Acceptorless, neat, ruthenium-catalyzed dehydrogenative cyclization of diols to lactones

Article abstract of DOI:10.1021/om048983m

We report the dehydrogenation of 1,4-butanediol to γ-butyrolactone catalyzed by soluble ruthenium complexes without solvent or a hydrogen acceptor. An alkylphosphine version of ruthenium bis-phosphine diamine catalysts has been prepared and was found to be the longest-lived catalyst for the conversion of 1,4-butanediol to γ-butyrolactone. The catalytic production of γ-butyrolactone from 1,4-butandiol with this catalyst is simple to conduct, environmentally friendly, and highly efficient.

Full text of DOI:10.1021/om048983m

Organometallics 2005, 24, 2441-2446
2441
Acceptorless, Neat, Ruthenium-Catalyzed
Dehydrogenative Cyclization of Diols to Lactones
Jing Zhao and John F. Hartwig*
Department of Chemistry, Yale University, P.O. Box 208107,
New Haven, Connecticut 06520-8107
Received December 22, 2004
We report the dehydrogenation of 1,4-butanediol to γ-butyrolactone catalyzed by soluble
ruthenium complexes without solvent or a hydrogen acceptor. An alkylphosphine version of
ruthenium bis-phosphine diamine catalysts has been prepared and was found to be the
longest-lived catalyst for the conversion of 1,4-butanediol to γ-butyrolactone. The catalytic
production of γ-butyrolactone from 1,4-butandiol with this catalyst is simple to conduct,
environmentally friendly, and highly efficient.
Scheme 1. Catalytic Dehydrogenation with
Hydrogen Acceptors
Introduction
γ-Butyrolactone is an important chemical intermedi-
ate and solvent. γ-Butyrolactone has been manufactured
mainly by dehydrogenation of 1,4-butanediol with het-
erogeneous copper catalysts, hydrogenation of maleic
anhydride, and hydrogenation of maleic esters.1 The
synthesis of γ-butyrolactone from 1,4-butanediol is
particularly attractive because it does not produce any
waste.1 The hydrogen byproduct can be reused after
simple purification. However, heterogeneous catalysts
generally do not exhibit high selectivity for γ-butyro-
lactone, and tuning of the catalyst activity can be
difficult. In addition, most heterogeneous catalytic cy-
clizations of 1,4-butanediol occur with gaseous diol.
Because the reactants and the hydrogen byproduct
reside in the same gas phase, it is challenging to drive
the formation of γ-butyrolactone by the extrusion of
hydrogen from the system.1-3
Many homogeneous catalysts have been developed for
the dehydrogenation of diols to lactones in the presence
of hydrogen acceptors.4-6 Murahashi and co-workers
reported the conversion of 1,4-butanediol to γ-butyro-
lactone in 99% yield with RuH2(PPh3)4 as a catalyst and
acetone as hydrogen acceptor.4 Lin et al. reported this
reaction with the iridium polyhydride IrH5(iPr3P)2 in
91% yield with acetone as a hydrogen acceptor.5 Re-
cently, Suzuki and Hiroi reported oxidative lactonization
of diols with a catalyst containing an amino alcohol
ligand. A variety of 1,4- or 1,5-diols were converted in
this work to lactones with acetone or butanone as
hydrogen acceptor. The yield of γ-butyrolactone was
96%.6
without a hydrogen acceptor. In contrast to the cycliza-
tions with hydrogen acceptors, few examples of catalytic
dehydrogenation of 1,4-butanediol to γ-butyrolactone
have been reported without a hydrogen acceptor. Mura-
hashi and co-workers reported that 1,4-butanediol was
converted to γ-butyrolactone in the presence of RuH2-
(PPh3)4 as catalyst in only 63% yield without a hydrogen
acceptor.4 Similarly, Lin et al. obtained γ-butyrolactone
in only 54% yield from 1,4-butanediol without a hydro-
gen acceptor.5
The scarcity of examples and low yields reported for
acceptorless catalytic dehydrogenation of 1,4-butanediol
probably results from an unfavorable equilibrium for
the alcohol dehydrogenation. Because the dehydroge-
nation of diols to lactones is endothermic (14.7 kcal/
mol),1 it must be coupled with an exothermic reaction,
such as hydrogenation of a sacrificial ketone, or con-
ducted in an open system to obtain high yields.1
Likewise, the dehydrogenation of alcohols to ketones
and alkanes to alkenes without a hydrogen acceptor is
unfavorable thermodynamically. These reactions have
been reported in an open system,7,8 but the acceptorless
dehydrogenation of secondary alcohols and alkanes has
been more challenging to develop than transfer hydro-
genation in each case (Scheme 2).
Our strategy for the development of improved cata-
lysts for dehydrogenation of 1,4-butanediol began with
consideration of the advances in homogeneous hydro-
genation of ketones during the past 20 years.9,10 The
ruthenium complexes with a diphosphine and a diamine
An oxidative cyclization suitable for large-scale pro-
duction of γ-butyrolatone must occur in a neat system
(1) Gra¨fje, H.; Ko¨rnig, W.; Weitz, H.; Reiss, W. In Ullmann’s
Encyclopedia of Industrial Chemistry, 6th ed.; Wiley-VCH: Weinheim,
2000.
(2) Oka, S. Bull. Chem. Soc. Jpn. 1961, 34, 12-14.
(3) Oka, S. Bull. Chem. Soc. Jpn. 1962, 35, 986-989.
(4) Murahashi, S. I.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J. Org.
Chem. 1987, 52, 4319.
(7) Zhang, J.; Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.;
Milstein, D. Organometallics 2004, 23, 4026-4033.
(8) Fujii, T.; Saito, Y. J. Chem. Soc., Chem. Commun. 1990, 757-
758.
(5) Lin, Y. R.; Zhu, X. C.; Zhou, Y. F. J. Organomet. Chem. 1992,
429, 269.
(9) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40-
73.
(6) Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K. Org. Lett. 2002,
4, 2361.
(10) Pettinari, C.; Marchetti, F.; Martini, D. in Comprehensive
Coordination Chemistry II 2004, 9, 75-139.
10.1021/om048983m CCC: $30.25 © 2005 American Chemical Society
Publication on Web 04/15/2005

2442 Organometallics, Vol. 24, No. 10, 2005
Zhao and Hartwig
Table 1. Conversion of 1,4-Butanediol to
Scheme 2. Relationship between Hydrogenation
and Dehydrogenation with and without an
Acceptor
γ-Butyrolactone Catalyzed by Ruthenium
Dihydride and Bis-2-methylallyl Complexesa
ratio
entry
catalyst
time (h) (diol:GBL)b
1
2
3
4
5
6
7
8
RuH2(PMe3)4 (1)
10
10
10
12
10
10
10
10
0:100
0:97
0:100
19:81
32:57
4:93
RuH2(PEt3)4 (2)
RuH2(PBu3)4 (3)
RuH2(PPh3)4 (4)
ligand introduced by Ikariya and Noyori are particularly
efficient and have found wide applications.11 These
catalysts operate by a novel metal-ligand difunctional
mechanism involving the transfer of hydrogen through
a cyclic transition state without coordination of the
ketone to the metal or generation of an alkoxide
intermediate.12 Based on microscopic reversibility, the
same mechanism must be followed for the dehydroge-
nation of alcohols.
RuH2(DMPE)2 (5)
(PMe3)2Ru(2-methylallyl)2 (6a)
(DMPE)Ru(2-methylallyl)2 (6b)
(DIOP)Ru(2-methylallyl)2 (6d)
1:99
9:76
a Reaction conditions: catalyst 0.005 mmol and 1.1 mmol of 1,4-
butanediol were refluxed at 205 °C for 10-12 h in a capped vial.
b Ratios determined by GC. When the sum of the values is less
than 100%, other products were observed in the GC trace.
phosphine ligands because alkylphosphines are more
stable at high temperatures than arylphosphines.16,17
Table 1 summarizes our results on the catalytic
dehydrogenation of 1,4-butanediol to γ-butyrolactone
without a hydrogen acceptor and catalyzed by dihydride
and bisallyl ruthenium complexes with alkylphosphines
and several arylphosphines. Three complexes in this
series (1, 2, 3) catalyzed the dehydrogenation efficiently.
In contrast to the high activity of ruthenium dihydride
complexes with alkylmonophosphines (1, 2, 3), RuH2-
(PPh3)4 (4) and RuH2(DMPE)2 (5) (DMPE ) 1,2-bis-
(dimethylphosphino)ethane) displayed only moderate
catalytic activity for this reaction.
Catalytic Studies with Ruthenium Allyl Com-
plexes. To test the activity of ruthenium complexes that
would contain only two phosphorus donors, we synthe-
sized several (bisphosphine)Ru(2-methylallyl)2 com-
plexes (6) and evaluated their activity for the conversion
of 1,4-butanediol to γ-butyrolactone. We anticipated that
the 2-methylallyl ligand would react with the alcohol
by nucleophilic attack and would be released as an allyl
alcohol. Alternatively, it could react with a hydride
generated by â-hydrogen elimination and would be
released as an olefin. A subset of the (bisphosphine)-
Ru(2-methylallyl)2 complexes (6) catalyzed the dehy-
drogenation of 1,4-butanediol to γ-butyrolactone. Most
of the complexes were only modestly reactive for this
process, but (PMe3)2Ru(η3-(CH2)2CHCH3)2 (6a) and
(DMPE)Ru(η3-(CH2)2CHCH3)2 (6b) were both excellent
catalysts for the conversion of 1,4-butanediol to γ-bu-
tyrolactone (Table 1).
The most active catalysts for the forward hydrogena-
tion reaction need not be the most active catalysts for
the reverse dehydrogenation because the concentration
of reagents in the two processes are different. Thus, the
major transition metal complex present in the system
and the turnover-limiting step may be different for the
forward and reverse reactions. This difference between
the activities of catalysts for reactions in the forward
and reverse directions is well established in the field of
enzyme kinetics.13 Nevertheless, we thought that highly
active ketone hydrogenation catalysts would be a useful
starting point for the dehydrogenation of 1,4-butane diol
to γ-butyrolatone. Indeed, several complexes with diphos-
phines and diamines reacted with rates and turnover
numbers that exceed those of any previously reported
system. For example, a ruthenium complex containing
an aliphatic phosphine and a diamine generated the
product with high conversion and selectivity and 17 500
turnovers.
Results and Discussion
Initial Catalyst Design: Catalytic Studies with
Ruthenium Dihydrides. Prior to our work, Murahashi
and co-workers demonstrated that RuH2(PPh3)4 is an
effective catalyst for the conversion of 1,4-butanediol to
γ-butyrolactone.4,14 Takahashi et al. at Mitsubishi Chemi-
cal Corporation reported that several ruthenium com-
plexes prepared from Ru(acac)3 and alkylphosphines
under hydrogen-generated γ-butyrolactone from 1,4-
butanediol in high yield without a hydrogen acceptor.15
Because refluxing conditions are required to release
dihydrogen to allow the reaction to proceed to high
conversion, the reaction must be conducted at the
boiling point of γ-butyrolactone, 205 °C. Thus, we set
out to study ruthenium dihydride complexes with alkyl-
Reaction Mechanism and Identification of a
Potential Mode of Catalyst Decomposition. A likely
mechanism for the reaction catalyzed by Ru dihydride
complexes involves an alkoxide intermediate, as shown
in Scheme 4. In this mechanism, phosphine dissociation
is followed by coordination of the alcohol. Proton trans-
fer would yield a ruthenium alkoxide with a coordinated
dihydrogen, and dissociation of hydrogen would gener-
ate a ruthenium alkoxide.18 â-Hydrogen elimination
(11) 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.
(12) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97.
(13) Jencks, W. P. Catalysis in Chemistry and Enzymology; McGraw-
Hill: New York, 1969.
(14) Hara, Y.; Kusaka, H.; Inagaki, H.; Takahashi, K.; Wada, K. J.
Catal. 2000, 194, 188-197.
(15) Utsunomiya, M.; Takahashi, K.; Kawakami, K. (Mitsubishi
Chemical Corp.) Jpn. Kokai Tokyo Koho; Japan: JP, 2003, 7 pp.
(16) Burk, M. J.; Crabtree, R. H. J. Am. Chem. Soc. 1987, 109, 8025-
8032.
(17) Garrou, P. E. Chem. Rev. 1985, 85, 171-185.
(18) Vandersluys, L. S.; Kubas, G. J.; Caulton, K. G. Organometallics
1991, 10, 1033-1038.

Ru-Catalyzed Dehydrogenative Cyclization of Diols
Organometallics, Vol. 24, No. 10, 2005 2443
Scheme 3. Catalyst Structures
Scheme 5
Scheme 6
Table 2. Conversion of 1,4-Butanediol to
γ-Butyrolactone Catalyzed by Ruthenium
Bisphosphine Diamine Complexes and Shvo
Complexesa
ratio
entry
catalyst
Shvo dimer (12)
Shvo amide analogue (13)
trans-RuHCl(tmen)(BINAP) (14)
(DPPF)RuCl2(eda) (15)
(DIOP)RuCl2(eda) (16)
time (h) (diol:GBL)b
1
2
3
4
5
6
7
12
10
10
10
10
10
10
13:87
77:1
7:67
31:69
0:97
19:91
0:99
Scheme 4
(PPh3)2RuCl2(eda) (17)
(PMe3)2RuCl2(eda) (18)
a Reaction conditions: catalyst 0.005 mmol and 1.1 mmol of 1,4-
butanediol were heated at 205 °C for 10-12 h in a capped vial.
b Ratios determined by GC. When the sum of the values is less
than 100%, other products were observed in the GC trace. eda )
ethylenediamine, tmen ) tetramethylethylenediamine.
The formation of RuH2(CO)(PMe3)3 (7) in the catalytic
system can be rationalized by the mechanism in Scheme
6. The aldehyde generated by the dehydrogenation
process can undergo oxidative addition to ruthenium to
give a hydrido acyl Ru complex. Deinsertion of CO would
then give an alkyl carbonyl complex, which would
undergo reductive elimination of alkane to form a
ruthenium carbonyl complex. The generation of CO
ligands from alcohols is relatively common,18 and this
pathway for catalyst degradation was noted by Mura-
hashi and co-workers during their studies on the dehy-
drogenation of primary alcohols to esters catalyzed by
RuH2(PPh3)4.
We evaluated the reactivity of RuH2(CO)(PMe3)3 (7)
for the dehydrogenation of 1,4-butanediol to γ-butyro-
lactone to determine if it was an active or inactive form
the catalyst. This complex was reactive as a catalyst
and was one of the catalysts that exhibited the highest
turnover numbers (Table 2). These observations suggest
that conversion of the complexes with only phosphines
as dative ligands to complexes with a combination of
phosphines and carbonyls as dative ligands is facile.
Although we could not confidently assign a signal to a
bisphosphine dicarbonyl ruthenium complex, we sus-
pected that the bisphosphine dicarbonyl complex would
be less reactive than the monocarbonyl compound and
would serve as a pathway for catalyst deactivation.
Dissociation of ligand would be slow from this species
that contains two strong electron donors and two strong
π-acceptors. Thus, we sought ruthenium catalysts that
would not be converted to carbonyl compounds.
from the ruthenium alkoxide would then furnish the
ketone or aldehyde and the starting ruthenium dihy-
dride.
The reaction of 1,4-butanediol at 205 °C in the
presence of RuH2(PMe3)4 as catalyst generated several
ruthenium complexes. The isolation of these intermedi-
ates was complicated by the presence of neat, high-
boiling γ-butyrolactone. We were unable to obtain these
complexes as solids by precipitation from the solvent
and were unable to isolate any of them in pure form
after evaporation of the lactone at elevated tempera-
tures.
To obtain a less soluble and more crystalline product,
we conducted the dehydrogenative cyclization of 1,2-
benzenedimethanol in toluene at 130 °C with 13 mol %
RuH2(PMe3)4. After 10 h, a major complex was formed,
and this complex was also present in the cyclization
reaction of 1,4-butanediol catalyzed by RuH2(PMe3)4, as
judged by comparison of 31P NMR chemical shifts.
Because 1,2-benzenedimethanol and the phthalide prod-
uct of cyclization are solids, we were able to separate
the major species from the reactant and product as a
colorless oil by repeated extractions of the reaction
solution with pentane. This oil was identified as cis,-
mer-RuH2(CO)(PMe3)3 (7) by comparison of the 1H, 13C,
and 31P NMR spectra of the isolated species with those
of an authentic sample.19 cis,mer-RuH2(CO)(PMe3)3 (7)
was prepared independently by bubbling of CO through
a solution of mer-RuH(η2-Η2ΒΗ2)(PMe3)3 in pentane.
An Approach without Alkoxide Decomposi-
tion: Dehydrogenation by the Outer-Sphere Bi-
functional Mechanism. To avoid the generation of
(19) Kohlmann, W.; Werner, H. Z. Naturforsch. (B) 1993, 48, 1499-
1511.

2444 Organometallics, Vol. 24, No. 10, 2005
Zhao and Hartwig
Scheme 7
Scheme 8
Table 3. Three Catalysts that Exhibit High
Turnover Numbers
carbonyl ligands by â-hydrogen elimination of alkoxides
and activation of the resulting aldehydes, we sought
catalysts for the dehydrogenative cyclization that would
react by a pathway without alkoxide ligands and that
would be less likely to add aldehyde C-H bonds.
Complexes that react through the metal-ligand bifunc-
tional mechanism could catalyze the dehydrogenation
without an acceptor and without generation of carbonyl
ligands (Scheme 7).
entry
catalyst
time (h)
TON
1
2
3
4
RuH2(PMe3)4 (1)
40
40
40
48
3780a
RuH2(CO)(PMe3)3 (7)
cis-(PMe3)2RuCl2(eda) (18)
cis-(PMe3)2RuCl2(eda) (18)
3170a
4360a
17 000b
a Reaction conditions: 0.014 mmol of catalyst and 61 mmol of
1,4-butanediol were heated at 205 °C under N2 for 40 h in an open
system. b Reaction conditions: 0.014 mmol of catalyst and 240
mmol of 1,4-butanediol were heated at 205 °C under N2 for 48 h
in an open system.
The proposed cycle for dehydrogenation involves two
intermediates and runs in the opposite direction of the
catalytic cycle for the hydrogenation of ketones. The NH
proton and the Ru hydride in complex A combine to form
molecular hydrogen and complex B. The amide nitrogen
and the metal center in complex B then combine with
the alcohol to form a six-membered transition state TS2
that generates ketone and the starting diamine complex.
Noyori et al. reported three routes to prepare the
bisphosphine diamine ruthenium hydrogenation cata-
lysts.11 Complexes 15 and 16 were synthesized in a
manner similar to the synthesis of (binap)RuCl2(DPEN)
(DPEN ) 1,2-diphenylethylenediamine) reported by
Noyori, which involved treatment of [RuCl2(diphosphine)-
(dmf)n] with 1.1 equiv of a diamine. Triphenylphosphine
complex 17, which was prepared to test the activity
versus complexes of alkylphosphines, was synthesized
according to a literature procedure from RuCl2(PPh3)3.
To prepare (PMe3)2RuCl2(eda) (18, eda ) ethylenedi-
amine), (COD)Ru(η3-2-methallyl)2 (COD ) 1,5-cyclooc-
tadiene) was treated with 2 equiv of PMe3 to generate
(PMe3)2Ru(η3-2-methallyl)2 (6a) in 77% isolated yield.
This complex was converted to cis-(PMe3)2RuCl2(eda)
(18) in 54% yield by the reaction of (PMe3)2Ru(η3-2-
methallyl)2 (6a) with 2 equiv of ethanolic HCl in acetone,
followed by reaction of the resulting material with 1
equiv of ethylenediamine (eda) in DMF at room tem-
perature for 1 h (Scheme 8).
Complexes 15, 16, and 17 exhibited good to excellent
activities without added base (Table 1). Although the
addition of base activates these compounds for hydro-
genation at low temperatures,9,24 addition of a base
inhibited the dehydrogenation reaction at high temper-
atures.
The complex cis-(PMe3)2RuCl2(eda) (18) was more
active than any catalyst reported previously for the
conversion of 1,4-butanediol to γ-butyrolactone. The
reaction of 5.5 g of 1,4-butanediol catalyzed by 0.014
mmol of catalyst 1, 7, and 18 at reflux (205 °C) for 40 h
generated γ-butyrolactone in 87% (TON: 3780), 73%
Catalytic Studies with Complexes that Operate
with an Outer-Sphere Mechanism. Results on the
conversion of 1,4-butanediol to γ-butyrolactone cata-
lyzed by complexes that are capable of reactivity through
an outer-sphere mechanism are summarized in Table
2. Preliminary experiments with CATHy complexes20
(8-11) as catalysts for the acceptorless dehydrogenation
of 1,4-butanediol to γ-butyrolactone generated little or
no γ-butyrolactone. The Shvo dimer21 (12), the amino
analogue of the Shvo amide22 (13), and trans-RuHCl-
(tmen)(BINAP)23 (14; tmen ) tetramethylethylenedi-
amine, BINAP ) 2,2′-bis(diphenylphosphino)-1,1′-bi-
naphthyl) with a diamine that lacks â-hydrogens were
also evaluated as catalysts for the conversion of 1,4-
butanediol to γ-butyrolactone. Each reacted with low to
moderate yields and slow rates (Table 1). We suspected
that the low activity of the amino analogue of Shvo’s
compound 13 and certain CATHy complexes for the
dehydrogenative cyclization results from their low
stability at the high temperatures required to drive the
reaction to completion.
We reasoned that the bisphosphine diamine com-
plexes related to those for asymmetric hydrogenation
developed by Ikariya and Noyori, but containing alkyl-
phosphine ligands, might be able to catalyze the dehy-
drogenation more efficiently. As noted above, complexes
with alkylphosphines usually exhibit better stability at
high temperature than complexes of arylphosphines. In
addition, complexes with a combination of phosphine
and diamine ligands have been shown to catalyze
hydrogenation through an outer-sphere mechanism.
Thus, we set out to synthesize a series of simple
bisalkylphosphine diamine complexes (15-18).
(20) Murata, K.; Ikariya, T. J. Org. Chem. 1999, 64, 2186-2187.
(21) Persson, B. A.; Larsson, A. L. E.; Le Ray, M.; Backvall, J. E. J.
Am. Chem. Soc. 1999, 121, 1645-1650.
(22) Choi, J. H.; Kim, Y. H.; Nam, S. H.; Shin, S. T.; Kim, M. J.;
Park, J. Angew. Chem., Int. Ed. 2002, 41, 2373-2376.
(23) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H. J. Am.
Chem. Soc. 2001, 123, 7473-7474.
(24) Ohkuma, T.; Koizumi, M.; Muniz, K.; Hilt, G.; Kabuto, C.;
Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508-6509.

Ru-Catalyzed Dehydrogenative Cyclization of Diols
Organometallics, Vol. 24, No. 10, 2005 2445
amide analogue,22 RuCl2(CO)(PMe3)3, and RuCl2(CO)2(PMe3)2
were prepared by literature procedures.
32
(TON: 3170), and 100% (TON: 4360) yield, respectively.
Furthermore, the reaction of 22 g of 1,4-butanediol
catalyzed by 5.4 mg (0.0058 mol %) of cis-(PMe3)2RuCl2-
(eda) (18) at reflux (205 °C) for 48 h generated γ-buty-
rolactone in 100% yield. This yield corresponds to a
turnover number of 17 000. This turnover number
constitutes a commercially viable method to generate
γ-butyrolactone from the commodity material 1,4-bu-
tanediol.
1,2-Bis(dimethylphosphino)ethane (Strem), ethylenediamine
(Aldrich), 1,4-butanediol (Aldrich), and (COD)Ru(η3-(CH2)2-
CHCH3)2 (COD ) 1,5-cyclooctadiene) (Acros) were used as
received without further purification. Hydrogen (zero grade)
was obtained from Airgas. 1,3-Propanediol and 1,4-butanediol
were purchased from Aldrich and degassed prior to use. All
other chemicals were used as received from commercial
suppliers.
Representative Procedure for the Dehydrogention of
1,4-Butanediol at 205 °C on a Small Scale. In a drybox,
the ruthenium catalyst (0.0057 mmol) was suspended in 0.10
mL (1.1 mmol) of 1,4-butanediol in a screw-capped vial. The
reaction mixture was stirred at 205 °C for 12 h. The vial was
allowed to cool to room temperature. A small amount (15.0
mg) of the reaction mixture and naphthalene (1.8 mg, 0.0491
mmol) were weighed and dissolved in dichloromethane, and
an aliquot was removed and analyzed by GC.
General Procedure for the Dehydrogention of 1,4-
Butanediol at 205 °C on a 60 mmol Scale. In a drybox, the
ruthenium catalyst (0.014 mmol) was suspended in 5.5 g or
in 22 mL of 1,4-butanediol (61 or 240 mmol) in a 25 or 100
mL round-bottom flask. The reaction mixture was stirred at
205 °C for 48 h under nitrogen. The resulting product was
analyzed by GC.
Conclusion
Through catalyst design and identification of potential
pathways for catalyst degradation, we have identified
several Ru complexes that are highly reactive and
thermally stable as catalysts for the dehydrogenative
cyclization of 1,4-butanediol to γ-butyrolactone without
hydrogen acceptor or solvent. An alkylphosphine ana-
logue of Noyori’s catalysts for alcohol dehydrogenation
catalyzed the acceptorless dehydrogenation of 1,4-bu-
tanediol to γ-butyrolactone with high selectivity and
high turnover numbers. This route to γ-butyrolactone
eliminates the need for stoichiometric amount of oxi-
dant, lacks solvent, and uses a reagents1,4-butanediols
formed from butadiene, acetic acid, and hydrogen.1
Synthesis of (PMe3)2Ru(η3-(CH2)2CHCH3)2 (6a). To a
pentane suspension of (COD)Ru(η3-(CH2)2CHCH3)2 (150 mg,
0.470 mmol) was added 1 mL of a 1.0 M solution of PMe3 in
toluene (1.0 mmol). The suspension was heated at 80 °C for 5
h. Evaporation of the solvent in vacuo yielded the title complex
(132 mg, 0.363 mmol, 77%) as a yellow solid. 1H NMR (400
MHz, C6D6): δ 0.69 (d, J ) 13.6 Hz, 2H), 0.98 (d, J ) 13.6 Hz,
18H), 1.23 (d, J ) 15.2 Hz, 2H), 1.35 (br, 2H), 2.10 (d of t, J )
3.2 Hz, 2H), 2.15 (s, 6H). 31P{1H} NMR (202.4 MHz, C6D6): δ
6.47. 13C{1H} NMR (100.6 MHz, C6D6): δ 19.79 (t, J ) 13.4
Hz), 20.04 (t, J ) 14.1 Hz), 27.13 (s), 37.79 (t, J ) 5.0 Hz),
44.25 (quin, J ) 10.2 Hz), 92.47(s). Anal. Calcd for C14H32P2-
Ru: C, 46.27; H, 8.88. Found: C, 46.13; H, 8.80.
Experimental Section
General Procedures. Unless otherwise noted, all reac-
tions, recrystallizations, and routine manipulations were
performed at ambient temperature in an argon-filled glovebox
or by using standard Schlenk techniques. Pentane, benzene,
toluene, tetrahydrofuran, and diethyl ether were dried by
passage through solvent purification columns (Innovative
Technology, MA).25 Deuterated solvents for use in NMR
experiments were obtained from Cambridge Isotope Labora-
tories (CIL) and were stored under static vacuum over purple
sodium benzophenone ketyl and were vacuum transferred
before use. Acetone was dried over CaSO4 and was vacuum
transferred. Chloroform was dried over P2O5 and was vacuum
transferred. CD2Cl2 was dried over CaH2 and was vacuum
transferred.
Synthesis of (DMPE)Ru(η3-(CH2)2CHCH3)2 (6b). (COD)-
Ru(η3-(CH2)2CHCH3)2 (150 mg, 0.47 mmol) and 1,2-bis(dim-
ethylphosphino)ethane (80 mg, 0.53 mmol) were dissolved in
pentane (2 mL), and the suspension was heated at 80 °C for 5
h. The solution was filtered, and the solvent was evaporated
in vacuo. The resulting solid was recrystallized in pentane at
-35 °C to give a colorless solid (50 mg, 0.138 mmol, 29%). 1H
NMR (400 MHz, C6D6): δ 0.57 (d, J ) 7.2 Hz, 6H), 0.78 (d, J
) 15.6 Hz, 2H), 1.04 (d, J ) 7.2 Hz, 2H), 1.151-1.255 (m, 4H),
1.28 (d, J ) 8.4 Hz, 6H), 1.46 (s, 2H), 2.12 (q, J ) 2.8 Hz, 2H),
2.20 (s, 6H). 31P{1H} NMR (400 MHz, C6D6): δ 48.75. 13C{1H}
NMR (100.6 MHz, C6D6): δ 10.17 (m), 22.60 (d of t, J1 ) 25.6
Hz, J2 ) 9.0 Hz), 27.08 (s), 31.29 (d of d, J1 ) 23.7 Hz, J2 )
22.3 Hz), 34.22 (t, J ) 4.1 Hz), 39.92 (d of t, J1 ) 20.1 Hz, J2
) 13.2 Hz), 94.20 (s). Anal. Calcd for C14H30P2Ru: C, 46.53;
H, 8.37. Found: C, 46.42; H, 8.29.
1H NMR spectra were obtained at 400 or 500 MHz. 13C{1H}
NMR spectra were obtained at 100.6 or 125.8 MHz. 31P{1H}
NMR spectra were obtained at 162, 122, or 202 MHz. 1H, 13C,
and 2H NMR chemical shifts are reported in parts per million
downfield from tetramethylsilane and were referenced to
residual protiated (1H) or deuterated solvent (13C) or natural
abundance deuterated solvent (2H). 31P NMR chemical shifts
were referenced to an external sample of 85% H3PO4. GC
analyses were performed using a DB-1301 narrow bore
column. Response factors were calculated from the ratios of
1
pure product to added naphthalene in H NMR spectra and
GC traces.
Synthesis of RuCl2(PMe3)2(eda) (18). Into a 20 mL vial
was placed (PMe3)2Ru(η3-(CH2)2CHCH3)2 (200 mg, 0.55 mmol).
Acetone (5 mL) and HCl in ethanol (1 M, 1.3 mL) were added,
and the mixture was stirred at room temperature for 2 h. The
resulting orange solution was evaporated under vacuum.
Degassed DMF (6 mL) and ethylenediamine (100 µL, 1.50
mmol, 2.7 equiv) were added to the residue, and the resulting
solution was stirred at room temperature for 3 h. The solvent
was removed in vacuo, and the solid was crystallized by
layering the concentrated toluene solution with pentane at -35
Materials. The reagents RuH2(PMe3)4,26 (bisphosphine)Ru-
(2-methylallyl)2 complexes,27 trans-RuHCl(tmen)(BINAP) (tmen
) tetramethylethylenediamine),23 RuH2(PPh3)4,28 RuH2(PEt3)4,29
RuH2(PBu3)4,30 RuH2(DMPE)2 (DMPE ) 1,2-bis(dimethyleth-
ylphosphino)ethane),31 CATHy catalysts,20 Shvo dimer,21 Shvo
(25) Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.;
Timmers, F. J. Organometallics 1996, 15, 1518-1520.
(26) Hartwig, J. F.; Andersen, R. A.; Bergman, R. G. J. Am. Chem.
Soc. 1991, 113, 6492-6498.
(27) Genet, J. P.; Pinel, C.; Ratovelomananavidal, V.; Mallart, S.;
Pfister, X.; Deandrade, M. C. C.; Laffitte, J. A. Tetrahedron: Asym-
metry 1994, 5, 665.
(30) Mitsudo, T.; Nakagawa, Y.; Watanabe, K.; Hori, Y.; Misawa,
H.; Watanabe, H.; Watanabe, Y. J. Org. Chem. 1985, 50, 565-571.
(31) Field, L. D.; Hambley, T. W.; Yau, B. C. K. Inorg. Chem. 1994,
33, 2009-2017.
(32) Krassowski, D. W.; Nelson, J. H.; Brower, K. R.; Hauenstein,
D.; Jacobson, R. A. Inorg. Chem. 1988, 27, 4294-4307.
(28) Levison, J. J.; Robinson, S. D. J. Chem. Soc. (A) 1970, 2947-
2954.
(29) Gusev, D. G.; Hubener, R.; Burger, P.; Orama, O.; Berke, H. J.
Am. Chem. Soc. 1997, 119, 3716-3731.

2446 Organometallics, Vol. 24, No. 10, 2005
Zhao and Hartwig
1
°C (115 mg, 0.300 mmol, 54%). H NMR (400 MHz, C6D6): δ
[RuCl2(C6H6)]2 (129 mg, 0.258 mmol) and DIOP (273 mg, 0.55
mmol). This material was suspended in 10 mL of degassed
DMF, and the resulting solution was stirred under argon at
100 °C for 10 min. The solution turned reddish brown. After
the solution was cooled to room temperature, ethylenediamine
(40 µL, 0.60 mmol) was added, and the mixture was stirred
for 1 h. The solvent was evaporated in vacuo. The residue was
dissolved in 5 mL of CH2Cl2, and the resulting turbid solution
was filtered through Celite. The filtrate was concentrated to
about 1 mL. Upon addition of ether, a yellow powder was
obtained. The supernatant was removed by pipet, and the
resulting yellow solid was dried under reduced pressure to give
15 (297 mg, 0.41 mmol, 79% yield). Too many aliphatic
protons: 1H NMR (400 MHz, C6D6): δ 1.40 (s, 6H), 2.00 (d, J
) 4.0 Hz, 4H), 2.45 (br, 2H), 2.60 (br, 2H), 3.30-3.38 (m, 4H),
4.66 (s, 2H), 7.00 (m, 12H), 7.72-7.75 (m, 4H), 7.82-7.87 (m,
4H). 31P{1H} NMR (202.4 MHz, C6D6): δ 37.92 (s). 13C{1H}
NMR (100.6 MHz, C6D6): δ 27.35 (s), 32.92 (t, J ) 14.7 Hz),
43.07 (s) 78.02 (t, J ) 6.3 Hz), 107.61 (s), 128.10 (t, J ) 4.3
Hz), 128.14 (t, J ) 4.3 Hz), 128.95 (s) 129.35 (s) 132.57 (t, J )
4.3 Hz), 133.91 (t, J ) 5.0 Hz), 138.20 (t, J ) 18.2 Hz), 139.59
(t, J ) 19.3 Hz). Anal. Calcd for C33H40Cl2N2O2P2Ru: C, 54.25;
H, 5.52; N, 3.83. Found: C, 54.11; H, 5.34; N, 3.93.
1.27 (t, J ) 4.0 Hz, 18H), 2.25 (s, 4H, 2CH2), 2.57 (s, 4H, 2NH2).
31P{1H} NMR (202.4 MHz, C6D6): δ 21.01 (s). 13C{1H} NMR
(100.6 MHz, C6D6): δ 17.68 (t, J ) 13.5 Hz), 42.97 (s). Anal.
Calcd for C8H26P2Cl2N2Ru: C, 25.01; H, 6.82; N, 7.29. Found:
C, 24.96; H, 6.77; N, 7.20.
Synthesis of (DPPF)RuCl2(eda) (14). Into a 20 mL
scintillation vial equipped with a magnetic stir bar was placed
[RuCl2(C6H6)]2 (129 mg, 0.258 mmol) and DPPF (305 mg, 0.55
mmol). This material was suspended in 10 mL of degassed
DMF and stirred under argon at 100 °C for 10 min to form a
reddish brown solution. After the solution was cooled to room
temperature, ethylenediamine (40 µL, 0.60 mmol) was added,
and the mixture was stirred for 1 h. The solvent was
evaporated in vacuo. The residue was dissolved in 5 mL of CH2-
Cl2, and the turbid solution was filtered through Celite. The
filtrate was concentrated to about 1 mL, and upon addition of
ether a yellow powder was obtained. The supernatant was
removed by pipet, and the resulting yellow solid was dried
under reduced pressure to give 14 (274 mg, 0.35 mmol, 68%
yield). 1H NMR (400 MHz, CD2Cl2): δ 2.66 (s, 4H), 2.71 (s,
4H), 4.20 (s, 4H), 4.63 (s, 4H), 7.27-7.37 (m, 12H), 7.78-7.82
(m, 8H). 31P{1H} NMR (121.6 MHz, C6D6): δ 49.06 (s). 13C-
{1H} NMR (100.6 MHz, CD2Cl2): δ 43.53 (s) 70.33 (t, J ) 2.5
Hz), 76.49 (t, J ) 3.4 Hz), 87.59 (t, J ) 24.7 Hz), 127.55 (t, J
) 4.2 Hz), 129.25 (s) 134.64 (t, J ) 5.1 Hz), 139.29 (t, J ) 18.5
Hz). Anal. Calcd for C36H36Cl2FeN2P2Ru: C, 54.98; H, 4.61;
N, 3.56. Found: C, 54.83; H, 4.74; N, 3.70.
Acknowledgment. We thank the DOE and Mitsub-
ishi Chemicals for support of this work.
Synthesis of (DIOP)RuCl2(eda) (15). Into a 20 mL
scintillation vial equipped with a magnetic stir bar were placed
OM048983M