Chiral pyranoside phosphite-oxazolines: A new class of ligand for asymmetric catalytic hydrogenation of alkenes

Article abstract of DOI:10.1021/ja801706s

We have described the first successful application of a phosphite-oxazoline ligand library in the asymmetric Ir-catalyzed hydrogenation of several unfunctionalized olefins. The introduction of a bulky biaryl phosphite moiety in the ligand design is highly adventitious in the product outcome. By carefully selecting the ligand components, we obtained high activities (TOFs up to >1500 mol·(mol·h)^-1 at 1 bar of H₂) and enantioselectivities (ee values up to >99%) and, at the same time, show a broad scope for different substrate types. So, this is an exceptional ligand class that competes favorably with a few other ligand series that also provide high ee values for tri- and disubstituted substrate types. Copyright

Full text of DOI:10.1021/ja801706s

Published on Web 05/16/2008
Chiral Pyranoside Phosphite-Oxazolines: A New Class of Ligand for
Asymmetric Catalytic Hydrogenation of Alkenes
Montserrat Die´guez,*,† Javier Mazuela,† Oscar Pa`mies,† J. Johan Verendel,‡ and
Pher G. Andersson*,‡
Departament de Qu´ımica F´ısica i Inorga`nica, UniVersitat RoVira i Virgili, Campus Sescelades, C/ Marcel ·l´ı
Domingo, s/n 43007 Tarragona, Spain, and Department of Biochemistry and Organic Chemistry, Uppsala
UniVersity, BOX 576, 751 23 Uppsala, Sweden
Received March 7, 2008; E-mail: montserrat.dieguez@urv.cat; pher.andersson@kemi.uu.se
The enantioselective hydrogenation of olefins is one of the most
powerful transformations in asymmetric catalysis for preparing
optically active compounds. Although ruthenium- and rhodium-
catalyzed asymmetric hydrogenation of chelating olefins has a long
history, unfunctionalized olefins are still a challenge, because they
lack an adjacent polar group.1 Iridium complexes with chiral P,N
Figure 1. Privileged P,N ligands for Ir-catalyzed hydrogenation of
alkenes.
ligands have become established as efficient catalysts for the
hydrogenation of unfunctionalized olefins.2 In this context, Pflatz
and others have used phosphine-oxazoline ligands as chiral mimics
of Crabtree’s catalyst. They have been successfully used for the
asymmetric hydrogenation of a limited range of alkenes.3 Recently,
the composition of the ligands has been extended by replacing the
phosphine moiety with a phosphinite or a carbene group and the
oxazoline moiety with other N-donor groups (such as pyridine,
thiazole, and oxazole). The structure of the chiral ligand’s backbone
has also been modified.4 These modifications have led to the
discovery of three main ligand structures: phosphinite-oxazoline
1,4b,g phosphinite-oxazole 2,4d and phosphinite-pyridine 3,4c
which have considerably broadened the scope of Ir-catalyzed
hydrogenation.
Figure 2. Phosphite-oxazoline ligands L1-L4a-f and phosphinite-
oxazoline ligand L1h.
Table 1. Ir-Catalyzed Asymmetric Hydrogenation of S1 Using
Ligands L1-L4a-ha
In the past few years, a group of less electron-rich phosphorus
compounds, phosphite containing ligands, have demonstrated their
huge potential utility in many transition-metal catalyzed reactions.5
Their highly modular construction, facile synthesis from readily
available chiral alcohols and greater resistance to oxidation than
phosphines have proved to be highly advantageous. Despite the
successful early use of phosphite ligands in the Rh-catalyzed
hydrogenation of dehydroaminoacid derivatives,6 only one report
has been published on phosphite ligands, TADDOL-based phos-
phite-oxazoline ligands, in the Ir-catalyzed hydrogenation of
alkenes.7 However, their substrate range limitation was higher and
enantioselectivities and activities lower than their related phos-
phinite/phosphine-oxazoline ligands. They also required higher
catalyst loadings (4 mol %) and higher pressures (100 bar) to
achieve full conversions. More research is therefore needed to study
the possibilities of phosphite-oxazoline ligands in this process. In
thisCommunicationwepresenttheapplicationofaphosphite-oxazoline
ligand library (L1-L4a–g, Figures 1,2)8 in the asymmetric Ir-
catalyzed hydrogenation of several unfunctionalized olefins. For
comparative purposes, we also evaluated phosphinite-oxazoline
analogue L1h. These ligands are derived from natural D-glu-
cosamine so they also have the advantages of carbohydrates: that
is to say, they are cheap and can be easily constructed in modules.
With this library we therefore investigated the effects of systemati-
cally varying the electronic and steric properties of the oxazoline
substituents (L1-L4) and different substituents/configurations in
the biaryl phosphite moiety (a-g). By carefully selecting these
entry
L
mol % Ir
% conversionb
% eec
1
2
3
4
5
6
7
8
L1a
L1b
L1c
L1d
L1e
L1f
L2a
L3a
L4a
L1c
L1h
2
2
2
2
2
2
2
2
100
100
100
50
45
100
98
99 (R)
98 (R)
>99 (R)
20 (R)
98 (R)
99 (R)
95 (R)
99 (R)
92 (R)
>99 (R)
95 (R)
40
9
10
11
2
0.2
2
100
100
100
a Reactions carried out using 1 mmol of S1. b Conversion measured
by 1H NMR. c Enantiomeric excesses determined by chiral HPLC.
elements, we achieved high enantioselectivities and activities in a
wide range of substrates.
In the first set of experiments, we used the Ir-catalyzed
hydrogenation of trans-R-methylstilbene S1 to scope the potential
of ligands L1-L4a-g. The results are summarized in Table 1.
The reaction proceeded smoothly at room temperature. The catalyst
precursors [Ir(cod)(L)]BArF (L) L1-L4a–h) were prepared with a
standard protocol3d and used without further purification. The results
indicate that enantioselectivity is affected by the electronic and steric
properties of the substituents at the oxazoline moiety and by the
substituents/configuration in the biaryl phosphite moiety. However,
† Universitat Rovira i Virgili.
‡ Uppsala University.
9
7208 J. AM. CHEM. SOC. 2008, 130, 7208–7209
10.1021/ja801706s CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
natural chiral feedstock. In addition, they can be easily tuned in
the oxazoline and biaryl phosphite moieties so that their effect on
catalytic performance can be explored. By carefully selecting the
ligand components, we obtained high activities and enantioselectivities
under unoptimized reaction conditions. Of particular note are the
excellent activities and enantioslectivities at low catalyst loadings
obtained with simple disubstitued olefins. So, this is an exceptional
ligand family that competes favorably with a few other ligand series
that also provide high ee values for tri- and disubstituted substrate types.
The introduction of a bulky biaryl phosphite moiety in the ligand design
is highly advantageous in the product outcome. Therefore, these ligands
provides higher enantioselectivities than its phosphinite-oxazoline
analogue. These results provide a new class of ligands for the highly
active and enantioselective Ir-catalyzed hydrogenation of a wide range
of substrates. Mechanistic studies are currently under way and further
applications are being looked into.
Figure 3. Selected hydrogenation results. Reaction conditions: 0.2 mol %
catalyst, CH2Cl2 as solvent, 50 bar H2, 2 h. Reaction run with 1 mol %
catalyst.
a
Acknowledgment. We thank the Spanish (CTQ2007-62288/
BQU) and Catalan (2006BE-210167 and Distinction to M.D.)
Government, COST D40, Vetenskapsrådet (VR), and Astra Zeneca
for support. We are grateful to Pa¨ivi Kaukoranta for assistance with
chiral analyses.
Figure 4. Selected hydrogenation results. Reaction conditions: 0.2 mol%
catalyst, CH2Cl2 as solvent, 1 bar H2, 30 min.
activity is mainly affected by the steric properties of the oxazoline
substitutent and by the substituents at the ortho positions of the
biaryl phosphite moiety. The presence of bulky substitutents in the
biaryl phosphite and less-sterically demanding substituents in the
oxazoline is necessary if activities are to be high. The best result
(100% conversion; >99% ee) was therefore obtained with ligand
L1c (entry 3), which contains the optimal combination of the
substituent in the oxazoline and in the biaryl phosphite moieties.
We also performed the reaction at low catalyst loading (0.2 mol
%) using ligand L1c (entry 10). The excellent enantioselectivity
(>99% (R) ee) and activity (100% conversion after 2 h at room
temperature) were maintained.
Supporting Information Available: Experimental procedures and
characterization of new ligands L1f and L1g and [Ir(cod)(L)]BArF (L)
L1-L4a-h) complexes. This material is available free of charge via
the Internet at http://pubs.acs.org.
References
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Catalysis on Industrial Scale; Wiley: New York, 2004. (d) Brown, J. M.
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(2) For recent reviews, see: (a) Ka¨llstro¨m, K.; Munslow, I.; Andersson, P. G.
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(3) See for instance: (a) Tang, W.; Wang, W.; Zhang, X. Angew. Chem., Int.
Ed. 2003, 42, 943. (b) Hou, D.-R.; Reibenspies, J.; Colacot, T. J.; Burgess,
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Interestingly, these phosphite-oxazoline ligands showed higher
enantioselectivities than its corresponding phosphinite-oxazoline
analogue L1h (entry 3 vs 11) .
To study the potential of these readily available ligands further,
we also tested them in the asymmetric hydrogenation of several
trisubstituted unfunctionalized olefins S2-S4 (Figure 3). The
enantioselectivities are among the best observed for these substrates.2,9
It should be noted that if ligands are appropriately tuned, high
enantioselecitvities can also be obtained for the more demanding
Z isomer S4, which usually reacts with a lower enantioselectivity
than that of the corresponding E-isomer S3. Ir-L1c also proved to
be an excellent catalyst for the hydrogenation of R,ꢀ-unsaturated
ester S5, allylic alcohol S6, and acetate S7 (Figure 3).
Encouraged by the excellent results, we also tested the Ir-L1c
catalyst in the asymmetric hydrogenation of more demanding
substrates: the terminal olefins S8-S10 (Figure 4). For these
substrates, the development of highly enantioselective Ir-catalysts
is still a challenge. Therefore few catalytic systems have provided
high enantioselectivities.10 The enantiomeric excesses obtained for
this substrate class surpass the best values reported to date. Note
also the high activities obtained at low catalyst loadings (0.2 mol
%) under mild reaction conditions (1 bar of H2). Interestingly, Ir-
L1c is also capable of hydrogenating substrate S10, which contains
(5) For some representative examples see: (a) Claver, C.; Die´guez, M.; Pa`mies,
O.; Castillo´n, S. Catalytic Carbonylation Reactions; Beller, M.; Ed.;
Springer-Verlag: Berlin, 2006; pp 35-64. (b) Die´guez, M.; Pa`mies, O.;
Ruiz, A.; Claver, C. In Methodologies in Asymmetric Catalysis; Malhotra,
S. V.; Ed.; ACS: Washington, DC, 2004; pp 161-174. (c) Yan, M.; Zhou,
Z.-Y.; Chan, A. S. C. Chem. Commun. 2000, 115. (d) Pa`mies, O.; Die´guez,
M.; Claver, C. J. Am. Chem. Soc. 2005, 127, 3646. (e) Mata, Y.; Pa`mies,
O.; Die´guez, M. Chem.sEur. J. 2007, 13, 3296.
(6) See for instance: (a) Reetz, M. T.; Neugebauer, T. Angew. Chem., Int. Ed.
1999, 38, 179. (b) Die´guez, M.; Ruiz, A.; Claver, C. Chem. Commun. 2001,
2702.
(7) Hilgraf, R.; Pfaltz, A. AdV. Synth. Catal. 2005, 347, 61.
(8) Ligands L1-L4a-e have been successfully used in Pd-catalyzed allylic
substitution and Heck reactions, see: (a)(a) Mata, Y.; Die´guez, M.; Pa`mies,
O.; Claver, C. AdV. Synth. Catal. 2005, 347, 1943. (b) Reference 5e.
(9) The best enantioselectivities obtained so far are: >99% ee for S3 (ref 4c),
98% ee for S4(ref 4c), 99% ee for S5 (ref 3g), 98% ee for S6 (ref 4d) and
99% ee for S7 (ref 4d) at 1 mol % Ir-catalyst.
(10) For successful applications, see: (a) McIntyre, S.; Ho¨rmann, E.; Menges,
F.; Smidt, S. P; Pfaltz, A. AdV. Synth. Catal. 2005, 347, 282. (ee values up
to 94% for S9). (b) Reference 4d (ee values up to 97% for S9).
t
an sterically hindered Bu group, in high activities and enantiose-
lectivities.
In summary, we have described the first successful application
of phosphite containing ligands in the Ir-catalyzed asymmetric
hydrogenation of several unfunctionalized olefins. The advantage
of these phosphite-oxazoline ligands is that they are easily prepared
in a few steps from commercial D-glucosamine, an inexpensive
JA801706S
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