Homogeneous hydrogenation of tri- and tetrasubstituted olefins: Comparison of iridium-phospinooxazoline [Ir-PHOX] complexes and crabtree catalysts with hexafluorophosphate (PF6) and tetrakis[3,5-bis(trifluoromethyl) phenyl]borate (BArF</su

Article abstract of DOI:10.1002/adsc.200700438

Four iridium complexes with achiral phosphino-oxazoline (PHOX) ligands were readily prepared in two steps starting from commercially available phenyloxazolines. The air-stable complexes with tetrakis[3,5- bis(trifluoromethyl)phenyl]borate (BAr_F

Full text of DOI:10.1002/adsc.200700438

FULL PAPERS
DOI: 10.1002/adsc.200700438
Homogeneous Hydrogenation of Tri- and Tetrasubstituted
Olefins: Comparison of Iridium-Phospinooxazoline [Ir-PHOX]
Complexes and Crabtree Catalysts with Hexafluorophosphate
(PF6) and Tetrakis
as Counterions
A
Bettina Wüstenberga,b and Andreas Pfaltza,*
a
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland
Fax : (+41)-61-267-1103; e-mail: andreas.pfaltz@unibas.ch
Current address: Research and Development, Research Center Chemical Process Technology, DSM Nutritional Products
b
Ltd., P.O. Box 3255, 4002 Basel, Switzerland
Received: September 3, 2007; Published online: December 14, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Four iridium complexes with achiral phos- [Ir(Py)ACTHERNGU(PCy3)ACHTREU(GN COD)]PF6, full conversion was ob-
phino-oxazoline (PHOX) ligands were readily pre- served. The productivity of the Crabtree catalyst
pared in two steps starting from commercially avail- could be strongly increased by replacing the hexa-
able phenyloxazolines. The air-stable complexes with fluorophosphate anion with tetrakis
tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF) methyl)phenyl]borate. In one case, in the hydrogena-
as counterion showed high reactivity in the hydroge- tion of a tetraalkyl-substituted C=C bond, [Ir(Py)-
nation of a range of tri- and tetrasubstituted olefins. (PCy3)(COD)]BArF gave higher conversion than cat-
ACHTRE[UNG 3,5-bis(trifluoro-
ACHTREUNG
A
ACHTREUNG
The best results were obtained with an iridium com- alyst 11. However, with several other substrates com-
plex (11) derived from a dicyclohexylphosphino-oxa- plex 11 proved to be superior.
zoline ligand bearing no additional substituents in
the oxazoline ring. With several substrates, which Keywords: Crabtree catalyst; homogeneous catalysis;
gave only low conversion with the Crabtree catalyst, hydrogenation; iridium; N,P ligands
Introduction
lyst deactivation strongly depends on the nature of
the counterion. Ir-PHOX complexes with the very
Homogeneous hydrogenation of tri- and tetrasubsti- weakly coordinating BArF anion {BArF =tetrakisACHTREUNG[3,5-
tuted alkenes is often difficult.[1] Most catalysts give bis(trifluoromethyl)phenyl]borate} proved to be much
only low or no conversion, unless a polar group, more resistant to deactivation and significantly less
which can speed up the reaction by coordination to moisture sensitive than the corresponding hexafluoro-
the catalyst, is present near the C=C bond. The Crab- phosphate salts.[3,4] Based on these findings, we
tree catalyst [Ir(Py)ACHTERUGN(PCy3)ACHTREU(GN COD)]PF6 (1) is a notable thought that simple achiral Ir-PHOX complexes as
exception, showing high activity in the hydrogenation well as the BArF analogue of the Crabtree catalyst
of unfunctionalized tri- and even tetrasubstituted al- would be synthetically useful catalysts, especially for
kenes.[2] However, with hindered alkenes conversion the hydrogenation of unreactive highly substituted
is often only moderate due to deactivation of the cat- olefins. Here we report the preparation of four achi-
alyst during the reaction.
ral, easily accessible Ir-PHOX complexes and a com-
In the course of our work on the asymmetric iridi- parative evaluation of these catalysts together with
um-catalyzed hydrogenation of olefins[3] we observed the Crabtree catalyst and its BArF analogue in the hy-
that iridium catalysts derived from phosphino-oxazo- drogenation of tri- and tetrasubstituted olefins.
line (PHOX) ligands in many cases gave higher con-
version than the Crabtree catalyst. The difference was
particularly striking for trisubstitued alkenes bearing
heteroaromatic substituents. We also found that cata-
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Homogeneous Hydrogenation of Tri- and Tetrasubstituted Olefins
FULL PAPERS
Results and Discussion
ortho-Lithiation of the commercially available oxazo-
lines 2 and 3 and subsequent reaction with diphenyl-
or dicyclohexylchlorophosphine provided the desired
phosphino-oxazolines 4–7 in high yields. Complexa-
tion of these ligands with [IrCAHTRE(UNG COD)Cl]2 followed by
[5]
anion exchange with NaBArF in a two-phase di-
chloromethane/water system led to the desired iridi-
um complexes 8–11 in 83–98% yield (Scheme 1).[6]
Scheme 2. Synthesis of iridium complex 13.
pressure for 2 h. For substrates 14–20 and 22 hydroge-
nation of the double bond occurs cleanly without for-
mation of by-products whereas for substrate 21 mix-
tures of mono- and bis-hydrogenated products were
observed. In this case the conversions listed in Table 1
refer to the formation of fully hydrogenated product.
Among the four Ir-PHOX derivatives 8–11, com-
plex 11 with a dicyclohexylphosphino group and no
additional substituents in the oxazoline ring proved to
be the most reactive catalyst, giving full conversion
with all substrates except 21 (Entry 8). Heterogeneous
catalysts such as palladium on charcoal also gave high
conversion with furan derivatives 14 and 15, but pro-
duced numerous by-products due to hydrogenation of
the furan and benzene rings. As can be seen from the
results, steric hindrance in the oxazoline ring reduces
the reactivity of the catalyst (compare 8 vs. 9 and 10
vs. 11), whereas an electron-rich dialkyl-substituted
Scheme 1. Synthesis of Ir-PHOX complexes 8–11.
To study the influence of the anion of the Crabtree phosphorus atom has a beneficial effect compared to
catalyst [Ir(Py)(PCy3)(COD)]PF6 (1), the analogous a diphenylphosphino group (11 vs. 9, 10 vs. 8).
BArF salt 13 was prepared.[7] Attempts to obtain com-
Comparison of the Crabtree catalyst (1) with the
A
ACHTREUNG
plex 13 directly from commercially available Crabtree BArF analogue 13 clearly shows the strong influence
catalyst by anion exchange were unsuccessful. There- of the counterion. In several cases, full conversion
fore, the route used by Crabtree[8] for the synthesis of was achieved with complex 13 whereas the Crabtree
the corresponding hexafluorophosphate 1 was chosen catalyst was deactivated before the reaction reached
(Scheme 2). By a modified procedure, starting from completion. The BArF anion also strongly reduces the
[IrACHTREUNG(COD)Cl]2, pyridine and NaBArF, the bisACHTREU(GN pyridine) oxygen and moisture sensitivity of the complex.
complex 12 was readily obtained. Stirring of complex While reactions with the hexafluorophosphate salt 1
12 in the presence of a slight excess of tricyclohexyl- had to be set up under inert atmosphere, the BArF an-
phosphine in methanol led to the desired product 13, alogue 13 and Ir-PHOX complexes 8–11 could be
which was isolated in 75% overall yield based on [Ir- handled in air. Overall, the BArF salt 13 is a more ef-
A
ficient catalyst than the corresponding hexafluoro-
Ir-PHOX complexes 8–11, the Crabtree catalyst (1) phosphate 1, although, in the hydrogenation of the
and the analogous BArF salt 13 were tested as cata- less reactive aromatic substrates 14, 18, 20, and 22, it
lysts in the hydrogenation of a range of tri- and tetra- suffers as well from deactivation. In these cases the
substituted olefins, including alkenes bearing furyl, Ir-PHOX catalyst 11 is clearly superior, especially for
thienyl and pyrrolyl groups (Table 1).[9] All reactions the very unreactive 1-pyrrolyl-2-phenylalkene 20 and
were carried out with 1 mol% iridium catalyst at the tetrasubstituted anisyl-alkene 22. Substrate 21
room temperature in CH2Cl2 under 50 bar hydrogen containing a tetra-alkyl substituted C=C bond is a no-
Adv. Synth. Catal. 2008, 350, 174 – 178
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Table 1. Ir-catalyzed hydrogenation of tri- and tetrasubstituted olefins with different Ir catalysts.
Entry
Substrates
Conversion [%]
8
9
10
11
1[b]
13
1[a]
2[a]
3[a]
4[a]
49
>99
>99
>99
>99
>99
>99
16
91
10
28
31
>99
>99
>99
>99
88
>99
31
>99
>99
>99
91
>99
5[a]
1
1
5
27
32
68
>99
>99
>99
2
6
6[a]
>99
>99
>99
7[c]
6
94
27
73
8[a,d]
17 (2.8:1 dr)
10 (2.3:1 dr)
41 (1.3:1 dr)
61 (2.6:1 dr)
>99
61 (6.0:1 dr)
>99 (4.0:1 dr)
9[a]
0
68
0
0
8
[a]
Conversions were determined by GC (Restek Rtx-1701).
Reactions using catalyst 1 were set up in a glove box under nitrogen atmosphere.
Conversions were determined by GC (Optima-5-Amin).
[b]
[c]
[d]
Conversion to the fully hydrogenated product. Diastereomeric ratios are given in brackets; the major isomer was the cis
compound according to published 13C NMR data (ref.[10]).
table exception. Here, the BArF analogue of the Crab- in two steps from commercially available starting ma-
tree catalyst was the only complex found that gave terials and is easy to handle due to its air and mois-
full conversion. With this substrate all catalysts react- ture stability. In several cases, this complex proved to
ed with moderate diastereoselectivity in favour of the be clearly superior to the Crabtree catalyst or hetero-
cis product.
geneous hydrogenation catalysts. In addition, we have
found that replacement of the hexafluorophosphate
anion of the Crabtree catalyst by BArF results in
higher catalytic activity and higher stability against
oxygen and moisture. The BArF analogue 13 proved
Conclusions
In summary, we have shown that the structurally to be a particularly efficient catalyst for the hydroge-
simple Ir-PHOX complex 11 is a highly efficient, con- nation of substrate 21 with a tetra-alkyl substituted
venient catalyst for the hydrogenation of tri- and tet- C=C bond. Our results indicate that complexes 11
rasubstituted olefins. The complex is readily prepared and 13 offer a practically useful alternative to the
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Homogeneous Hydrogenation of Tri- and Tetrasubstituted Olefins
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After evaporation of the solvents under reduced pressure a
red residue was obtained, which was purified by column
chromatography (see Supporting Information).
Crabtree catalyst for the hydrogenation of unreactive
olefins.
Synthesis of [Ir(Py)2CAHTRE(UNG COD)]BArF (12)
Experimental Section
[IrACHTER(UNG COD)Cl]2 (420 mg, 0.62 mmol) was dissolved in anhy-
Analytical data of compounds 4–13: see Supporting Infor-
mation
drous dichloromethane (20 mL) under argon atmosphere.
Upon dropwise addition of anhydrous pyridine (stored over
molecular sieves; 0.7 mL, 8.7 mmol) the red solution turned
yellow. Then NaBArF (1.20 g, 1.35 mmol) was added and the
reaction mixture was stirred at room temperature overnight.
After filtration under an argon atmosphere, the solvent and
the excess of pyridine were evaporated in high vacuum. The
yellow residue was dissolved in diethyl ether and filtered
twice, in order to remove residual NaBArF. The resulting
yellow solid was dried under high vacuum and used for the
synthesis of iridium complex 13 without further purification;
yield: 1.51 g (82%).
General Procedure for the Synthesis of PHOX
Ligands 4–7
Oxazoline 2 or 3 (2: 95 mg, 3: 80 mg, 0.54 mmol) was dis-
solved in anhydrous pentane (8 mL) under an argon atmos-
phere. Anhydrous N,N,N’,N’-tetramethylethylenediamine
(90 mL, 0.59 mmol) was added dropwise and the solution
was cooled using an acetone/dry ice cooling bath. At À788C
sec-butyllithium solution (1.3M in cyclohexane; 0.45 mL,
0.59 mmol) was added slowly via syringe. After stirring for
another 15 min, the cooling bath was removed, the orange
solution stirred at room temperature for 10 min and cooled
again to À788C. After 5 min chlorodiphenylphosphine
(0.11 mL, 0.70 mmol) or chlorodicyclohexylphosphine
(0.16 mL, 0.70 mmol), respectively, was added dropwise. The
yellow reaction mixture was warmed to room temperature
overnight and evaporated under high vacuum. The crude
products 4–6 were purified by column chromatography (see
Supporting Information); product 7 was used for the synthe-
sis of complex 11 without further purification.
Synthesis of [Ir(Py)ACHTREGU(N PCy3)ACHTREU(GN COD)]BArF (13)
[Ir(Py)2ACHTER(UNG COD)]BArF (12) (677 mg, 0.5 mmol) was trans-
ferred into a flame-dried 50-mL Schlenk flask in a glove box
and dissolved in degassed anhydrous methanol (20 mL). To
the resulting yellow solution tricyclohexylphosphine
(170 mg, 0.6 mmol) was added portionwise under an argon
atmosphere. The solution was stirred at room temperature
for 30 min and during this time an orange precipitate
formed. The solvent was removed under high vacuum and
the residue was precipitated from a mixture of anhydrous di-
ethyl ether (3 mL) and anhydrous pentane (30 mL), filtered
under argon atmosphere and dried under high vacuum. The
crude product was purified by crystallization from anhy-
drous diethyl ether; yield: 714 mg (92%).
General Procedure for the Synthesis of Ir-PHOX-
Complexes 8 and 9
Ligand 4 or 5 (4: 65 mg, 5: 61 mg, 0.18 mmol) was dissolved
in anhydrous dichloromethane (2 mL) under an argon at-
mosphere. To the stirred solution [IrACTHER(UNG COD)Cl]2 (61 mg,
Iridium-Catalyzed Hydrogenation
0.09 mmol) was added and the dark red solution was re-
fluxed for 2.5 h. After cooling to room temperature,
NaBArF (170 mg, 0.18 mmol) was added and the mixture
was stirred for another 10 min before dilution with water
(4 mL). After vigorous stirring for 30 min the layers were
separated and the aqueous layer was extracted twice with
dichloromethane (2”5 mL). The combined organic layers
were washed with water (5 mL) and dried over Na2SO4. The
solvent was evaporated under reduced pressure and the re-
sulting red solid purified by column chromatography (see
Supporting Information).
A glass-lined 60-mL autoclave equipped with a magnetic stir
bar was filled with substrate (0.1 mmol) and iridium catalyst
(1 mol%) dissolved in dichloromethane (0.5 mL). In case of
the BArF salts 8–11 and 13 the reaction was set up in air,
whereas with the Crabtree catalyst (1) the solution was pre-
pared in a glove box under a nitrogen atmosphere. The au-
toclave was pressurized to 50 bar with H2 and the solution
stirred at room temperature for 2 h. The pressure was re-
leased slowly and the solvent was evaporated. The residue
was taken up in hexanes (3 mL) and the mixture stirred for
another 10 min prior to filtration through a syringe filter
(Chromafil O-20/15 MS 0.2 mm, Macherey–Nagel). The fil-
trate was directly analyzed by GC to determine the conver-
sion. GC conditions: Carlo Erba HRGC Mega 2 Series
MFC 800; split-injector 1:20; FID-detector; sample amount:
1 mL; columns: a) Restek Rtx-1701, 14%-cyanopropylphen-
yl-86%-dimethylpolysiloxane (30 m, 0.25 mm, 0.25 mm); car-
rier gas: He (60 kPa); temperature program: 1008C (2 min),
78CminÀ1, 2508C (10 min) or b) Optima-5-Amin (30 m,
0.25 mm, 0.5 mm), carrier gas: He (100 kPa), temperature
program: 608C (3 min), 108CminÀ1, 2708C (15 min).
General Procedure for the Synthesis of Ir-PHOX-
Complexes 10 and 11
To a red solution of [IrACHTRE(UNG COD)Cl]2 (134 mg, 0.20 mmol) in
anhydrous dichloromethane (2 mL) under argon, a solution
of the appropriate ligand (6: 150 mg, 7: 137 mg, 0.40 mmol)
in anhydrous dichloromethane (10 mL) was added dropwise
over 15 min. After stirring the reaction mixture for 1 h at
room temperature, first NaBArF (189 mg, 0.20 mmol) and
10 min later water (10 mL) were added. The two layers were
stirred vigorously for 30 min. After separation of the layers,
the aqueous layer was extracted twice with dichloromethane
(10 mL). The combined red organic layers were washed with
water (10 mL) and brine (10 mL) and dried over Na2SO4.
Adv. Synth. Catal. 2008, 350, 174 – 178
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Bettina Wüstenberg and Andreas Pfaltz
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345, 33–43; S. J. Roseblade, A. Pfaltz, Acc. Chem. Res.
2007, 40, in press.
Acknowledgements
[4] S. P. Smidt, N. Zimmermann, M. Studer, A. Pfaltz,
We would like to thank Dr. Heinz Nadig for recording the
mass spectra and Werner Kirsch for elemental analyses. We
also thank Steve Nanchen for developing a procedure for the
Chem. Eur. J. 2004, 10, 4685–4693.
[5] a) R. Taube, S. J. Wache, J. Organomet. Chem. 1992,
428, 431–442; b) D. L. Reger, T. D. Wright, C. A.
Little, J. J. S. Lamba, M. D. Smith, Inorg. Chem. 2001,
40, 3810–3814; c) J. L. Leaser, Jr., R. Cvetovich, F.-R.
Tsay, U. Dolling, T. Vickery, D. Bachert, J. Org. Chem.
2003, 68, 3695–3698.
synthesis of iridiumcomplex
12. Financial support by the
Swiss National Science Foundation is gratefully acknowl-
edged.
[6] The hexafluorophosphate analogue of complex 8 has
been synthesized before by Nicole Zimmermann, see:
N. Zimmermann, Dissertation, University of Basel,
2001.
[7] Complex 13 has been reported but no experimental
procedures were given, R. Salter, I. Bosser, J. Label.
Compd. Radiopharm. 2003, 46, 489–498.
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