elemental analyses were performed
by Atlantic Microlabs Inc. (Norcross, GA). Crystals of 2 suitable for X-ray
diffraction were grown by diffusion of diethyl ether into a saturated
methylene chloride solution.
2-(N,N-Dimethylamino)methylpyridine.52 2-Aminomethyl-
pyridine (4.0 mL, 39 mmol) was combined with formic acid (7.2 mL,
190 mmol) and formaldehyde (37 wt %, 8.8 mL, 120 mmol) under
nitrogenin a 50 mLround-bottom flaskwith anattached refluxcondenser.
The reaction mixture was heated to reflux for 18 h and then cooled and
treated with a 2 M NaOH solution to liberate the free base. The solution
was extracted with four 150 mL portions of methylene chloride, and the
combined organic layers were dried over MgSO4 and concentrated on a
rotary evaporator to yield a dark brown oil. Chromatography on basic
alumina (Aldrich, Brockmann I, standard grade) with 20% EtOAc/80%
hexanes gave the pure product as a yellow oil. Yield: 2.60 g (49%). 1H
NMR (400 MHz, CDCl3): δ 8.56 (d, J = 4.2 Hz, 1H), 7.66 (m, 1H), 7.38
(d, J = 7.8 Hz, 1H), 7.16 (m, 1H), 3.58 (s, 2H), 2.29 (s, 6H).
’ ASSOCIATED CONTENT
S
Supporting Information. Text, tables, figures, and CIF
b
files giving catalytic procedures, characterization data for the
products of catalysis, and details of the X-ray analysis of 1-Me2, 2,
and 2-Me2. This material is available free of charge via the
Internet at http://pubs.acs.org.
trans-RuCl2(dppb)(2-(N,N-dimethylamino)methylpyridine)
(1-Me2). Complex 1-Me2 was prepared by variation of the published
procedure for complex 1.38 A flame-dried 50 mL Schlenk flask was placed
under nitrogen, and RuCl2(PPh3)4 (0.832 g, 0.681 mmol) and 2-(N,N-
dimethylamino)methylpyridine (0.115 g, 0.844 mmol) were added,
followed by 10 mL of dry, degassed toluene. The mixture was heated
to 105 °C for 1 h and then cooled. 1,4-Bis(diphenylphosphino)butane
(0.290 g, 0.680 mmol) was then added at once, and the reaction mixture
was heated to 110 °C for an additional 19 h. After the flask had cooled to
room temperature, 40 mL of degassed pentane was added. The resulting
precipitate was collected by vacuumfiltrationin air, washedwith10 mLof
diethyl ether, and then dried in vacuo to give the product as a pure orange
solid. Yield: 0.380 g (76%). Crystals suitable for X-ray diffraction were
grown by diffusion of diethyl ether into a saturated benzene solution. The
product is stable to air in the solid state but is somewhat sensitive to air in
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: robert.crabtree@yale.edu.
’ ACKNOWLEDGMENT
We acknowledge funding from the Division of Chemical
Sciences, Geosciences, and Biosciences, Office of Basic Energy
Sciences of the U.S. Department of Energy, through Grant DE-
FG02-84ER13297. We thank Dr. Ainara Nova (Institute of
Chemical Research of Catalonia, Tarragona, Spain) and Prof.
Odile Eisenstein (Universitꢀe Montpellier 2, Montpellier, France)
for valuable discussions.
4178
dx.doi.org/10.1021/om2004755 |Organometallics 2011, 30, 4174–4179

Organometallics
ARTICLE
’ REFERENCES
(38) Baratta, W.; Herdtweck, E.; Siega, K.; Toniutti, M.; Rigo, P.
Organometallics 2005, 24, 1660–1669.
(39) Kranenburg, M.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Eur.
J. Inorg. Chem. 1998, 25–27.
(40) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158–163.
(41) Makhaev, V. D.;Dzhabieva, Z. M.;Konovalikhin, S. V.;Dyachenko,
O. A.; Belov, G. P. Koord. Khim. 1996, 22, 598–602.
(42) Samec, J. S. M.; Backvall, J. E.; Andersson, P. G.; Brandt, P.
Chem. Soc. Rev. 2006, 35, 237–248.
(43) Abdur-Rashid, K.; Clapham, S. E.; Hadzovic, A.; Harvey, J. N.;
Lough, A. J.; Morris, R. H. J. Am. Chem. Soc. 2002, 124, 15104–15118.
(44) Queiroz, S. L.; Batista, A. A.; Oliva, G.; do, Pi.; Gambardella,
M. T.; Santos, R. H. A.; MacFarlane, K. S.; Rettig, S. J.; James, B. R. Inorg.
Chim. Acta 1998, 267, 209–221.
(45) Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough,
A. J.; Morris, R. H. J. Am. Chem. Soc. 2005, 127, 1870–1882.
(46) Aoki, T.; Crabtree, R. H. Organometallics 1993, 12, 294–298.
(47) Gnanaprakasam, B.; Zhang, J.; Milstein, D. Angew. Chem., Int.
Ed. 2010, 49, 1468–1471.
(48) Amarnath, V.; Anthony, D. C.; Amarnath, K.; Valentine, W. M.;
Wetterau, L. A.; Graham, D. G. J. Org. Chem. 1991, 56, 6924–6931.
(49) Zhang, J.; Senthilkumar, M.; Ghosh, S. C.; Hong, S. H. Angew.
Chem., Int. Ed. 2010, 49, 6391–6395.
(50) Jung, C. W.; Garrou, P. E.; Hoffman, P. R.; Caulton, K. G. Inorg.
Chem. 1984, 23, 726–729.
(1) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev. 2010, 110,
681–703.
(2) Guillena, G.; Ramon, D. J.; Yus, M. Chem. Rev. 2010, 110,
1611–1641.
(3) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J. Dalton Trans.
2009, 753–762.
(4) Hamid, M.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal.
2007, 349, 1555–1575.
(5) Zweifel, T.; Naubron, J. V.; Grutzmacher, H. Angew. Chem., Int.
Ed. 2009, 48, 559–563.
(6) Naota, T.; Murahashi, S. I. Synlett 1991, 693–694.
(7) Watson, A. J. A.; Maxwell, A. C.; Williams, J. M. J. Org. Lett. 2009,
11, 2667–2670.
(8) Fujita, K.; Takahashi, Y.; Owaki, M.; Yamamoto, K.; Yamaguchi,
R. Org. Lett. 2004, 6, 2785–2788.
(9) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317,
790–792.
(10) Nordstrom, L. U.; Vogt, H.; Madsen, R. J. Am. Chem. Soc. 2008,
130, 17672.
(11) Ghosh, S. C.; Muthaiah, S.; Zhang, Y.; Xu, X. Y.; Hong, S. H.
Adv. Synth. Catal. 2009, 351, 2643–2649.
(12) Muthaiah, S.; Ghosh, S. C.; Jee, J.-E.; Chen, C.; Zhang, J.; Hong,
S. H. J. Org. Chem. 2010, 75, 3002–3006.
(13) Zhang, Y.; Chen, C.; Ghosh, S. C.; Li, Y. X.; Hong, S. H.
Organometallics 2010, 29, 1374–1378.
(14) Prades, A.; Peris, E.; Albrecht, M. Organometallics 2011, 30,
1162–1167.
(15) Ghosh, S. C.; Hong, S. H. Eur. J. Org. Chem. 2010, 4266–4270.
(16) Charman, H. B. J. Chem. Soc. B 1970, 584–587.
(17) Morton, D.; Cole-Hamilton, D. J. J. Chem. Soc., Chem. Commun.
1987, 248–249.
(51) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518–1520.
(52) Fischer, A.; King, M. J.; Robinson, F. P. Can. J. Chem. 1978,
56, 3059–3067.
(18) Shinoda, S.; Kojima, T.; Saito, Y. J. Mol. Catal. 1983, 18, 99–104.
(19) Matsubara, T.; Saito, Y. J. Mol. Catal. 1994, 92, 1–8.
(20) Jung, C. W.; Garrou, P. E. Organometallics 1982, 1, 658–666.
(21) Dobson, A.; Robinson, S. D. Inorg. Chem. 1977, 16, 137–142.
(22) Morton, D.; Cole-Hamilton, D. J. J. Chem. Soc., Chem. Commun.
1988, 1154–1156.
(23) Ligthart, G. B. W. L.; Meijer, R. H.; Donners, M. P. J.; Meuldijk,
J.; Vekemans, J. A. J. M.; Hulshof, L. A. Tetrahedron Lett. 2003, 44,
1507–1509.
(24) Adair, G. R. A.; Williams, J. M. J. Tetrahedron Lett. 2005,
46, 8233–8235.
(25) Baratta, W.; Bossi, G.; Putignano, E.; Rigo, P. Chem. Eur. J.
2011, 17, 3474–3481.
(26) Bertoli, M.; Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.;
Gusev, D. G. Organometallics 2011, 30, 3479–3482.
(27) Lin, Y.; Ma, D.; Lu, X. Tetrahedron Lett. 1987, 28, 3115–3118.
(28) Fujita, K.; Tanino, N.; Yamaguchi, R. Org. Lett. 2007,
9, 109–111.
(29) Prades, A.; Corberꢀan, R.; Poyatos, M.; Peris, E. Chem. Eur. J.
2008, 14, 11474–11479.
(30) Murahashi, S.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J. Org.
Chem. 1987, 52, 4319–4327.
(31) Murahashi, S. I.; Ito, K. I.; Naota, T.; Maeda, Y. Tetrahedron
Lett. 1981, 22, 5327–5330.
(32) Blum, Y.; Shvo, Y. J. Organomet. Chem. 1985, 282, C7–C10.
(33) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa,
M.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R. Angew. Chem.,
Int. Ed. 1998, 37, 1703–1707.
(34) Abdur-Rashid, K.; Lough, A. J.; Morris, R. H. Organometallics
2000, 19, 2655–2657.
(35) Ma, G.; McDonald, R.; Ferguson, M.; Cavell, R. G.; Patrick,
B. O.; James, B. R.; Hu, T. Q. Organometallics 2007, 26, 846–854.
(36) Zhao, J.; Hartwig, J. F. Organometallics 2005, 24, 2441–2446.
(37) Nova, A.; Balcells, D.; Schley, N. D.; Dobereiner, G. E.;
Crabtree, R. H.; Eisenstein, O. Organometallics 2010, 29, 6548–6558.
4179
dx.doi.org/10.1021/om2004755 |Organometallics 2011, 30, 4174–4179