A practical and effective ruthenium trichloride-based protocol for the regio- and stereoselective catalytic hydroamidation of terminal alkynes

Article abstract of DOI:10.1002/adsc.200800508

A rational catalyst development based on mechanistic and spectroscopic investigations led to the discovery of a new protocol for catalytic hydroamidation reactions that draws on easily available ruthenium trichloride trihydrate (RuCl₃·3H₂O) as the catalyst precursor instead of the previously employed, expensive bis(2-methylallyl)(1,5- cyclooctadiene) ruthenium(II). This practical and easy-to-use protocol dramatically improves the synthetic applicability of Ru-catalyzed hydroamidations. The catalyst, generated in situ from ruthenium(III) chloride hydrate, tri-n-butylphosphine, 4-(dimethylamino)-pyridine and potassium carbonate, effectively promotes the addition of secondary amides, lactams and carbamates to terminal alkynes under formation of (E)-anti-Markovnikov enamides. The scope of the new protocol is demonstrated by the synthesis of 24 functionalized enamide derivatives, among them valuable intermediates for organic synthesis.

Full text of DOI:10.1002/adsc.200800508

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DOI: 10.1002/adsc.200800508
A Practical and Effective Ruthenium Trichloride-Based Protocol
for the Regio- and Stereoselective Catalytic Hydroamidation of
Terminal Alkynes
Lukas J. Gooßen,a,* Matthias Arndt,a Mathieu Blanchot,a Felix Rudolphi,a
Fabian Menges,a and Gereon Niedner-Schatteburga,*
a
Fachbereich Chemie, Technische Universitꢀt Kaiserslautern, Erwin-Schrçdinger-Straße, 67663 Kaiserslautern, Germany
Fax : (+49)-631-3921; phone: (+49)-631-205-2046; e-mail: goossen@chemie.uni-kl.degns@chemie.uni-kl.de
Received: August 14, 2008; Published online: November 19, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800508.
Abstract: A rational catalyst development based on
mechanistic and spectroscopic investigations led to
the discovery of a new protocol for catalytic hydro-
amidation reactions that draws on easily available
ruthenium trichloride trihydrate (RuCl3·3H2O) as
the catalyst precursor instead of the previously em-
ployed, expensive bis(2-methylallyl)(1,5-cycloocta-
diene)ruthenium(II). This practical and easy-to-use
protocol dramatically improves the synthetic applic-
ability of Ru-catalyzed hydroamidations. The cata-
reochemistry is controlled by the ligands and either
auxiliary bases or Lewis acids (Scheme 1). They
promise to be valuable alternatives to traditional syn-
Scheme 1. Ru-catalyzed addition of amides to alkynes.
lyst, generated in situ from rutheniumACTHUNRTGNEUNG(III) chloride
hydrate, tri-n-butylphosphine, 4-(dimethylamino)-
pyridine and potassium carbonate, effectively pro-
motes the addition of secondary amides, lactams
and carbamates to terminal alkynes under forma-
tion of (E)-anti-Markovnikov enamides. The scope
of the new protocol is demonstrated by the synthe-
sis of 24 functionalized enamide derivatives, among
them valuable intermediates for organic synthesis.
theses, for example, from carbonyl compounds and
amides[6] or from hydroxylamines and carboxylic an-
hydrides,[7] that usually require harsh conditions and
give (E/Z)-mixtures, and to metal-catalyzed coupling
reactions of amides with vinyl halides, pseudohalides[8]
or ethers,[9] which suffer from limited substrate availa-
bility.
However, practical applications of this and other
Ru-catalyzed additions have so far been hampered by
the prohibitive price of Ru(II) complexes stabilized
with labile ligands, for example, tris(acetonitrile)pen-
tamethylcyclopentadienylruthenium(II) hexafluoro-
phosphate (154 E/mmol), acetonitrilebis(2-diphenyl-
phosphino-6-tert-butylpyridine)-cyclopentadienylru-
Keywords: addition reactions; enamides; homoge-
neous catalysis; hydroamidation; ruthenium
In recent years, the addition of nucleophiles across thenium(II) hexafluorophosphate (425 E/mmol), or
carbon-carbon triple bonds has evolved to become a bis-(2-methallyl)-cycloocta-1,5-diene-ruthenium(II)
versatile tool, for example, for the atom-economic [(cod)RuACHTUNGTRENNUNG
synthesis of enol esters,[1] aldehydes,[2] (en)amines,[3] generating the catalytically active species.[10] The syn-
and imines,[3a,4] as well as enamides and their deriva- thetic utility of this type of addition reaction would
tives.[5] Our own contribution to this field was the de- thus vastly be improved if the catalyst could instead
velopment of effective Ru-catalysts that, for the first be generated from easily available RuACTHNUTRGNE(NUG III) salts such
time, allowed the addition of various amide deriva- as RuCl3·3H2O (5 E/mmol). However, the complexity
tives, such as amides, imides, carbamates, lactams, and of this replacement of the Ru precursor becomes ap-
ureas, to terminal alkynes.[5a–c] These hydroamidations parent when considering the necessity of selectively
are highly anti-Markovnikov-selective, while their ste- reducing RuACTHNURGTNE(UNG III) to Ru(II) during catalyst preforma-
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Scheme 2. Proposed hydroamidation mechanism starting from (cod)RuACHTNUTRGNEG(UN met)2, and from RuCl3·3H2O.
tion, and of scavenging the strongly coordinating of complex d. The amide anion then attacks the coor-
halide ions. dinated alkyne, and the enamide product is finally re-
In the original hydroamidation protocol, the cata- leased from the intermediate e by protonolysis, thus
lyst is generated from (cod)Ru(met)2 (a), tri-n-butyl- regenerating the original catalytic species c.
phosphine, 4-(dimethylamino)pyridine (DMAP), and Apparently, none of the original ligands of the elab-
AHCTUNGTRENNUNG
the amide substrate (Scheme 2, left). In the preforma- orate Ru precursor a actually remain bound to the
tion steps, the 1,5-cyclooctadiene (COD) ligand is dis- metal center, suggesting that simple ruthenium salts
placed by the phosphine and/or DMAP ligands giving may also be utilized as precursors. In our search for a
rise to intermediate b, as indicated by the characteris- protocol that would allow the selective reduction of
tic signals for free, unaltered COD and Ru-coordinat- ruthenium chloride (f) to a Ru(II) species while at
ed PACHTUNGTRENNUNG
(n-Bu3) in GC-MS/NMR spectra.[5c,11] Moreover, the same time removing the chloride ions, which can
the detection of isobutene suggests that the methallyl be expected to compete with the substrates for coor-
À
ligands are protonated off by the N H acidic amides, dination sites at the ruthenium, we came across a
thus leading to a Ru(II) amide complex c. The alter- publication by Kçlle et al.[12] They describe the syn-
native formation of a Ru(0) species appears less thesis of di-m-methoxo-bis[(h5-pentamethylcyclopenta-
likely, as no 2,5-dimethylhexadienes were detected, dienyl)diruthenium(II)
that would have been indicative of a reductive dimeri- pentamethylcyclopentadienyl)chlororutheniumACHTUNGTRENNUNG
from
di-m-chloro-bis[(h5-
(III)]
zation of the methallyl ligands. An ESI-mass spectrum [(Cp*RuCl2)2] using MeOH as reductant and the mild
taken at this stage is dominated by two signals, which base K2CO3 for the generation of the methoxide li-
on the basis of their mass and isotope pattern can be gands as well as for precipitation of the chloride as
attributed to {Ru[P
{Ru[P(n-Bu)3]3A
(C4H6NO)}+ fragments. This again sup-
ports our proposed catalytic cycle that starts from would be successful also for the in situ generation of
[P(n-Bu3)]nA(DMAP)mRu(II) amide complex (c) (see an effective hydroamidation catalyst (Scheme 2,
Figure 1). Initially, the alkyne adds to the Ru center, right), we treated a suspension of RuCl3·3H2O in tol-
possibly displacing one of the ligands under formation uene with K2CO3, methanol, P(n-Bu)3, and DMAP,
(DMAP)}+ and KCl.
ACHTUGNERTN(UNGN n-Bu)3]2ACHTNURTGEG(NNUN C4H6NO)ACHTNUGTRENNGUN
A
N
In order to investigate whether a related strategy
A
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
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A Practical and Effective Ruthenium Trichloride-Based Protocol
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Figure 1. ESI-MS of the catalyst systems based on a) RuCl3 and b) (cod)RuACTHUNRGTNEUNG(met)2.
and added pyrrolidin-2-one (1a) and 1-hexyne (2a) as in acetone followed by evaporation (entry 3).[13] The
typical hydroamidation substrates (Table 1). We were use of (cod)RuCl2 gave comparable results but of-
pleased to find that after heating the reaction mixture fered no advantage (entry 4). Systematic investiga-
to 1008C overnight, the desired product (E)-N-(hex- tions revealed that a base, for example, potassium car-
1-enyl)pyrrolidin-2-one (3aa) had formed in high (E/ bonate or hydroxide, is essential, whereas the alcohol
Z)-selectivity and reasonable but varying yields can be replaced by water (entries 5–9). This goes
(entry 2). The best results obtained with this protocol along with reports in the literature that phosphines
became reproducible when using amorphous RuCl3 themselves can act as reducing agents for transition
generated by dissolution of commercial RuCl3·3H2O metals, a process assisted by water.[14]
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Table 1. Optimization of the catalyst and conditions.[a]
signals for potassium adducts and, for example, chlo-
ride-bridged polynuclear ruthenium species.[15]
We next tested the generality of the new protocol
by applying it to the synthesis of enamide derivatives
from various N-nucleophiles and alkynes. As can be
seen from Table 2, linear and branched aliphatic as
well as aromatic terminal alkynes bearing a range of
functional groups were smoothly and selectively con-
verted with pyrrolidin-2-one in yields that were some-
times even in excess of those obtained with the first-
generation catalyst. Moreover, various N-nucleophiles
could be added to 1-hexyne, including amides, lac-
tams, bislactams, oxazolidinones, and even thioamide
Entry Ru precursor Additive Base
Yields Ratio
[%]
3aa/4aa
1
G
E
–
–
>99
19:1
2
MeOH K2CO3 30–99 5–25:1
3
18:1
24:1
3:2
4
ACHTUNGTRENNUNG
5
6
7
–
7
RuCl3·3H2O[b]
–
K2CO3 95
14:1
23:1
24:1
31:1
31:1
25:1
22:1
substrates that with (cod)RuACHTNUGTRENUNG(met)2 required a custom-
ized set of ligand and additive.[16] The yields and selec-
tivities were usually high, but for acyclic amides do
not quite reach those of the original protocol, which
we attribute to the competition of remaining halide
ions for coordination sites at the ruthenium giving
rise to less active Ru species (Scheme 2, X=Cl). The
protocol could easily be scaled up to gram quantities
RuCl3·3H2O[b] EtOH
RuCl3·3H2O[b] H2O
RuCl3·3H2O[b] H2O
K2CO3 >99
K2CO3 >99
K2CO3 >99
K2CO3 94
9
10[c]
11[d] RuCl3·3H2O[b] H2O
12[e] RuCl3·3H2O[b] H2O
K2CO3 >99
13[f]
RuCl3·3H2O[b] MeOH K2CO3 >99
[a]
Reaction
conditions:
1.00 mmol
pyrrolidin-2-one,
2.00 mmol 1-hexyne, 2 mol% Ru precursor, 6 mol% without any losses in yield or selectivity.
PACHTUNGTRENNUNG(n-Bu)3, 4 mol% DMAP, 10 mol% base, 0.30 mmol ad-
In summary, a practical protocol for hydroamida-
tion reactions has been discovered in which the cata-
lyst is generated in situ from inexpensive ruthenium-
ditive, 3 mL toluene, 1008C, 15 h; yields and selectivities
determined by GC using n-tetradecane as internal stan-
dard.
AHCTUNGTREG(NNUN III) chloride hydrate, tri-n-butylphosphine or its
[b]
The catalyst was injected as
a stock solution of
HBF4 adduct, 4-(dimethylamino)pyridine and potassi-
um carbonate. The catalyst system effectively pro-
motes the addition of secondary amides, thioamides,
lactams and carbamates to terminal alkynes under
formation of (E)-anti-Markovnikov enamides in
RuCl3·3H2O (0.02 mmol) in acetone (1 mL) via syringe.
The solvent was removed under vacuum before any
liquid compound was added.
At 808C.
At 708C.
[c]
[d]
[e]
[f]
1 mol% RuCl3·3H2O, 3 mol% PACTHUNTRGNEU(GN n-Bu)3, 2 mol% DMAP. yields that often match or even exceed those of the
À
[HPACHTUNGTRENNUNG CAHTUNGTERN(NUGN n-Bu)3
(n-Bu)3]+ BF4 instead of P
costly first-generation catalyst, thus greatly extending
the synthetic utility of hydroamidation reactions.
At a temperature of 808C, an optimal balance be-
Experimental Section
tween reaction rate and selectivity was achieved (en-
tries 9–11), leading to near quantitative yields and (E/
Z)-selectivities in excess of 30:1 with a catalyst load-
ing of 2 mol%. Similar results were obtained with 1
mol% of RuCl3·3H2O (entry 12), and when replacing
General Methods
Reactions were performed in oven-dried glassware under a
nitrogen atmosphere containing a Teflon-coated stirrer bar
and dry septum, unless otherwise specified. Solvents were
purified by standard procedures prior to use. All reactions
were monitored by GC using n-tetradecane as an internal
standard. Response factors of the products with regard to n-
tetradecane were obtained experimentally by analyzing
the air-sensitive, liquid PACHTNUTRGNENG(U n-Bu)3 by its tetrafluorobo-
rate salt, which is air- and water-stable, and advanta-
geous especially for large-scale applications
(entry 13).
The performance of this simple system in the known quantities of the substances. GC analyses were car-
ried out using an HP-5 capillary column (Phenyl Methyl Si-
loxane 30 mꢂ320ꢂ0.25, 100/2.3–30–300/3) and a time pro-
gram beginning with 2 min at 608C followed by 308CminÀ1
ramp to 3008C, then 3 min at this temperature. Column
chromatography was performed using a Combi Flash Com-
panion-Chromatography-System (Isco-Systems) and Redi-
model reaction matches that of the expensive
(cod)Ru(met)2-derived catalyst, which supports our
hypothesis that the same type of catalytically active
Ru(II) species is generated with either method
(Scheme 2). Moreover, ESI-MS measurements of a
sample taken from a toluene solution of RuCl3·3H2O,
ACHTUNGTRENNUNG
AHCTUNGTREGSNNUN ep packed columns (12 g). NMR spectra were obtained on
PACHTUNGTRENNUNG
Bruker DPX 400 or on Bruker Avance 600 systems using
CDCl3 or toluene-d8 as solvent, with proton, carbon and
phosphorus resonances at 400/600 MHz, 101/151 MHz and
A
N
ACHTUNGTRENNUNG
{Ru[PACHTUNGTRENNUNG(n-Bu)3]3ACHTUNGTRENNUNG
(C4H6NO)}+, but also contains small 162/243 MHz, respectively. Mass spectral data were acquired
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A Practical and Effective Ruthenium Trichloride-Based Protocol
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Table 2. Substrate scope of the RuCl3-catalyzed hydroamidation.
Product
Yield [%]
Product
Yield [%]
Product
Yield [%]
Product
Yield [%]
(ratio 3/4)
(ratio 3/4)
(ratio 3/4)
(ratio 3/4)
99 (32:1)
99 (40:1)[b]
99 (33:1)
97 (8:1)[b]
96 (25:1)[b]
96 (40:1)[b]
97 (22:1)[b]
99 (24:1)
35
90 (2:1)[b]
30 (40:1)
91 (40:1)
35 (3:1)[b]
99 (40:1)
AHCTUNGTERG(NNUN 1:1)
71 (40:1)[c]
88 (30:1)
10 (2.4:1)[b]
49 (40:1)[b]
20 (40:1)[b]
94 (21:1)
94 (22:1)
80 (3:1)[b]
93 (40:1)[b]
20 (40:1)[b]
[a]
Reaction conditions: 1.00 mmol N-nucleophile (1a–p), 2.00 mmol alkyne (2a–i), 3 mol% RuCl3·3H2O, 9 mol% PACHTNUGTRENUNG(n-Bu)3, 9
mol% DMAP, 15 mol% K2CO3, 0.40 mmol H2O, 3 mL toluene, 15 h, 1008C, isolated yields, selectivities determined by
GC.
[b]
[c]
1
Selectivities determined by H NMR.
4.00 mmol alkyne, selectivity determined by H NMR.
1
on a GC-MS Saturn 2100 T (Varian). Electrospray ioniza-
and data analysis was performed using Bruker Data Analy-
sis 3.4 software.
tion mass spectrometry (ESI-MS) was performed with a
Bruker Esquire 3000plus ion trap instrument. The ion
source was used in positive electrospray ionization mode.
Scan speed was 1650 m/z/s in maximum resolution scan
mode (0.3 FWHM/m/z), scan range was 50 to 1500 m/z. All
spectra were accumulated for at least five minutes. Sample
solutions in toluene at concentrations of 0.007M were fil-
tered through a PVDF filter (0.45 mm–13 mm) and continu-
ously infused into the ESI chamber at a flow rate of
4 mLminÀ1 using a syringe pump. Nitrogen was used as
drying gas with flow rate of 3.0 LminÀ1 at 3008C. The solu-
tions were sprayed at a nebulizer pressure of 4 psi and the
electrospray needle was typically held at 4.5 kV. The instru-
ment was controlled by Bruker Esquire Control 5.3 software
Catalytic Hydroamidation as Exemplified by the
Synthesis of (E)-N-(Hex-1-enyl)pyrrolidin-2-one (3aa)
An oven-dried flask was charged with potassium carbonate
(276.0 mg, 2.00 mmol), 4-(dimethylamino)pyridine (97.7 mg,
0.80 mmol) and a stock solution of rutheniumACTHNURTGNEU(GN III) chloride
hydrate (100.5 mg, 0.40 mmol) in acetone (20.00 mL). The
solvent was removed under vacuum, and after purging the
flask with alternating vacuum and nitrogen cycles, dry tolu-
ene (50.00 mL), water (108 mL, 6.00 mmol), pyrrolidin-2-one
(1a, 1.54 mL, 20.00 mmol), tri-n-butylphosphine (300 mL,
1.20 mmol), and 1-hexyne (2a, 4.63 mL, 40.00 mmol) were
added via syringe. The reaction solution was monitored
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using GC. After full conversion (2 h), it was diluted with
ethyl acetate (250 mL) and aqueous sodium bicarbonate
(2N, 150 mL). The resulting mixture was extracted repeated-
ly with 50 mL portions of ethyl acetate, the combined organ-
ic layers were washed with water and brine, dried over mag-
nesium sulfate, filtered, and the solvent was removed under
vacuum. The residue was pre-adsorbed on a pad of silica gel
(10 g), layered over additional silica gel (20 g), non-polar
impurities, for example, alkyne oligomers, were washed off
with hexane (200 mL) and the product was eluted with an
ethyl acetate/hexane mixture (3:7, 200 mL). The solvent was
removed under vacuum and the residue was purified by
vacuum distillation (1508C/3ꢂ10À2 bar) affording 3aa as a
yellowish oil; yield: 3.30 g (99%). Its spectroscopic data
matched those reported in the literature [CAS: 863709–29–
9].
cealed among the overlapping alkyl signals of tri-n-butyl-
phosphine in the range of d=0.0–2.5 ppm. The 31P NMR
spectrum now solely shows coordinated tri-n-butylphosphine
(d=20.0 ppm).
ESI-MS Studies of the Catalyst Preformation
An oven-dried flask was charged with (cod)RuACHTUNGTRENNUNG(met)2
(6.4 mg, 0.02 mmol) and DMAP (4.9 mg, 0.04 mmol), and
flushed with nitrogen. Subsequently, dry toluene (3.0 mL),
pyrrolidin-2-one (1a, 77 mL, 1.00 mmol), and tri-n-butylphos-
phine (15 mL, 0.06 mmol) were added via syringe. After stir-
ring the resulting solution for 1 h at 1008C, a sample of
0.5 mL was analyzed as described in the general procedure
(C4H6NO)}+ [m/z (%
showing the fragments {Ru[PACHTNUGTRENNUG(n-Bu)3]3ACHTUTGNRENNUGN
relative to peak at 792.4)=786.4 (13), 787.5 (7), 788.4 (6),
789.4 (34), 790.4 (43), 791.4 (55), 792.4 (100), 793.4 (40),
794.4 (58), 795.4 (24), 796.3 (5); calculated: 786.5 (14), 787.5
(6), 788.6 (6), 789.5 (34), 790.5 (46), 791.5 (59), 792.5 (100),
NMR Studies of the Catalyst Preformation
793.5 (39), 794.5 (54), 795.5 (22), 796.5 (5)] and {Ru[P
ACHTUNGTRENNUNG(n-
The in situ formation of the catalyst from (cod)RuACTHNUTRGNEUNG(met)2
Bu)3]2A(C4H6NO)
E
ACHTUNGTRENNUNG
was investigated by a series of 1H and 31P NMR experi-
ments:
712.3)=706.3 (14), 707.3 (5), 708.3 (7), 709.3 (27), 710.4
(36), 711.3 (47), 712.3 (100), 713.3 (27), 714.3 (42), 715.3
(18), 716.2 (7); calculated: 706.4 (14), 707.4 (6), 708.4 (6),
709.4 (34), 710.4 (45), 711.4 (59), 712.4 (100), 713.4 (36),
714.4 (54), 715.4 (20), 716.4 (4)].
An oven-dried flask was charged with potassium carbon-
ate (13.8 mg, 0.10 mmol), and a stock solution containing
rutheniumACTHNUTRGNEUG(N III) chloride hydrate (5.2 mg, 0.02 mmol), 4-(di-
A 5-mm NMR tube was charged with (cod)RuACTHNUGTRENUNG(met)2
(12.8 mg, 0.04 mmol) and DMAP (9.8 mg, 0.08 mmol). The
tube was sealed with a rubber septum and purged with alter-
nating vacuum and nitrogen cycles. Tri-n-butylphosphine
(30 mL, 0.012 mmol) and toluene-d8 (1 mL) were added via
syringe and placed in an ultrasonic bath for 3 min to give a
clear yellow solution.
methylamino)pyridine (4.9 mg, 0.04 mmol), and acetone
(1.0 mL). The acetone was removed under vacuum and the
flask was flushed with nitrogen. Subsequently, dry toluene
(3.0 mL), water (5 mL, 0.30 mmol), pyrrolidin-2-one (1a,
77 mL, 1.00 mmol), and tri-n-butylphosphine (15 mL,
0.06 mmol) were added via syringe. After stirring the result-
ing solution for 1 h at 1008C, a sample of 0.5 mL was ana-
lyzed as described in the general procedure showing the
1
The H NMR spectrum taken at this point, prior to cata-
lyst preformation, shows clear singlets at d=3.47 (2H), 2.80
(2H), 1.69 (6H), 1.53 (2H), and 0.15 (2H) ppm for two
ruthenium-bound methallyl ligands, and multiplets at d=
3.87–3.92, 2.82–2.91, 2.68–2.75, 1.86–1.97 ppm (2H each),
1.55–1.63 and 1.09–1.16 ppm (2H each, overlapping with sig-
nals of the phosphine ligands) for the ruthenium-bound
COD ligand. Doublets at d=8.34 and 6.07 ppm (2H each)
and a singlet at d=2.28 (6H) ppm indicate the presence of
free DMAP ligands. The 31P NMR spectrum at 258C shows
a minor signal at d=20.8 ppm for metal-coordinated tri-n-
butylphosphine and a strong signal at d=À31.1 ppm for un-
coordinated phosphine.
(C4H6NO)}+ [m/z (%)=786.4 (14),
fragments {Ru[PACHTNUTRGENN(UG n-Bu)3]3ACHTUTGNRENNUGN
787.4 (8), 788.4 (7), 789.4 (29), 790.4 (45), 791.4 (58), 792.4
(100), 793.4 (43), 794.4 (52), 795.4 (22), 796.3 (6)] and
(DMAP)}+ [m/z (%)=706.4 (26),
{Ru[PACTHNUGTREN(NNGU n-Bu)3]2ACHTUNRTEGG(NNNU C4H6NO)ACHTNGUTRENNGUN
707.3 (15), 708.4 (14), 709.3 (50), 710.2 (51), 711.3 (74),
712.3 (100), 713.3 (42), 714.3 (63), 715.2 (24), 716.1 (10)].
After heating the above solution to 1008C for 5 min, the
NMR spectra revealed that now, the COD ligand had com-
1
pletely been displaced. In the H NMR spectrum, the signals
Acknowledgements
for coordinated COD ligands have disappeared, and signals
at d=5.43–5.57 (4H) and 2.14–2.24 (8H) ppm indicate free
1,5-cyclooctadiene.
We thank Umicore AG for generous donations of ruthenium
catalysts, the DFG, OPTIMAS and NanoKat for funding, the
DAAD for scholarships for K.S.M.S and M. B., the FCI and
the Studienstiftung des deutschen Volkes for scholarships for
F.R., and S. Ambrus and C. Riehn for support with the ESI-
MS studies.
Due to the ligand exchange, the signals for the methallyl
ligands are shifted to higher field, making an assignment dif-
ficult. Signals for isobutene which would indicate protonoly-
sis or decomposition of the ruthenium complex cannot be
observed. A strong signal for coordinated phosphine at d=
20.8 ppm in the 31P NMR spectrum confirmed that most of
the phosphine was bound to the Ru center at this point in
time.
References
After the addition of pyrrolidin-2-one (1a, 6.2 mL,
0.08 mmol) via syringe, the methyl ligands were protonated
off by the amide, and signals at d=4.60–4.67 and 1.61 ppm
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1
in the H NMR spectrum gave evidence of the formation of
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2.62–2.80 ppm, whereas the other ring protons being con-
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Adv. Synth. Catal. 2008, 350, 2701 – 2707

A Practical and Effective Ruthenium Trichloride-Based Protocol
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since the electrospray process itself is known to en-
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course, solvated RuCl3 is more affected by both pro-
cesses than (cod)Ru
erations the observation of {Ru[P
as a dominating peak and of {Ru[P
(DMAP)} as a well detectable, although minor peak is
of high significance.
ACHTUNGTRENNUNG
A
CHTUNGTRENNUNG
A
CHTUNGTRENNUNG
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