Phosphine-phosphite, a new class of auxiliaries in highly active and enantioselective hydrogenation

Article abstract of DOI:10.1039/b007850f

Excellent enantioselectivities (ee > 99%) and good activities (TOF > 1200 h^-1) are achieved under mild reaction conditions in the Rh-catalyzed hydrogenation of α,β-unsaturated carboxylic acid derivatives with the first family of phosphine-phosp

Full text of DOI:10.1039/b007850f

Phosphine–phosphite, a new class of auxiliaries in highly active and
enantioselective hydrogenation
Oscar Pàmies, Montserrat Diéguez, Gemma Net, Aurora Ruiz* and Carmen Claver
Departament de Química Física i Inorgànica, Universitat Rovira i Virgili, Pl. Imperial Tarraco 1, 43005 Tarragona,
Spain. E-mail: aruiz@quimica.urv.es
Received (in Cambridge, UK) 27th September 2000, Accepted 24th October 2000
First published as an Advance Article on the web
Excellent enantioselectivities (ee > 99%) and good activities
(TOF > 1200 h21) are achieved under mild reaction
conditions in the Rh-catalyzed hydrogenation of a,b-
unsaturated carboxylic acid derivatives with the first family
of phosphine–phosphite ligands containing a sugar back-
bone; these ligands are better than their diphosphine,
diphosphite and phosphinite analogues.
The new ligands 1a–d were synthesized very efficiently in
two steps from oxetane 2, as shown in Scheme 1. Compound 2
is easily prepared on a large scale from
-(+)-xylose.13 The key
D
step is the oxetane ring opening using a slight excess of
potassium diphenylphosphide in DMF to afford phosphine 3 in
80% yield after column chromatography.14 This step is a novel
strategy for easily synthesizing related ligands. Reacting 3 with
1 equivalent of the corresponding phosphorochloridite formed
in situ15 in the presence of base provided easy access to the
desired ligands 1a–d. These were isolated in good yields as air-
stable solids that are fairly robust towards hydrolysis. Selected
spectroscopic data are shown in Table 1.
The scope of asymmetric hydrogenation of alkenes has been
gradually extended both in reactant structure and catalyst
efficiency over many years.1 Chiral bidentate phosphorus
ligands have played a dominant role in the success of
asymmetric hydrogenation.1,2 The early excellent enantiose-
lectivities obtained with Binap3 and Dipamp4 promoted the
synthesis and application of a wide variety of new diph-
osphanes.2 Recent reports on the use of chiral diphosphite5 and
diphosphinite6 ligands in asymmetric hydrogenation have
demonstrated their potential utility. Nevertheless, the search for
new highly efficient ligand systems derived from readily
available simple starting materials is still of great importance.
Chiral auxiliaries from the chiral pool have attracted much
attention, making tedious optical resolution procedures un-
necessary. Carbohydrates are particularly advantageous be-
cause they are inexpensive compounds. Nevertheless, despite
the accessibility and the excellent enantioselectivities obtained
with sugar-derived ligands,5–7 their full potential in providing
chiral ligands has scarcely been exploited.2a In a previous paper,
different types of phosphorus ligands with a xylofuranoside
backbone have been applied to asymmetric hydrogenation with
varying degrees of success. Moderate enantioselectivities (up to
35%) with phosphine–phosphinite and diphosphinite ligands
have been reported by Brunner and Pieronczyk.8 More recently,
we reported moderate (up to 35%) and good (up to 91%)
enantiomeric excesses at room temperature with diphosphites9
and diphosphines,10 but in both cases the activities were low.
Continuing our interest in carbohydrates as an available
chiral source for preparing ligands and encouraged by the
success of diphosphine2 and diphosphite5 ligands, we have
designed a new family of chiral bidentate phosphine–phosphite
ligands 1 with a xylofuranoside backbone which combines the
advantages of both ligand types (Scheme 1). A feature of these
ligands is that they have two different phosphorus donor sites
than can a priori match the intermediates better, thus influenc-
ing their reactivity and achieving good enantioselectivity.11 We
also report their highly active and enantioselective rhodium
catalyzed asymmetric hydrogenation of a,b-unsaturated car-
boxylic acid derivatives. To the best of our knowledge this is the
first example of phosphine–phosphite ligands applied to
hydrogenation.12
Table 1 31P NMR spectroscopic data for ligands 1a–da
In a first set of experiments, we used the rhodium-catalyzed
hydrogenation of methyl N-acetamidoacrylate 4 to investigate
the potential of ligands 1a–d for asymmetric catalysis (Table
2).16 The reaction proceeded smoothly at 1 bar of H2 at room
temperature in CH2Cl2. Ligand 1a, with the achiral biphenyl
moiety at the phosphite, not only showed high asymmetric
induction (88.2%) but also very high catalytic activity (Table 2,
entry 1). The presence of bulky tert-butyl groups in the ortho-
positions of the biphenyl moiety (ligand 1b) have an extremely
positive effect on enantioselectivity (ee > 99%, Table 2, entry
2).17 Interestingly, the sense of the enantioselectivity is
reversed; the (S) enantiomer was obtained with ligand 1a and
the (R)-enantiomer was obtained with ligand 1b. Ligands 1c and
Scheme 1
DOI: 10.1039/b007850f
Chem. Commun., 2000, 2383–2384
This journal is © The Royal Society of Chemistry 2000
2383

Table 2 Asymmetric hydrogenation of methyl N-acetamidoacrylate 4 and
methyl (Z)-N-acetamidocinnamate 5 with [Rh(cod)2]BF4/1a
The combination of high enantioselectivities and high perform-
ances in simple unoptimized reactions and the low cost of the
ligands makes these catalyst systems very attractive for further
investigation. Moreover, these ligands were better than their
diphosphine and diphosphite counterparts. These results open
up a new class of ligands for asymmetric hydrogenation.
Research into other substrates and the use of these ligands in
other metal-catalyzed reactions is the subject of further
investigations.
We thank the Spanish Ministerio de Educación y Cultura and
the Generalitat de Catalunya (CIRIT) for their financial support
(PB97-0407-CO5-01) and for awarding a research grant (to
O. P.).
Notes and references
1 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994; Catalytic Asymmetric Synthesis, ed. I. Ojima, Wiley, New
York, 2000; Comprehensive Asymmetric Catalysis, ed. E. N. Jacobsen,
A. Pfaltz and H. Yamamoto, Springer, Berlin, 1999, vol. 1.
2 (a) H. Brunner and W. Zettlmeier, Handbook of Enantioselective
Catalysis, VCH, Weinheim, 1993; (b) A. Togni, C. Breutel, A.
Schnyder, F. Spindler, H. Landert and A. Tijani, J. Am. Chem. Soc.,
1994, 116, 4062; (c) U. Nettekoven, P. C. J. Kamer, P. W. N. M. van
Leeuwen, M. Widhalm, A. L. Spek and M. Lutz, J. Org. Chem., 1999,
64, 3996; (d) U. Barens, M. J. Burk, A. Gerlach and W. Hems, Angew.
Chem., Int. Ed., 2000, 39, 1981.
3 R. Noyori and H. Takaya, Acc. Chem. Res., 1990, 23, 345.
4 W. S. Knowles, M. J. Sabacky and B. D. Vineyard, J. Chem. Soc., Chem.
Commun., 1972, 10; B. D. Vineyard, W. S. Knowles, M. J. Sabacky,
G. L. Bachman and D. J. Weinkauff, J. Am. Chem. Soc., 1977, 99,
5946.
5 M. T. Reetz and T. Neugebauer, Angew. Chem., Int. Ed., 1999, 38,
179.
6 T. V. RajanBabu, T. A. Ayers and A. L. Casalnuovo, J. Am. Chem. Soc.,
1994, 116, 4101; T. A. Ayers and T. V. RajanBabu, in Process
Chemistry in the Pharmaceutical Industry, ed. K. G. Gadamasetti,
Marcel Dekker Inc., New York, 1999.
7 For recent representative examples see: K. Yonehara, T. Hashizyma,
K. Mori, K. Ohe and S. Uemura, Chem. Commun., 1999, 415; J.-C. Shi,
C.-H. Yueng, D.-X. Wu, Q.-T. Liu and B.-S. Kang, Organometallics,
1999, 18, 3796; M. Diéguez, O. Pàmies, A. Ruiz, S. Castillón and C.
Claver, Chem. Commun., 2000, 1607.
8 H. Brunner and W. Pieronczyk, J. Chem. Res. (S), 1980, 3, 76.
9 O. Pàmies, G. Net, A. Ruiz and C. Claver, Eur. J. Inorg. Chem., 2000,
1287.
1d containing a stereogenic binaphthyl moiety result in a high
reaction rate and a high enantioselectivity (Table 2, entries 3 and
4). Ligand 1c, which has an (S)-binaphthyl moiety, produces an
ee of 98.3% (S), while diastereomer 1d, which has an (R)-
binaphthyl moiety, produces an ee of 97.6% (R). Therefore, if
we compare the results with ligands 1a–d, we can assume that
the fast interchanging atropoisomers of ligand 1a predom-
inantly adopt the same configuration as that of 1c, while the
biphenyl moiety in ligand 1b predominantly adopts an (R)
configuration, probably due to the presence of the tert-butyl
group in the ortho-position. We can conclude that the sense of
the enantiodiscrimination is predominantly controlled by the
configuration of the biphenyl or the binaphthyl at the phosphite
moiety.
In general, the hydrogenation of 5 (Table 2, entries 5–8)
follows the same trend as for 4. However, the enantiomeric
excesses are somewhat lower and the reaction rate was slightly
slower. The configuration of the hydrogenated product is not
affected by the presence of the phenyl group in 5. The catalyst
precursor containing ligand 1b produced the highest enantio-
meric excess (98.8%; Table 2, entry 6).
10 O. Pàmies, G. Net, A. Ruiz and C. Claver, Eur. J. Inorg. Chem., 2000,
2011.
11 K. Inoguhi, S. Sakuraba and K. Achiwa, Synlett, 1992, 169.
12 Few phosphine–phosphite ligands have been described, although some
of them have been successfully applied in asymmetric hydroformyla-
tion. K. Nozaki, N. Sakai, T. Nanno, T. Higashijima, S. Mano, T.
Horiuchi and H. Takaya, J. Am. Chem. Soc., 1997, 119, 4413; S.
Deerenberg, P. C. J. Kamer and P. W. N. M. van Leeuwen,
Organometallics, 2000, 19, 2065.
13 Oxetane 2 was prepared by slightly modifying the procedure described:
P. Y. Goueth, M. A. Fauvin, M. Mashoudi, A. Ramiz, G. L. Ronco and
P. J. Villa, J. Nat., 1994, 6, 3.
It is remarkable that these phosphine–phosphite ligands
showed higher degrees of enantioselectivity and higher reaction
rates than their corresponding diphosphine 610 (Table 2, entry 9)
and diphosphite 79 (Table 2, entry 10) analogues under the same
reaction conditions.
14 Brunner et al. previously synthesized this phosphine in low yield (10%)
from the related monotosylated compound: H. Brunner and W.
Pieronczyk, J. Chem. Res. (S), 1980, 74; H. Brunner and W. Pieronczyk,
J. Chem. Res. (M), 1980, 1251.
15 Phosphorochloridites are easily prepared in one step from the corre-
sponding biphenol or binapthol as described: G. J. H. Buisman, P. C. J.
Kamer and P. W. N. M. van Leeuwen, Tetrahedron: Asymmetry, 1993,
4, 1625.
16 In a typical run, a Schlenk tube was filled with a dichloromethane
solution (6 mL) of substrate (1 mmol), [Rh(cod)2]BF4 (4.95 mg, 0.01
mmol) and ligand (0.011 mmol). This was then purged three times with
H2 and vacuum. The reaction mixture was then shaken under H2 (1 atm)
at 293 K. To remove the catalyst, the solution was placed on a short
silica gel column and eluted with CH2Cl2. Conversion and enantiomeric
excesses were determined by gas chromatography.
In summary, we have described the first application of
phosphine–phosphite ligands in asymmetric hydrogenation.
17 Detailed kinetic studies are under way.
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Chem. Commun., 2000, 2383–2384