Atom Economic Ruthenium-Catalyzed Synthesis of Bulky β-Oxo Esters

Article abstract of DOI:10.1002/adsc.201500712

Ruthenium complexes with the formulae Ru(CO)₂(PR₃)₂(O₂CPh)₂ [6a-h; R=n-Bu, p-MeO-C₆H₄, p-Me-C₆H₄, Ph, p-Cl-C₆H₄, m-Cl-C₆H₄, p-CF₃-C₆H₄, m,m′-(CF₃)₂C₆H₃] were prepared by treatment of triruthenium dodecacarbonyl [Ru₃(CO)₁₂] with the respective phosphine and benzoic acid or by the conversion of Ru(CO)₃(PR₃)₂ (8e-h) with benzoic acid. During the preparation of 8, ruthenium hydride complexes of type Ru(CO)(PR₃)₃(H)₂ (9g, h) could be isolated as side products. The molecular structures of the newly synthesized complexes in the solid state are discussed. Compounds 6a-h were found to be highly effective catalysts in the addition of carboxylic acids to propargylic alcohols to give valuable β-oxo esters. The catalyst screening revealed a considerably influence of the phosphine′s electronic nature on the resulting activities. The best performances were obtained with complexes 6g and 6h, featuring electron-withdrawing phosphine ligands. Additionally, catalyst 6g is very active in the conversion of sterically demanding substrates, leading to a broad substrate scope. The catalytic preparation of simple as well as challenging substrates succeeds with catalyst 6g in yields that often exceed those of established literature systems. Furthermore, the reactions can be carried out with catalyst loadings down to 0.1mol% and reaction temperatures down to 50 C.

Full text of DOI:10.1002/adsc.201500712

UPDATES
DOI: 10.1002/adsc.201500712
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo
Esters
Janine Jeschke,a Marcus Korb,a Tobias Rüffer,a Christian Gäbler,a
and Heinrich Langa,*
a
Technische Universität Chemnitz, Faculty of Natural Sciences, Institute of Chemistry, Inorganic Chemistry, 09107
Chemnitz, Germany
Fax: (+49)-(0)371-531-21219; phone: (+49)-(0)371-531-21210; e-mail: heinrich.lang@chemie.tu-chemnitz.de
Received: July 31, 2015; Revised: September 8, 2015; Published online: November 25, 2015
Dedicated to Professor Dr. Klaus Banert on the occasion of his 60th birthday.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500712.
Abstract: Ruthenium complexes with the formulae
Ru(CO)2(PR3)2(O2CPh)2 [6a–h; R=n-Bu, p-MeO-
C6H4, p-Me-C6H4, Ph, p-Cl-C6H4, m-Cl-C6H4, p-
CF3-C6H4, m,m’-(CF3)2C6H3] were prepared by
Introduction
Designing effective catalysts for reactions with high
atom economy and high selectivity is still a fundamen-
tal goal for the chemical industry, as it faces rising
costs of waste disposal.[1,2] In this context, ruthenium
catalysts obtain increasing interest because of their
ability to catalyze a variety of selective carbon-carbon
and carbon-heteroatom bond formations.[3,4]
Ruthenium catalysts are known to activate alkynes
towards nucleophilic attack by coordination of the
triple bond to the electrophilic metal center.[5,6] De-
pending on the tautomerization between h2-alkyne
and vinylidene binding modes the ruthenium com-
plexes promote either the Markovnikov addition or
afford the anti-Markovnikov products by nucleophilic
attack at the a-carbon of the vinylidene analogues
(Scheme 1).[7–9]
treatment
of
triruthenium
dodecacarbonyl
[Ru3(CO)12] with the respective phosphine and ben-
zoic acid or by the conversion of Ru(CO)3(PR3)2
(8e–h) with benzoic acid. During the preparation of
8, ruthenium hydride complexes of type
Ru(CO)(PR3)3(H)2 (9g, h) could be isolated as side
products. The molecular structures of the newly
synthesized complexes in the solid state are dis-
cussed. Compounds 6a–h were found to be highly
effective catalysts in the addition of carboxylic acids
to propargylic alcohols to give valuable b-oxo
esters. The catalyst screening revealed a considera-
bly influence of the phosphine’s electronic nature
on the resulting activities. The best performances
were obtained with complexes 6g and 6h, featuring
electron-withdrawing phosphine ligands. Addition-
ally, catalyst 6g is very active in the conversion of
sterically demanding substrates, leading to a broad
substrate scope. The catalytic preparation of simple
as well as challenging substrates succeeds with cata-
lyst 6g in yields that often exceed those of estab-
lished literature systems. Furthermore, the reactions
can be carried out with catalyst loadings down to
0.1 mol% and reaction temperatures down to 508C.
The nucleophilic addition of carboxylic acids to ter-
minal alkynes is an elegant method to produce enol
esters.[10] The addition to propargylic alcohols leads to
b-oxo esters (Scheme 2),[11] which are useful inter-
mediates in the synthesis of natural products and
pharmaceuticals.[12] For example, b-oxo esters can be
Keywords: homogeneous catalysis; phosphines;
propargylic alcohols; ruthenium; solid state struc-
ture
Scheme 1. Tautomerization of alkyne/vinylidene complexes
and their different reactivity towards nucleophilic attack.[7]
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4069

UPDATES
Janine Jeschke et al.
Scheme 2. Formation of b-oxopropyl esters by the Ru-cata-
lyzed addition of carboxylic acids to propargylic alcohols.
easily transformed into the corresponding a-hydroxy
ketones,[13] which are key building blocks in many nat-
ural products.[12b,14] As activated esters they are effi-
cient acylating reagents which give access to amides
and peptides.[15,16] It has been shown that they can
also be used as antibacterial compounds[17] and photo-
labile protecting groups for carboxylic acids.[18] In ad-
dition, they are intermediates in the synthesis of
furanones[19] and imidazoles.[20]
In comparison to other known synthetic methodol-
ogies for the preparation of b-oxo esters, e.g., the
two-step hydration/esterification of propargylic alco-
hols,[21] the carboxylation of a-halo ketones,[18a] the
Scheme 3. Proposed mechanism for the Ru-catalyzed forma-
tion of b-oxopropyl esters.[27–29]
copper-catalyzed insertion of a-diazo ketones into the
[22]
À
O H bond of carboxylic acids, the Wacker oxida-
tion of allyl carboxylates[23] or the oxidation of ke- um(II) complexes containing hydrosoluble phosphine
tones with metal acetate complexes,[24] the direct ligands enable the formation of b-oxo esters in aque-
ruthenium-catalyzed addition is the most straightfor- ous medium.[27]
ward and atom-economical route. Moreover, the reac-
Recently, we could show for the first time that
tion conditions are relatively mild (60 to 1208C) and mononuclear ruthenium compounds of the type
the substrates are simple and commercially avail- [Ru(CO)2(PPh3)2(O2CR)2] (R=CH2OCH3, i-Pr, t-Bu,
able.[25]
2-cyclo-C4H3O, Ph) are efficient catalysts for the addi-
The proposed mechanism for the ruthenium-cata- tion of carboxylic acids to propargylic alcohols, even
lyzed formation of b-oxo esters starts with the nucleo- when challenging substrates were applied.[33] The
philic attack of the carboxylic acid to the h2-alkyne varying carboxylate ligands did not have an influence
ruthenium complex A giving Markovnikov addition. on the productivities, because the carboxylates ex-
To explain the regioselectivity of the nucleophilic change rapidly during the reaction, as it was proven
attack at the C-2 position of the alkyne, the species B by 31P{1H} NMR spectroscopic studies.[33]
and C have been postulated as reactive intermedi-
In continuation of our investigations and since the
ates.[4,16,26] The resulting enol ester D undergoes an in- tautomerization between the h2-alkyne and vinylidene
tramolecular transesterification to the alkenyl deriva- binding mode (Scheme 1) should be affected by elec-
tive E, which after keto-enol tautomerization and pro- trophilicity of the metal fragment,[7–9,34] we explored
tonation releases the b-oxo ester and regenerates the the electronic influence of different phosphine ligands
catalytically active ruthenium species (Scheme 3).[27–29] on the reactivity of the catalytic system. Accordingly,
The first catalytic system which was able to gener- we synthesized a series of novel mononuclear Ru(II)
ate b-oxo esters was described by Mitsudo and Wata- complexes of type [Ru(CO)2(PR3)2(O2CPh)2] [R=n-
nabe.[30] They employed a mixture composed of Bu, p-MeO-C6H4, p-Me-C6H4, Ph, p-Cl-C6H4, m-Cl-
bis(h5-cyclooctadienyl)ruthenium,
P(n-Bu)3
and C6H4, p-CF3-C6H4, m,m’-(CF3)2C6H3] with modified
maleic anhydride. To date, the best results in terms phosphine ligands. These ruthenium complexes were
of productivity and selectivity have been achieved successfully applied in the catalytic formation of b-
with
mononuclear
arene-Ru(II)
derivatives oxo esters under mild reaction conditions. Further-
[Ru(h6-arene)(PR3)Cl2] [arene=p-cymene, C6H6, more, experiments to better understand the mecha-
C6Me6;
PR3 =PPh3,
PMe3,
phosphoramidite, nism of the reaction, like a correlation of the Ham-
ꢀ
P(cyclo-C4H3O)2(C CFc)], the mononuclear bis(al- mett value and the reaction rate for a series of para-
lyl)ruthenium(IV)
C10H16)(PPh3)Cl2]
complex
the
trans-[Ru(h3:h3- substituted benzoic acids, were performed.
and
dimeric
complex
[Ru2(CO)4(PPh3)2(m2-O2CH)2].[11,27–29,31,32] In addition,
Cadierno and co-workers have shown that rutheni-
4070
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 4069 – 4081

UPDATES
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo Esters
Results and Discussion
m,m’-(CF3)2C6H3].
The
isostructural
complex
Ru(CO)(PPh3)3(H)2 is known since 1968[37] and has
become an important and widely used catalyst espe-
cially in hydrogen transfer reactions.[38]
Synthesis and Characterization of Novel Ruthenium-
Carboxylate Complexes
The ruthenium complexes 8e–h were subsequently
The ruthenium complexes [Ru(CO)2(PR3)2(O2CPh)2] converted with benzoic acid to novel ruthenium car-
with basic phosphine ligands (6a, R=n-Bu; 6b, R=p- boxylates [Ru(CO)2(PR3)2(O2CPh)2] [6e, R=p-Cl-
MeO-C6H4; 6c, R=p-Me-C6H4; 6d, R=Ph) were pre- C6H4; 6f, R=m-Cl-C6H4-Cl; 6g, R=p-CF3-C6H4; 6h,
pared starting from Ru3(CO)12 (4) by a single step R=m,m’-(CF3)2C6H3] (Scheme 6).[39] As solvent for
conversion with the respective phosphine 5 and ben- this conversion 4-methylpentan-2-one was chosen, as
zoic acid (2a) analogously to a procedure described it prevents the formation of dinuclear ruthenium side
by Bianchi[35] (Scheme 4).
products.[33] For complexes 6b–d a preparation meth-
odology starting from Ru(CO)3(PR3)2 (8b–d) is also
possible.
Scheme 4. Synthesis of ruthenium complexes 6a–d.
For ruthenium complexes 6e–h featuring electron-
withdrawing phosphine ligands the above described
synthesis procedure led, however, to poor yields and
purities of the obtained products. Therefore, we chose
another preparation strategy using Ru(CO)3(PR3)2
Scheme 6. Synthesis of ruthenium complexes 6e–h. (i) 4-
Methylpentan-2-one, 1008C, 1 h.
The identity of all compounds was confirmed by el-
[8e, R=p-Cl-C6H4; 8 f, R=m-Cl-C6H4; 8g, R=p-CF3- emental analysis, IR and NMR (1H, 13C{1H}, 31P{1H})
C6H4; 8h, R=m,m’-(CF3)2C6H3] as starting material. spectroscopy and ESI mass spectrometry (see the
Complexes 8e–h could be obtained by slightly modi- Supporting Information). In addition, the structures
fied literature procedures.[36] To a boiling solution of of 6a–c, 6e–h, 8e–h and 9g in the solid state were de-
RuCl3·xH2O (7), the phosphine 5 and KOH dissolved termined by single-crystal X-ray structure analysis.
in 2-methoxyethanol an aqueous formaldehyde solu-
The 31P{1H} NMR spectra of 6a–h and 8b–h each
tion was added (Scheme 5). The less basic the phos- exhibit one singlet for the phosphine ligands in
phine, the longer the solution had to be refluxed (2 to a range from 17.6 to 35.9 ppm for 6a–h and from 49.8
18 h) after which time the product precipitated as to 63.5 ppm for 8b–h (Table 1). When compared to
yellow microcrystals. For the success of this reaction, the free phosphines 5a–h, all resonance signals of the
particularly for the preparation of 8g and 8h, an ade- as-prepared ruthenium complexes are shifted down-
quate amount of solvent is essential to avoid precipi- field, indicating the coordination to the transition
tation of sparingly soluble intermediates, which then metal.[40]
may fail to react further. As such intermediates we
could isolate ruthenium hydride complexes of type
Ru(CO)(PR3)3(H)2 [9g, R=p-CF3-C6H4; 9h, R=
Table 1. Comparison of 31P{1H} NMR d values of complexes
6a–h and 8b–h with free phosphines 5a–h.
[a]
[a]
d PR3 [ppm]
d PR3[a] [ppm]
d free PR3 [ppm]
6a
6b
6c
6d
6e
6f
6g
6h
17.6
28.3
29.8
31.2
30.7
32.4
32.8
35.9[b]
5a
5b
5c
5d
5e
5f
5g
5h
À30.9
À10.1
À7.9
À5.4
À8.4
À4.5
À6.0
À4.3
8b
8c
8d
8e
8f
8g
8h
49.8
52.5
55.4
54.4
58.4
57.6
63.5[b]
[a]
[b]
Scheme 5. Synthesis of ruthenium complexes 8e–h and 9g, h.
(i) 2-Methoxyethanol, HCHO, KOH, DT, 2–18 h.
Solvent: CDCl3.
Solvent: acetone-d6.
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
4071

UPDATES
Janine Jeschke et al.
1
The H and 13C{1H} NMR spectra of 6a–h and 8b–h
Table 2. IR stretching frequencies of carbonyl and carboxyl-
ate groups of complexes 6a–h.
are in accordance with the proposed structures. Some
of the signals in the 13C{1H} NMR spectra are split
into triplets. This is a common phenomenon for com-
plexes containing trans-phosphine ligands, which was
observed for this kind of complexes before.[33] Fur-
thermore, this finding is confirmed by calculations of
Metzinger[41] and Harris.[42]
[a]
˜
˜
Complex
nCO [cmÀ1]
DnCO [cmÀ1]
2
6a
6b
6c
6d
6e
6f
6g
6h
2036 (vs), 1970 (vs)
2030 (s), 1966 (s)
2045 (s), 1983 (s)
2047 (vs), 1986 (vs)
2035 (vs), 1972 (vs)
2044 (vs), 1982 (vs)
2051 (s), 1991 (s)
2059 (m), 2007 (m)
264
254
252
270
269
275
284
277
1
The H NMR spectrum of complex 9g exhibits hy-
dride signals ranging from À8.8 to À7.1 ppm with
a characteristic splitting pattern of a triplet of dou-
blets of doublets (tdd) for the hydride cis to Peq and
a doublet of triplets of doublets (dtd) for the hydride
trans to Peq (Figure 1a). The 31P{1H} NMR spectrum
of 9g shows two signals of which the equatorial phos-
[a]
˜
˜
˜
DnCO =DnasymÀDnsym
.
2
phine Peq reveals a triplet at 46.1 ppm and the axial from 252 to 284 cmÀ1 indicate a monodentate coordi-
phosphine groups Pax a doublet at 57.6 ppm (Fig- nation of the carboxylate groups (Table 2), which was
ure 1b).
confirmed by single-crystal X-ray structure determi-
nation (see below).
The ruthenium carboxylates 6a–c, 6e–h, the tricar-
bonyl containing 8b, e, g and ruthenium hydrides
9g, h were characterized by single-crystal X-ray dif-
fraction analysis. One example of each type of ruthe-
nium complexes is shown in Figure 2, Figure 3 and
Figure 4, respectively. Remaining structures, the ex-
planation of the crystal growth as well as further de-
tails pertaining to the crystal and structure refinement
data are summarized in the Supporting Information.
The title compounds crystallize in the triclinic space
group P-1 (6f, g, 8e, g), in the monoclinic space
Figure 1. a) 1H NMR spectrum of 9g in CDCl3 (hydride
region); b) 31P{1H} NMR spectrum of 9g in CDCl3.
The IR spectra of ruthenium complexes 6a–h distin-
guish themselves by two intensive absorptions for the
stretching vibrations of the terminal carbonyl groups
between 1966 and 2059 cmÀ1 and by the characteristic
˜
˜
bands for the asymmetric (nasym) and symmetric (nsym
)
carboxylate stretching vibrations. From the number of
the CO vibrations one can conclude that the carbonyl
groups have to adopt a cis-arrangement in the octahe-
dral coordination sphere of the Ru(II) ion, as for
a trans isomer only one strong carbonyl stretching is
expected.[39b] The increasing frequency of the carbonyl
stretching vibrations for complexes 6a–h as well as
8b–h indicates a decreased back-bonding in electron-
poor complexes (Table 2). Furthermore, the separa-
À
˜
˜
˜
˜
tion DnCO (DnCO =nasymÀnsym) between the C O
2
2
Figure 2. ORTEP diagram (50% probability level) of the
molecular structure of 6g with the selected atom numbering
scheme. Hydrogen atoms and packing solvent (CH2Cl2)
stretching frequencies can be used to estimate the
nature of carboxylate coordination as described by
Deacon and Phillips.[43] The large values of Dn ranging have been omitted for clarity.
˜
4072
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 4069 – 4081

UPDATES
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo Esters
groups C2/c (6a, c), P21/c (6b, 9g), P21/n (6e, 8b, 9h)
and P21/a (6h) with one crystallographically independ-
ent molecule in the asymmetric unit, except for 6h
with two and 6a with one half of the compound and
a mirror plane through the Ru atom. Some crystals
contain packing solvent (see the Supporting Informa-
tion). Most of the CF3 substituents and disordered
phenyl rings have been refined using rigid models
(AFIX, DFIX and DANG instructions).
The octahedral ruthenium carboxylates 6a–c and
6e–h (Figure 2, Supporting Information, Figures S1–
S6) consist of two axial trans-positioned phosphines
and two cis-carbonyl and benzoate ligands in the
equatorial plane, with the phosphines bent towards
À
À
the carboxylates with P Ru P angles of 166.75(4)–
175.47(3)8. The carbonyl oxygens of the carboxylates
are directed to the carbonyls avoiding electronic inter-
À
À
actions. Thus, the steric demand affects the O Ru C
angle, which is increased to 94.51(6)–96.80(8)8, where-
as the O Ru O [79.06(8)–82.74(10)8] and C Ru C
[84.45(18)–88.96(10)8] angles are decreased. Within
the carboxylate moieties a clear distinction between
À
À
À
À
À
a C O single bond, with 1.287(3)–1.303(6) Š, bonded
to the Ru atom, and a C=O double bond of 1.225(6)–
1.235(3) Š is possible, which verifies the results of the
IR measurements (Table 2).
Furthermore, the carboxylate plane is almost copla-
nar with the phenyl ring [5.7(2)–23.2(4)8] and the cen-
tral C2O2Ru plane [19.7(3)–32.82(11)8].[44] The tor-
sions of the carbonyl atoms of the carboxylates in
each complex are always directed anti, above and
below the central plane.
Figure 3. ORTEP diagram (30% probability level) of the
molecular structure of 8g with the selected atom numbering
scheme. Hydrogen atoms, disordered parts and packing sol-
vent (CH2Cl2) have been omitted for clarity.
Tricarbonyl containing compounds 8b, 8e and 8g more, an influence of the phosphines is also not pres-
À
(Figure 3, Supporting Information, Figures S7 and S8) ent for the Ru P bonds, which are comparable for
exhibit a trigonal bipyramidal coordination environ- the carboxylates 6 and 8b [2.3496(13)–2.4297(6) Š].
ment with both phosphines in the axial position. The However, the tricarbonyl compounds 8e, g exhibit sig-
À
À
higher symmetry results in more linear P Ru P nificantly shorter bond lengths of 2.3264(16)–
angles [174.46(2)–178.95(7)8] compared to the carbox- 2.3311(9) Š, due to their electron withdrawing para
ylates 6. Dihydrido complexes 9g, h (Figure 4, Sup- substituents. In the dihydrido complexes 9g, h a differ-
À
porting Information, Figure S9) exhibit a strong dis- entiation between the axial phosphines, whose Ru P
torted octahedral coordination environment, bearing bonds are shortened to 2.304(3)–2.3199(15) Š and
two phosphine ligands in the axial, and one in the those in the equatorial plane with longer distances of
equatorial position with the remaining carbonyl 2.366(3)–2.3698(16) Š is possible (Supporting Infor-
ligand and both hydrogens arranged cis towards each mation, Table S12).
other. The steric demand of the equatorial phosphine
diminishes the P Ru P angle to 143.81(11) (9g) and 8b remains coplanar between 0.1(4) and 15.1(4)8.
148.87(6)8 (9h) bending towards both hydrogens, and
The torsion of the p-methoxy substituents in 6b and
À
À
thus, increases the angles between the phosphines in
equatorial and axial position to 99.54(5)–109.57(10)8. Catalytic Experiments
À
The positions of the hydrogen atoms and their Ru H
distances were refined based on residual electron den- As in our previous catalytic investigations we chose
sity in 9h [1.63(6) and 1.55(5) Š] or fixed to 1.80(2) Š the conversion of benzoic acid and propargylic alco-
for 9g, due to strongly deviating values for known hol in toluene as model reaction.[33] The reactions
crystal structures.[45]
were performed under relatively mild conditions and
ꢀ
The C O bond of the carbonyls is neither affected no special precautions against air or moisture in the
by the electronically different phosphines, nor by dif- handling of the complexes were needed. In a typical
ferent substitution patterns at the Ru atom. Further- experiment, benzoic acid (1.0 mmol), propargylic
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
4073

UPDATES
Janine Jeschke et al.
Table 3. Dependency of the productivity on the applied cata-
lyst and temperature in the formation of 2-oxopropyl ben-
zoate.[a]
Yield[b] [%]
Entry
Catalyst
508C
558C
608C
658C
708C
1
2
3
4
5
6
7
8
6a
6b
6c
6d
6e
6f
6g
6h
2
6
15
85
64
36
66
44
96
92
47
98
98
89
96
96
98
98
89
98
98
97
98
98
98
98
15
14
10
12
10
30
32
38
31
23
37
29
53
81
[a]
Reaction conditions: benzoic acid (1.0 mmol), propargylic
alcohol (2.0 mmol), catalyst 6 (0.01 mmol), acenaphthene
(0.5 mmol), 24 h, toluene (1 mL).
[b]
The yields were determined by 1H NMR spectroscopy
applying acenaphthene as internal standard.
Figure 4. ORTEP diagram (50% probability level) of the
molecular structure of 9g with the selected atom numbering
scheme. Aromatic hydrogen atoms, disordered parts and
packing solvent (3 toluene) have been omitted for clarity.
screening of ruthenium complexes 6a–h with varying
phosphine ligands revealed a considerably influence
of the phosphine’s nature on the productivity. At
608C the best yields of more than 90% were obtained
with complexes 6g, h, which possess the most elec-
alcohol (2.0 mmol), the catalyst 6 (0.01 mmol) and tron-withdrawing phosphine ligands. Conversely, only
acenaphthene (0.5 mmol) as internal standard were 15% was reached with the most basic P(n-Bu)3-substi-
dissolved in toluene (1 mL) and reacted for 24 h at tuted complex 6a. This finding can be explained with
ꢀ
608C. The products have all been characterized spec- a facilitated coordination of an electron-rich C C
troscopically, and the efficiencies of the reactions triple bond to the electrophilic ruthenium ion, which
1
have been determined by H NMR spectroscopy (for probably is the first and rate-determining step of the
optimization studies and reaction profiles) or by isola- catalytic cycle. Additionally, electron-withdrawing li-
tion (substrate screening).
gands at the ruthenium do not favor the tautomeriza-
It was already shown that the carboxylates bound tion of the h2-alkyne to a vinylidene complex, which
to the ruthenium in 6 do not influence the productivi- would lead to side reactions like anti-Markovnikov
ties of the reactions, because they exchange rapidly in addition.[10k] However, the substituted triarylphos-
solution for the carboxylic acids applied during the re- phine complexes 6b, c with electron-donating triaryl-
action.[33] For this reason we decided just to prepare phosphine ligands give better yields than the isostruc-
and apply the respective benzoate complexes of 6, as tural PPh3-substituted complex 6d. A possible explan-
in our model reaction and most other reactions ben- ation for the increased yields can be found in a facili-
zoic acid was converted.
tated generation of the catalytic active species, which
Table 3 shows the screening of ruthenium com- partly compensates electronic drawbacks during the
plexes 6a–h in the addition of benzoic acid to propar- actual catalytic cycle.
gylic alcohol to give 2-oxopropyl benzoate at varying
In contrast to our previous reported catalytic reac-
temperatures. In general, it can be seen that the work- tions with less active PPh3-substituted ruthenium com-
ing temperature plays a crucial role. A decrease of plexes,[33] we waived the addition of Na2CO3, as no
the temperature by only 58C can lead to a productivity enhancement was detected for the application with
drop by half or even more. All catalysts, except for more active catalysts 6g, h.
6a, reached nearly quantitative yields at 708C, where-
Besides the productivity, the catalytic activity was
as the conversion at 508C is for all tested complexes also studied. Therefore, the addition of benzoic acid
less than one third. The best conditions to compare to propargylic alcohol was followed over time for se-
the performances of the catalysts were found at 608C lected catalysts. The yield-time plots are depicted in
due to the wide range of the obtained yields. The Figure 5. The overall productivity is mainly deter-
4074
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 4069 – 4081

UPDATES
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo Esters
Table 4. Dependency of the productivity on the ruthenium
loading in 2-oxopropyl benzoate formation.[a]
Yield[b] [%]
Catalyst (mol%)
0.1
0.25
0.5
0.75
1.0
6g
6h
34
45
60
86
82
91
88
91
96
92
[a]
Reaction conditions: benzoic acid (1.0 mmol), propargylic
alcohol (2.0 mmol), acenaphthene (0.5 mmol), 24 h at
608C in toluene (1 mL).
[b]
The yields were determined by 1H NMR spectroscopy
applying acenaphthene as internal standard.
Figure 5. Kinetic investigation for catalysts 6b, d, e, g, h, 10
and 11 in the reaction of benzoic acid with propargylic alco-
hol to give 2-oxopropyl benzoate (1.0 mol% based on [Ru],
608C) followed over time by H NMR spectroscopy; for re-
action conditions see Table 3.
cohols were converted with catalysts 6g, h and litera-
ture known 10 to explore their substrate generality
(Table 5). Whereas the productivity of the catalysts is
comparable, when applying the simplest propargylic
alcohol 1a, significant differences in the obtained
1
mined by the length of activation time at the begin- yields were observed when sterically more demanding
ning of the conversion, whereas the activity of investi- substrates like 2-methyl-3-butyn-2-ol (1g) or 1-ethy-
gated complexes 6b, d, e, g, h is well comparable after nylcyclohexanol (1l) were reacted with benzoic acid
the generation of the catalytic active species. Further- at 608C. The performance of literature known catalyst
more, we did compare the activity of our complexes 10 is strongly dependent on the steric hindrance of
with literature known catalysts. As typical examples
we chose the mononuclear Ru(p-cymene)PPh3Cl2
(10)[11] and the dinuclear Ru2(CO)4(PPh3)2(O2CH)2
Table 5. Screening of varying propargylic alcohols in the for-
(11)[31] species. When equal ruthenium loadings are
mation of b-oxopropyl esters for catalysts 6g, 6h and 10 at
608C.[a]
applied, the performances of our catalysts are signifi-
cantly better than that of dinuclear complex 11, due
to the increased activation time of 11. Compared to
the mononuclear compound 10 the activity and pro-
ductivity is very similar to that of 6g and 6h.
For further testing and optimization reactions com-
plexes 6g, h were chosen, as they showed the highest Entry
activities and productivities. First of all, we wanted to
find out if the ruthenium loading can be further re-
duced. Therefore, the yields that could be obtained
after 24 h at 608C with ruthenium loadings between
0.1 and 1.0 mol% were determined (Table 4). Yields
of more than 80% could be reached with 0.5 mol% of
Product
Yield[b] [%]
6g
6h
10
1
3a
3g
96
92
24
92
6g or down to 0.25 mol% of 6h. With loadings of only
2
75
53
47
15
0.1 mol% both catalysts still achieved yields between
34–45%. Nearly no drop of productivity was observed
for 6h going from 1.0 mol% down to 0.5 mol%, which
can be explained with its incomplete solubility at
higher loadings.
3
3l
19
As in literature loadings of 1.0 mol% have been
usually applied,[6,11,29,31,33,46] we decided to use this
amount in further substrate screenings for reasons of
comparability, too.
Applying the optimized reaction conditions (608C,
1.0 mol%) somewhat more challenging propargylic al-
[a]
[b]
Reaction conditions: benzoic acid (1.0 mmol), propargylic
alcohol (2.0 mmol), acenaphthene (0.5 mmol), 24 h at
608C in toluene (1 mL).
The yields were determined by 1H NMR spectroscopy
applying acenaphthene as internal standard.
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
4075

UPDATES
Janine Jeschke et al.
the substrate. This fact was already reported to be
true for the applied carboxylic acids.[11] It is also inter-
esting to note that with complex 6h only about one
third of the yields compared to that of compound 6g
were achieved. These reduced yields are presumably
caused by steric hindrance of the CF3 groups in the
meta-position of the triarylphosphine ligands. As cata-
lyst 6g shows the highest productivities, even when
sterically more demanding substrates are converted,
this complex was chosen for all further substrate
screening reactions.
As it becomes evident from Table 5, even with the
most productive catalyst 6g reaction times of at least
24 h are necessary to reach full conversions of the
benzoic acid at a working temperature of 608C. This
prompted us to study the temperature dependent re-
action profiles (Figure 6). As it was already presented
in Figure 5, a nearly quantitative yield in the addition
of benzoic acid to propargylic alcohol was achieved
after 24 h at 608C. When raising the temperature by
108C the same yield is reached after only 9 h. By a fur-
ther increase of 108C the reaction time could even be
reduced down to 5 h.
For final substrate screening we decided to perform
the reactions with 1.0 mol% of catalyst 6g at 808C,
which allowed us to reduce the reaction times down
to approximately one quarter when compared to a re-
action temperature of 608C.
To assess the substrate scope of the reaction diverse
propargylic alcohols were treated with benzoic acid
under the optimized reaction conditions. Scheme 7
shows that next to the primary propargylic alcohol
prop-2-yn-1-ol (1a) also secondary (1b–f) and tertiary
propargylic alcohols (1g–l) can be successfully con-
verted into the corresponding b-oxopropyl esters with
Scheme 7. Scope of the propargylic alcohol in the formation
of b-oxopropyl esters.
good to excellent isolated yields. In comparison to
our previously reported studies on b-oxo ester synthe-
sis[33] we were not only able to obtain higher yields
but also to significantly reduce the reaction tempera-
ture and time.
The catalyst 6g exhibits productivities, for both
simple and challenging substrates, that often match or
even exceed those of other complexes known to pro-
mote this reaction. The hydrosoluble catalytic systems
{RuCl2(h6-C6H6)[PPh2(m-C6H4-SO3Na)]} (12)[27] and
trans-[RuCl2(h3:h3-C10H16)(PPh3)] (13)[47] of Cadierno
Figure 6. Temperature dependent reaction profiles for the
addition of benzoic acid to propargylic alcohol catalyzed by
6g.
4076
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 4069 – 4081

UPDATES
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo Esters
et al. show high productivities and tolerate a broad
range of functional groups at the substrates. But these
systems suffer from limitations in the use of bulky ter-
tiary alkynols.[27] So far, just with complex [RuCl2(p-
cymene){(R)}-BINOL-N,N-dibenzyl-phosphorami-
dite}] (14) reported by Bauer et al. acceptable yields
in the conversion of 1,1-diphenylprop-2-yn-1-ol (1i) to
benzoic acid 2-oxo-1,1-diphenylpropyl ester (3i) were
obtained.[28] All other systems failed in this conversion
as they could only detect trace amounts of the desired
product.[27,46] By applying catalyst 6g we could now
isolate 74% of product 3i in 4 h at 808C, whereas with
complex 14 just 68% after 5 h at 908C were achieved.
The group of Lynam succeeded with their ruthenium-
carboxylate complex [Ru(PPh3)2(OAc)2] (15) in the
conversion of the bulky steroid ethisterone. They
were able to isolate 53% of product 3l after 16 h at
1208C.[46] Compared to that, we could isolate 63% by
performing the reaction only at 1008C.
However, when alkynols with varying electronic
features (1c–f) were investigated, significant differen-
ces in the obtained yields of 3c–f were observed. Ca-
dierno et al. also evaluated the productivities when
applying aromatic propargylic alcohols with diverse
electronic properties. They came to the conclusion
that propargylic alcohols with electron-withdrawing
groups show higher reactivities when compared to
substrates with electron-donating functionalities.[27]
One could come to the same conclusion, when just
our results for products 3c–e were considered. Taking Figure 7. Comparison of the yield-time plots (top) and the
conversion-time plots (bottom) for the reaction of varying
para-substituted 1-phenylprop-2-yn-1-ols 1c–e with benzoic
acid at 808C in toluene. The conversion was determined by
measuring the amount of the propargylic alcohol.
also into account the low yield for the formation of
3f, this finding needs some additional explanation.
For this reason we followed the reactions to form 3c–
e over time. The respective yield-time and conver-
sion-time plots are depicted in Figure 7.
[27,28,47]
ꢀ
From the yield-time plot it can be seen that the re- cleavage of the C C bond
or a,b-unsaturated
action of benzoic acid with 1-(4-methoxyphenyl)prop- vinyl aldehydes arising from a Meyer–Schuster-type
2-yn-1-ol (1d) at 808C is already finished after 2 h. rearrangement[46,48] of the propargylic alcohol were
However, yields of only approximately 50% are observed. Both reaction pathways have already been
reached. On the contrary, when substrates with elec- reported to occur in the ruthenium-catalyzed addition
tron-withdrawing groups like 1-(4-chlorophenyl)prop- of carboxylic acids to propargylic alcohols.
2-yn-1-ol (1e) are used, the initial rate is lower, but
To complete our studies on different electronic in-
higher yields can be obtained. The observation of dif- fluences of the catalyst ligands and substrates in the
ferent initial reaction rates becomes even more appar- ruthenium-catalyzed b-oxo ester formation, we finally
ent, when the conversions of the various propargylic studied the impact of the carboxylic acid. Therefore,
alcohols are followed over time. Figure 7 shows that a correlation of the Hammett value s1 and the ob-
the more electron-donating the functionalities are, the tained yields in the conversion of a series of para-sub-
higher is the conversion of the respective alkynol. stituted benzoic acids p-X-C6H4-CO2H (X=NMe2,
This fact can be explained by a facilitated activation OMe, CH3, H, Cl, C(O)CH3, CF3, NO2) was estab-
ꢀ
of the electron-rich C C triple bond by coordination lished (Figure 8). The positive 1 value in Figure 8 re-
of the propargylic alcohol to the electrophilic rutheni- veals electron-withdrawing groups on the benzoic
um atom. However, the low yields obtained with elec- acid to modestly increase the productivity. This result
tron-rich substrates suggest that not only the forma- indicates that not the nucleophilic attack of the acid is
À
tion of the b-oxo esters is accelerated, but also that rate-limiting, but the cleavage of the O H bond
undesired side reactions take place. For this reason through deprotonation or oxidative addition of the
the crude reaction mixtures were analyzed by GC- acid to the Ru catalyst. Unfortunately, we were not
MS. Thereby, olefinic side products resulting from the able to clarify which of the latter paths takes place, as
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
4077

UPDATES
Janine Jeschke et al.
still be effectively carried out at catalyst loadings
down to 0.1 mol% or reaction temperatures down to
508C. The screening of the electronic nature of the
phosphine ligands revealed a considerably influence
on the activities of the resulting catalysts. All substi-
tuted triarylphoshine complexes gave better yields
than PPh3 complex 6d. But no general correlation be-
tween the basicity of the phosphine ligand and the
catalytic performance could be established. Of all
tested catalysts, complex 6g with electron-withdrawing
CF3 groups, was found to be the most active and pro-
ductive. This catalyst effectively promotes the conver-
sion of a broad range of simple as well as challenging
substrates in yields that often match or even exceed
those of established literature systems. Additionally,
we did examine the electronic impact of the sub-
strates. The Hammett study demonstrated that elec-
tron-withdrawing benzoic acids modestly increase the
productivity. In contrast to that, the electronic influ-
ence of the alkynol was much more decisive, which is
why we consider the activation of the propargylic al-
cohol by the ruthenium to be the rate-determining
step. Furthermore, we found that alkynols with elec-
tron-donating functionalities do not only accelerate
the desired reaction, but also support side reactions
Figure 8. Hammett plot of the coupling reaction of para-sub-
stituted benzoic acids p-X-C6H4-CO2H with propargylic
alcohol. Linear regression: y=37x+64.8; R2 =0.91.
ꢀ
like the cleavage of the C C bond or Meyer–Schus-
the complexes 6a–h remained nearly unaffected after ter-type rearrangements. For this reason propargylic
the reaction and the concentration of the real catalyt- alcohols with electron-withdrawing substituents need
ic species was too low to be detected by in situ IR or longer reaction times, but can under certain circum-
NMR spectroscopic studies. Additionally, the coordi- stances lead to higher yields.
nation of the propargylic alcohol to the ruthenium
complex seems to be the rate-determining step, as in-
dicated by the strong impact of the nature of alkynol, Experimental Section
which is why no possible ruthenium-hydride inter-
mediate suggesting an oxidative addition could be de- General Information
tected.
Compounds 1d–f,[49,50] 5b, c[51] and 5e–h[51] were prepared in
a modified reaction protocol according to published proce-
It is also interesting to note that the carboxylate
groups bound to the initial catalyst complex are con-
dures. Toluene was dried by a solvent-purification system
verted, too, as confirmed by H NMR spectroscopy.
This means that in our case, by applying a catalyst
loading of 1.0 mol%, the yields are limited to 98%
when acids distinct from benzoic acid are converted.
1
(MB SPS-800, MBraun). All other chemicals were pur-
chased from commercial suppliers and were used as re-
ceived. If necessary, solvents were deoxygenated by standard
procedures. For column chromatography silica with a particle
size of 40–60 mm (230–400 mesh (ASTM), Fa. Macherey–
Nagel) was used.
Conclusions
Instruments
The
ruthenium
complexes
of
the
type
NMR spectra were recorded with a Bruker Advance III 500
spectrometer operating at 500.3 MHz for H, 125.7 MHz for
Ru(CO)2(PR3)2(O2CPh)2 [6a, R=n-Bu; 6b, R=p-
MeO-C6H4; 6c, R=p-Me-C6H4; 6d, R=Ph; 6e, R=p-
Cl-C6H4; 6f, R=m-Cl-C6H4; 6g, R=p-CF3-C6H4; 6h,
R=m,m’-(CF3)2C6H3] were found to be highly effec-
tive catalysts in the addition of carboxylic acids to
propargylic alcohols to give valuable b-oxo esters. In
comparison to our previously reported catalytic stud-
ies, we were able to improve the productivities by si-
multaneous reduction of the reaction time and tem-
1
13C{1H} and 202.5 MHz for 31P{1H} spectra in the Fourier
transform mode at 298 K. Chemical shifts are reported in d
(ppm) downfield from tetramethylsilane with the solvent as
reference signal (1H NMR, CHCl3 d=7.26, acetone-d6 d=
2.05; 13C{1H} NMR, CDCl3 d=77.16, acetone-d6 d=206.26;
31P{1H} NMR, standard external relative to 85% H3PO4 d=
0.0). FT-IR spectra were recorded using a FT Nicolet IR
200 instrument. The melting points were determined using
perature.[33] We could also show that the reactions can a Gallenkamp MFB 595 010M melting point apparatus. Ele-
4078
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 4069 – 4081

UPDATES
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo Esters
mental analyses were measured with a Thermo FlashAE
1112 instrument. High-resolution mass spectra were record-
ed on a Bruker Daltonite micrOTOF-QII spectrometer
using electro-spray ionization (ESI).
the obtained residue was suspended in n-hexane (10 mL).
The precipitate was collected by filtration, washed with di-
ethyl ether (2”5 mL) and dried under vacuum.
Typical Procedure for b-Oxopropyl Ester Synthesis
Single-Crystal X-ray Diffraction Analysis
In a screw-capped vial, benzoic acid (122 mg, 1.0 mmol),
propargylic alcohol (112 mg, 2.0 mmol), acenaphthene
(77 mg, 0.5 mmol) and the catalyst (0.01 mmol) were dis-
solved in toluene (1 mL). The sealed vial was immersed in
a heating mantle preheated to 608C. After 24 h all volatiles
were evaporated under reduced pressure. The yields of the
optimization experiments were determined by 1H NMR
spectroscopy applying acenaphthene as internal standard.
However, analytically pure products were isolated by
column chromatography on silica gel. All catalytic results
have been verified by at least two independent experiments.
Diffraction data were collected with an Oxford Gemini S
diffractometer at ꢁ110 K with graphite-monochromated Mo
Ka radiation (l=0.71073 Š) (6a, b, e–h, 8b, e, g, 9h) and Cu
Ka radiation (l=1.54184 Š) (6c, 9g) using oil-coated shock-
cooled crystals. The structures were solved by direct meth-
ods and refined by full-matrix least-squares procedures on
F2.[52,53] All non-hydrogen atoms were refined anisotropically,
and a riding model was employed in the treatment of the
hydrogen atom positions. Graphics of the molecular struc-
tures have been created by using SHELXTL[53] and
ORTEP.[54]
CCDC 1413142 (6a), CCDC 1413143 (6b), CCDC
1413144 (6c), CCDC 1413145 (6e), CCDC 1413146 (6f),
CCDC 1413147 (6g), CCDC 1413148 (6h), CCDC 1413149
(8b), CCDC 1413150 (8e), CCDC 1413151 (8g), CCDC
1413152 (9g) and CCDC 1413153 (9h) contain the supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
Supporting Information
Detailed experimental procedures, characterization data,
crystal data and structure refinement for all ruthenium com-
plexes 6a–h, 8b–h and 9g, h, as well as characterization data,
1H and 13C NMR spectra of catalysis products 3a–l can be
found in the Supporting Information.
Acknowledgements
General Preparation Procedure for Ru(CO)3(PR3)2
(8b–h)
This work was in part supported by the Fonds der Chemi-
schen Industrie. J. J. and M.K. thank the Fonds der Chemi-
schen Industrie for Chemiefonds fellowships. We thank Her-
aeus for generous gifts of chemicals.
The complexes 8b–h were prepared by modified literature
procedures.[36] To a hot solution of RuCl3·xH2O (390 mg,
1.49 mmol), the respective phosphine (9.0 mmol) and KOH
(600 mg, 10.7 mmol) dissolved in 2-methoxyethanol (100–
250 mL) was added aqueous formaldehyde (30 mL, 37% wt)
in a single portion. The solution was refluxed for 2 to 18 h
after which time the product precipitated as yellow micro-
crystals. The product was filtered off, washed with ethanol
(1”10 mL), water (1”10 mL), ethanol (2”10 mL) and n-
hexane (1”10 mL) and dried under vacuum. During the
preparation of 8g, h the dihydrido complexes 9g, h could be
obtained in minor yields as side products, especially when
low solvent volumes (<150 mL) were applied.
References
[1] B. M. Trost, M. U. Frederiksen, M. T. Rudd, Angew.
Chem. 2005, 117, 6788–6825; Angew. Chem. Int. Ed.
2005, 44, 6630–6666.
[2] J. Grunes, J. Zhu, G. A. Somorjai, Chem. Commun.
2003, 2257–2260.
[3] B. M. Trost, F. D. Toste, A. B. Pinkerton, Chem. Rev.
2001, 101, 2067–2096.
[4] T. Naota, H. Takaya, S.-I. Murahashi, Chem. Rev. 1998,
98, 2599–2660.
General Preparation Procedure for
Ru(CO)2(PR3)2(O2CPh)2 – Method A
[5] M. Beller, J. Seayad, A. Tillack, H. Jiao, Angew. Chem.
2004, 116, 3448–3479; Angew. Chem. Int. Ed. 2004, 43,
3368–3398.
[6] C. Bruneau, P. H. Dixneuf, Chem. Commun. 1997, 507–
512.
[7] O. J. S. Pickup, I. Khazal, E. J. Smith, A. C. Whitwood,
J. M. Lynam, K. Bolaky, T. C. King, B. W. Rawe, N.
Fey, Organometallics 2014, 33, 1751–1761.
A solution of Ru3(CO)12 (200 mg, 313 mmol) and the respec-
tive phosphine (2.50 mmol) in 4-methylpentan-2-one
(18 mL) was refluxed for 8 h. Benzoic acid (306 mg,
2.50 mmol) was added and the solution refluxed for further
16 h. After solvent removal under reduced pressure, the res-
idue was washed with n-hexane and diethyl ether to give
a colorless solid, which was dried under vacuum.
[8] J. M. Lynam, Chem. Eur. J. 2010, 16, 8238–8247.
[9] C. Bruneau, P. H. Dixneuf, Metal Vinylidenes and Alle-
nylidenes in Catalysis, Wiley-VCH, Weinheim, 2008.
[10] a) C. Ruppin, P. H. Dixneuf, Tetrahedron Lett. 1986, 27,
6323–6324; b) M. Rotem, Y. Shvo, J. Organomet.
Chem. 1993, 448, 189–204; c) H. Doucet, N. Derrien, Z.
Kabouche, C. Bruneau, P. H. Dixneuf, J. Organomet.
General Preparation Procedure for
Ru(CO)2(PR3)2(O2CPh)2 – Method B
A suspension of Ru(CO)3(PR3)2 (8e–h) (400 mg) and benzo-
ic acid (4 equiv.) in 4-methylpentan-2-one (10 mL) was
stirred for 1 h at 1008C. The solvent of the obtained clear
yellow solution was removed under reduced pressure and
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
4079

UPDATES
Janine Jeschke et al.
Chem. 1998, 551, 151–157; d) K. Melis, P. Samulkiewicz,
J. Rynkowski, F. Verpoort, Tetrahedron Lett. 2002, 43,
2713–2716; e) K. Melis, F. Verpoort, J. Mol. Catal. A:
Chem. 2003, 194, 39–47; f) L. J. Gooßen, J. Paetzold, D.
Koley, Chem. Commun. 2003, 706–707; g) S. Ye, W. K.
Leong, J. Organomet. Chem. 2006, 691, 1117–1120; h) J.
Tripathy, M. Bhattacharjee, Tetrahedron Lett. 2009, 50,
4863–4865; i) F. Nicks, R. Aznar, D. Sainz, G. Muller,
A. Demonceau, Eur. J. Org. Chem. 2009, 5020–5027;
j) S. T. Tan, W. Y. Fan, Eur. J. Inorg. Chem. 2010, 4631–
4635; k) S. Berger, E. Haak, Tetrahedron Lett. 2010, 51,
6630–6634; l) C. S. Yi, J. Organomet. Chem. 2011, 696,
76–80; m) M. Kawatsura, J. Namioka, K. Kajita, M. Ya-
mamoto, H. Tsuji, T. Itoh, Org. Lett. 2011, 13, 3285–
3287; n) M. Nishiumi, H. Miura, K. Wada, S. Hosoka-
wa, M. Inoue, ACS Catal. 2012, 2, 1753–1759; o) K.-C.
Cheung, W.-L. Wong, M.-H. So, Z.-Y. Zhou, S.-C. Yan,
K.-Y. Wong, Chem. Commun. 2013, 49, 710–712; p) H.
Schrçder, G. A. Strohmeier, M. Leypold, T. Nuijens,
P. J. L. M. Quaedflieg, R. Breinbauer, Adv. Synth.
Catal. 2013, 355, 1799–1807.
Y. B. Shaikh, V. B. Ningdale, M. P. Desai, D. R. Bir-
hade, Tetrahedron Lett. 2009, 50, 2893–2894.
[24] A. S. Demir, N. Camkerten, H. Akgun, C. Tanyeli,
A. S. Mahasneh, D. S. Watt, Synth. Commun. 1990, 20,
2279–2289.
[25] C. Schreiner, J. Jeschke, B. Milde, D. Schaarschmidt, H.
Lang, J. Organomet. Chem. 2015, 785, 32–43.
[26] Y. Kita, H. Maeda, K. Omori, T. Okuno, Y. Tamura,
Synlett 1993, 273–274.
[27] V. Cadierno, J. Francos, J. Gimeno, Green Chem. 2010,
12, 135–143.
[28] S. Costin, N. Rath, E. Bauer, Adv. Synth. Catal. 2008,
350, 2414–2424.
[29] C. Darcel, C. Bruneau, P. H. Dixneuf, G. Neef, J.
Chem. Soc. Chem. Commun. 1994, 333–334.
[30] T. Mitsudo, Y. Hori, Y. Yamakawa, Y. Watanabe, J.
Org. Chem. 1987, 52, 2230–2239.
[31] C. Bruneau, Z. Kabouche, M. Neveux, B. Seiller, P. H.
Dixneuf, Inorg. Chim. Acta 1994, 222, 155–163.
[32] B. Milde, T. Rüffer, H. Lang, Inorg. Chim. Acta 2012,
387, 338–345.
[33] J. Jeschke, C. Gäbler, M. Korb, T. Rüffer, H. Lang,
Eur. J. Inorg. Chem. 2015, 2939–2947.
[11] D. Devanne, C. Ruppin, P. H. Dixneuf, J. Org. Chem.
1988, 53, 925–926.
[12] a) G. Schwenker, K. Stiefvater, Arch. Pharm. (Wein-
heim) 1991, 324, 547–550; b) G. Scheid, W. Kuit, E.
Ruijter, R. V. A. Orru, E. Henke, U. Bornscheuer,
L. A. Wessjohann, Eur. J. Org. Chem. 2004, 1063–1074;
c) P. A. Carpino, D. A. Griffith, S. Sakya, R. L. Dow,
S. C. Black, J. R. Hadcock, P. A. Iredale, D. O. Scott,
M. W. Fichtner, C. R. Rose, R. Day, J. Dibrino, M.
Butler, D. B. DeBartolo, D. Dutcher, D. Gautreau, J. S.
Lizano, R. E. O’Connor, M. A. Sands, D. Kelly-Sulli-
van, K. M. Ward, Bioorg. Med. Chem. Lett. 2006, 16,
731–736; d) H.-L. Lu, Z.-W. Wu, S.-Y. Song, X.-D.
Liao, Y. Zhu, Y.-S. Huang, Org. Process Res. Dev. 2014,
18, 431–436.
[13] B. M. Trost, H. Urabe, J. Org. Chem. 1990, 55, 3982–
3983.
[14] I. A. Kaluzna, J. D. Rozzell, S. Kambourakis, Tetrahe-
dron: Asymmetry 2005, 16, 3682–3689.
[15] R. Schwyzer, B. Iselin, M. Feurer, Helv. Chim. Acta
1955, 38, 69–79.
[34] a) L. J. Gooßen, N. Rodríguez, K. Gooßen, Angew.
Chem. 2008, 120, 3144–3164; Angew. Chem. Int. Ed.
2008, 47, 3100–3120; b) C. Bruneau, P. H. Dixneuf,
Angew. Chem. 2006, 118, 2232–2260; Angew. Chem.
Int. Ed. 2006, 45, 2176–2203.
[35] M. Bianchi, P. Frediani, U. Matteoli, G. Menchi, F. Pia-
centi, G. Petrucci, J. Organomet. Chem. 1983, 259, 207–
214.
[36] a) N. Ahmad, S. D. Robinson, M. F. Uttley, J. Chem.
Soc. Dalton Trans. 1972, 843–847; b) N. Ahmad, J. J.
Levison, S. D. Robinson, M. F. Uttley, Inorg. Synth.
1974, 15, 50; c) J. P. Dunne, D. Blazina, S. Aiken, H. A.
Carteret, S. B. Duckett, J. A. Jones, R. Poli, A. C. Whit-
wood, Dalton Trans. 2004, 3616–3628.
[37] P. S. Hallman, B. R. McGarvey, G. Wilkinson, J. Chem.
Soc. A 1968, 3143–3150.
[38] a) H. Samouei, V. V. Grushin, Organometallics 2013,
32, 4440–4443; b) N. A. Owston, A. J. Parker, J. M. J.
Williams, Chem. Commun. 2008, 624–625; c) T. D.
Nixon, M. K. Whittlesey, J. M. J. Williams, Dalton
Trans. 2009, 753–762.
[39] a) J. P. Collman, W. R. Roper, J. Am. Chem. Soc. 1965,
87, 4008–4009; b) B. F. G. Johnson, R. D. Johnston, J.
Lewis, I. G. Williams, J. Chem. Soc. A 1971, 689–691;
c) S. D. Robinson, M. F. Uttley, J. Chem. Soc. Dalton
Trans. 1973, 1912–1920; d) A. Dobson, S. D. Robinson,
M. F. Uttley, J. Chem. Soc. Dalton Trans. 1975, 370–
377; e) M. Rotem, Z. Stein, Y. Shvo, J. Organomet.
Chem. 1990, 387, 95–101; f) M. Pizzotti, S. Cenini, F.
Porta, J. Organomet. Chem. 1993, 448, 205–209.
[40] O. Kühl, Phosphorus-31 NMR Spectroscopy, Springer,
Berlin, 2008.
[16] C. Bruneau, M. Neveux, Z. Kabouche, C. Ruppin, P. H.
Dixneuf, Synlett 1991, 755–763.
[17] a) W. O. Erhun, Pharmazie 1983, 38, 790; b) M. M. Sal-
unkhe, A. R. Sande, A. S. Kanade, P. P. Wadgaonkar,
Synth. Commun. 1997, 27, 2885–2891.
[18] a) M. A. Ashraf, M. A. Jones, N. E. Kelly, A. Mullaney,
J. S. Snaith, I. Williams, Tetrahedron Lett. 2003, 44,
3151–3154; b) M. A. Ashraf, A. G. Russell, C. W. Whar-
ton, J. S. Snaith, Tetrahedron 2007, 63, 586–593.
[19] a) G. K. D. Erdmann, K. Schuehrer, W. Koch, German
Patent, DE 2116416, 1972; b) B. Schickmous, J. Chris-
toffers, Eur. J. Org. Chem. 2014, 4410–4416.
[20] V. Stoeck, W. Schunack, Arch. Pharm. (Weinheim)
1976, 309, 421–425.
[41] H. G. Metzinger, Org. Magn. Reson. 1971, 3, 485–494.
[42] R. K. Harris, Can. J. Chem. 1964, 42, 2275–2281.
[43] G. B. Deacon, R. J. Phillips, Coord. Chem. Rev. 1980,
33, 227–250.
[44] The rms deviation of the calculated C2O2 plane is
rather high with up to 0.0794, due to a distortion of the
[21] P. Yates, R. S. Grewal, P. C. Hayes, J. F. Sawyer, Can. J.
Chem. 1988, 66, 2805–2815.
[22] T. Shinada, T. Kawakami, H. Sakai, I. Takada, Y.
Ohfune, Tetrahedron Lett. 1998, 39, 3757–3760.
[23] M. G. Kulkarni, S. M. Bagale, M. P. Shinde, D. D. Gaik-
wad, A. S. Borhade, A. P. Dhondge, S. W. Chavhan,
4080
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 4069 – 4081

UPDATES
Atom Economic Ruthenium-Catalyzed Synthesis of Bulky b-Oxo Esters
equatorial plane and the ligands slightly bending out of
Cadierno, P. Crochet, S. E. Garcia-Garrido, J. Gimeno,
this plane.
Dalton Trans. 2010, 39, 4015–4031.
[49] H.-S. M. Siah, M. Kaur, N. Iqbal, A. Fiksdahl, Eur. J.
Org. Chem. 2014, 1727–1740.
[45] A CSD database search based on the equal substitution
pattern of three phosphines, one carbonyl ligand and
À
two hydrogen atoms results in 14 examples with Ru H
[50] J. Park, J. Yun, J. Kim, D.-J. Jang, C. H. Park, K. Lee,
distances of 1.465–1.865 Š, an average of 1.69(12) Š
with the median at 1.66 Š. Two values above 2.33 Š
have been omitted.
Synth. Commun. 2014, 44, 1924–1929.
[51] Q. Zhang, Y. Yang, S. Zhang, Chem. Eur. J. 2013, 19,
10024–10029.
[52] G. M. Sheldrick, SHELXL-2013, Program for Crystal
Structure Refinement, Universität Gçttingen, Germany,
2013.
[53] G. M. Sheldrick, Acta Crystallogr. Sect. A 2008, 64,
112–122.
[46] N. P. Hiett, J. M. Lynam, C. E. Welby, A. C. Whitwood,
J. Organomet. Chem. 2011, 696, 378–387.
[47] V. Cadierno, J. Francos, J. Gimeno, Organometallics
2011, 30, 852–862.
[48] a) M. Picquet, C. Bruneau, P. H. Dixneuf, Chem.
Commun. 1997, 1201–1202; b) D. A. Engel, G. B.
Dudley, Org. Biomol. Chem. 2009, 7, 4149–4158; c) V.
[54] L. J. Farrugia, J. Appl. Crystallogr. 2012, 45, 849–854.
Adv. Synth. Catal. 2015, 357, 4069 – 4081
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
4081