Synthesis of novel chiral monophosphine ligands derived from isomannide and isosorbide. Application to enantioselective hydrogenation of olefins

Article abstract of DOI:10.1016/j.tetlet.2012.07.035

A new class of monophosphine ligands has been prepared from natural chirality renewable source, 1,4:3,6-dianhydrohexitol compounds, via a nucleophilic substitution process, or a hydrophosphination reaction involving microwave activation. These ligands have been evaluated for the rhodium-catalyzed enantioselective hydrogenation of olefins giving good conversion and enantioselectivity up to 95% and 96% ee, respectively.

Full text of DOI:10.1016/j.tetlet.2012.07.035

Tetrahedron Letters 53 (2012) 4900–4902
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Tetrahedron Letters
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Synthesis of novel chiral monophosphine ligands derived from isomannide
and isosorbide. Application to enantioselective hydrogenation of olefins
Houssein Ibrahim a, Chloée Bournaud a, Régis Guillot b, Martial Toffano a, , Giang Vo-Thanh a,
⇑
⇑
a Institut de Chimie Moléculaire et des Matériaux d’Orsay, ICMMO, UMR 8182, Laboratoire de Catalyse Moléculaire, Université Paris-Sud 11, 91405 Orsay Cedex, France
b CNRS, Délégation Ile de France Sud, Orsay, France
a r t i c l e i n f o
a b s t r a c t
Article history:
A new class of monophosphine ligands has been prepared from natural chirality renewable source,
1,4:3,6-dianhydrohexitol compounds, via a nucleophilic substitution process, or a hydrophosphination
reaction involving microwave activation. These ligands have been evaluated for the rhodium-catalyzed
enantioselective hydrogenation of olefins giving good conversion and enantioselectivity up to 95% and
96% ee, respectively.
Received 7 June 2012
Revised 3 July 2012
Accepted 9 July 2012
Available online 16 July 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Monophosphine ligands
Isosorbide
Isomannide
Hydrogenation
The development of available, inexpensive, modular, and inno-
vative catalysts from biomass products is expected to be one of the
key procedures for expanding the reaction scope and the synthetic
potential of metal-catalyzed enantioselective catalysis.
Isosorbide and isomannide, industrially obtained by dehydra-
tion of D-sorbitol or D-mannitol, represent commercially available
First, our synthesis was inspired by our previous work on the
synthesis of aminoalcohol ligands5 including the selective monob-
enzylation of the hydroxyl group at the endo position C3 of isosor-
bide and the activation of the free hydroxyl group at the exo
position C6 as its sulfonate 3 (Scheme 2). However, the substitution
of 3 with the diphenylphosphine anion failed and produced only
the alcohol 2.
We then chose the isomannide as starting material. Indeed,
benzylation of isomannide gave the monobenzylated compound
5 in 48% yield. Bromination of 5 afforded a mixture of 4a and 4b
in 28% and 66% yields respectively.4d 4a and 4b were easily sepa-
rated by flash chromatography on silica gel. At this point, the exo
configuration of the carbon C6 for compound 4b was confirmed
by X-ray analysis (Scheme 3, see SI, Figure A).
and low cost chiral starting materials for the synthesis of sophisti-
cated molecules including chiral ionic liquids,1 phase-transfer cat-
alysts,2 and ligands (amino alcohols, amines, diphosphines,
diphosphites, bis diaminophosphites, diamidophosphites).3,4
We have recently shown that this starting material provides
easy and cost effective access to optically pure functionalized
and stable amino alcohol, or diamine ligands.5 The structure mod-
ification could be easily and efficiently obtained by classical organ-
ic transformations of diol groups.
Although isosorbide or isomannide were described as starting
materials for the synthesis of phosphorus ligands, essentially
bidentate ligands such as diphosphines, diphosphites, bis-
diaminophosphites, or diamidophosphites,6 no example of mono-
phosphine derived from 1,4:3,6-dianhydrohexitol has been
reported so far. Presently, the application field of monophosphine
in organometallic catalysis has received much attention, particu-
larly for organocatalysis.7 We report herein the synthesis of chiral
monophosphines 1 derived from isosorbide and isomannide and
their use as ligand for enantioselective hydrogenation of olefins
(Scheme 1).
Introduction of phosphine group consists of the nucleophilic
substitution of 4a or 4b. Phosphine-borane complexes 6a and 6b
were obtained from 4a or 4b respectively after protection with
borane dimethylsulfide complex (Scheme 4).
HO
HO
HO
H
H
H
H
H
H
O
O
O
or
O
O
O
PPh2
OH
OH
Exo-1
Endo-1
Isomannide
Isosorbide
⇑
Corresponding authors. Fax: +33 169154680.
E-mail address: giang.vo-thanh@u-psud.fr (G. Vo-Thanh).
Scheme 1. Structure of monophosphines.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.035

H. Ibrahim et al. / Tetrahedron Letters 53 (2012) 4900–4902
4901
HO
BnO
H
H
H
H
PhSO2Cl
O
6
O
3
BnCl, LiH, LiCl
NEt3
99%
DMSO
56%
O
O
OH
OH
2
Isosorbide
BnO
BnO
H
1) ClPPh2, Li
THF
H
O
O
O
O
2) BH3.Me2S
H
H3B
H
PPh2
OSO2Ph
3
Scheme 2. Synthesis of monophosphine from isosorbide.
Figure 1. ORTEP drawing of 6b. Ellipsoids are drawn at the 50% probability level.
HO
BnO
H
H
H
H
O
O
BnCl, LiH, LiCl
BnO
BnO
BnO
H
H
DMSO
48%
H
O
O
O
O
O
1) HPPh2, n-BuLi
OH
OH
+
2) BH3.Me2S
5
Isomannide
O
O
O
Et2O
H
H3B
H
H3B
HO
BnO
H
PPh2
PPh2
H
H
Br
Br2, PPh3, Imidazole,
CH3CN, reflux
O
O
+
6b : 11% yield
7b : 40% yield
4b
O
O
H
H
Br
4a : 28%
Br
BnO
4b : 66%
ratio 7b / 6b = 70/30
H
H
O
Scheme 3. Synthesis of bromo derivatives from isomannide.
O
8
RO
RO
H
H
H
Scheme 5. Synthesis of monophosphines 6b and 7b.
O
O
1) ClPPh2, Li
2) BH3
. Me2S
THF
O
O
H
Br
PPh2
Table 1
Hydrophosphination of 8
H3B
6a: R = H (30%)
4a: R = H
BnO
H
BnO
BnO
O
HPPh2 BH3.Me2S
H
H
H
6b: R = Bn (54%)
4b: R = Bn
O
O
-BuOK
DMSO, 50°C
90%
t
Scheme 4. Synthesis of monophosphines 6a and 6b.
Δ or MW,
O
O
O
solvent
H
H
H3B
OSO2Ph
PPh2
8
3
6b
Surprisingly, X-ray analysis of pure crystals from 6b and 6a con-
firms an exo position of phosphine group due to a total retention of
configuration during the substitution step (Fig. 1 and SI, Figure B).
This was already observed by Dervisi and co-workers when they
carried out the synthesis of isomannide-based diphosphine from
the corresponding dibromide.6a It was demonstrated that the
choice of solvent had an important effect on stereochemistry. The
presence of Et2O favors the endo product, whereas THF gave the exo
as the major product.
b
Conditionsa Solvent T (°C) T (h) Conversion (%) Isolated yield (%)
—
—
Et2O
THF
PhCH3
PhCH3
20
20
60
50
96
145
72
5
0
—
65
<10
>95
—
Oil bath
MW
ndc
47
a
b
c
Reaction was carried out using an oil bath or in a CEM microwave reactor.
Determined by 1H NMR.
Not determined.
By adding LiPPh2 formed by addition of n-BuLi on HPPh2 in
diethylether following by addition of BH3ÁMe2S, we obtained a
mixture of endo-7b/exo-6b (70/30) of desired phosphine boranes
(Scheme 5). Endo-phosphine borane 7b and exo-phosphine borane
6b were isolated in 40% and 11% yields, respectively.
We thought that the obtaining of the compound 6b with the
unexpected ‘exo’ configuration could be explained by a hydropho-
sphination of the alkene 8 which could be obtained in situ from
4b by an elimination process in the presence of LiPPh2 (Scheme
5).8 The stereoselectivity could be easily explained by the attack
of PPh2 anion on the less hindered face of the alkene 8. However,
when performing the reaction of diphenylphosphine and alkene
89 in Et2O at 20 °C for 96 h, no conversion was observed (Table 1).
In THF, only a trace of hydrophosphination product was detected
BnO
HO
HO
H
H
H
H
H
1) HBF4 .OEt2
O
O
O
2) NaHCO3
quant.
O
O
O
H
H3B
PPh2
PPh2
PPh2
Endo-1
Exo-1
6b, 7b
Scheme 6. Obtaining of momophosphines endo-and exo-1.
by 31P NMR analysis after 145 h. On the other hand, using toluene
as a solvent in classical heating conditions, very low conversion
was observed (<10%) after 72 h of reaction. We turned our attention

4902
H. Ibrahim et al. / Tetrahedron Letters 53 (2012) 4900–4902
Table 2
tivity to date for hydrogenation catalysts incorporating a mono-
Hydrogenation of activated olefinsa
phosphine ligand. During our work, we have also reported a new
way to conduct the phosphines using microwave-assisted olefin
hydrophosphination. Development of theses phosphorus com-
pounds as ligands or organocatalysts in asymmetric catalysis is
currently underway in our laboratory.
1 mol% Rh[(COD)2]BF4
CO2R2
NHAc
CO2R2
NHAc
2.2 mol%L*
H2 (1 atm.) / MeOH
rt
*
R1
R1
L⁄
R1
R2
T1/2
Conversionb (%)
Eec (%)
Acknowledgments
exo-1
exo-1
exo-1
exo-1
exo-1
endo-1
Ph
Ph
Ph
H
H
Ph
Me
Me
H
Me
H
8 min
24 h
17 min
4 min
6 min
>95
85
>95
>95
>95
(S)-57
(S)-71d
(S)-30
(S)-72
(S)-70
We wish to thank the French Ministry of Education and Re-
search (MENESR), the CNRS and the University Paris-Sud 11 for
financial supports.
Me
No reaction
a
Reactions were carried out at room temperature under atmospheric pressure of
dihydrogen with 1 mol % of Rh(COD)2BF4 and 2.2 mol % of ligand.
Supplementary data
b
Determined by 1H NMR.
c
Determined by chiral HPLC analysis.
Reaction at À10 °C for 24 h.
d
Supplementary information (SI) available: experimental proce-
dure, characterisation of all new compounds. CCDC 819788 (6b);
819789 (4b) and 819790 (6a) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/datarequest/cif.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.
07.035.
Table 3
Hydrogenation of itaconic acid derivativesa
1 mol% Rh[(COD)2]BF4
CO2R
CO2R
2.2 mol% exo-1
*
H2 (1 atm.) / MeOH
rt
RO2C
RO2C
References and notes
R
T1/2 (min)
Conversionb (%)
Eec (%)
H
Me
47
55
>95
>95
(S)-32
(S)-96
1. (a) Nguyen Van Buu, O.; Aupoix, A.; Doan Thi Hong, N.; Vo-Thanh, G. New J.
Chem. 2009, 33, 2060; (b) Nguyen Van Buu, O.; Aupoix, A.; Vo-Thanh, G.
Tetrahedron 2009, 65, 2260; (c) Kumar, V.; Olsen, C. E.; Schaffer, S. J. C.; Parmar,
V. S.; Malhotra, S. V. Org. Lett. 2007, 9, 3905; (d) Truong, T. K. T.; Nguyen Van
Buu, O.; Aupoix, A.; Pégot, B.; Vo-Thanh, G. Curr. Org. Synth. 2012, 1, 53.
2. Kumar, S.; Ramachandran, U. Tetrahedron 2005, 61, 4141.
a
b
c
Reactions were carried out under 1 atm of hydrogen at room temperature.
Determined by 1H NMR.
Determined by chiral HPLC analysis.
3. For amino-alcool and diamine ligands, see: (a) Guillarme, S.; Nguyen, T. X. M.
Tetrahedron: Asymmetry 2008, 19, 1450; (b) Paolucci, C.; Rosini, G. Tetrahedron:
Asymmetry 2007, 18, 2923; (c) Lui, F. W.; Yan, L.; Zhang, J. Y.; Liu, H. M.
Carbohydr. Res. 2006, 314, 332; (d) Decoster, G.; Vandyck, K.; Van der Eycken,
E.; Van der Eycken, J.; Elseviers, M.; Röper, H. Tetrahedron: Asymmetry 2002, 13,
1673.
4. For phosphorus ligands, see: (a) Diéguez, M.; Pàmies, O.; Claver, C. J. Org. Chem.
2005, 70, 3363; (b) Gavrilov, K. N.; Zheglov, S. V.; Vologzhanin, P. A.;
Maksimova, M. G.; Safronov, A. S.; Lyubimov, S. E.; Davankov, V. A.;
Schäffner, B.; Börner, A. Tetrahedron Lett. 2008, 49, 3120; (c) Reetz, M. T.;
Neugebauer, T. Angew. Chem., Int. Ed. 1999, 38, 179; (d) Zhou, H.; Hou, J.; Cheng,
J.; Lu, S.; Fu, H.; Wang, H. J. Organomet. Chem. 1997, 543, 227; (e) Reetz, M. T.;
Mehler, G. Angew. Chem., Int. Ed. 2000, 39, 3889; (f) Gavrilov, K. N.; Zheglov, S.
W.; Vologzhanin, P. A.; Rastorguev, E. A.; Shiryaev, A. A.; Maksimova, M. G.;
Lyubimov, S. E.; Benetsky, E. B.; Safronov, A. S.; Petroveskii, P. V.; Davankov, V.
A.; Shäffner, B.; Börner, A. Russ. Chem. Bull. Int. Ed. 2008, 57, 2311; (g) Sharma, R.
K.; Samuelson, A. G. Tetrahedron: Asymmetry 2007, 18, 2387.
5. (a) Huynh, K. D.; Ibrahim, H.; Toffano, M.; Vo-Thanh, G. Tetrahedron: Asymmetry
2010, 21, 1542; (b) Huynh, K. D.; Ibrahim, H.; Kolodziej, E.; Toffano, M.; Vo-
Thanh, G. New J. Chem. 2011, 35, 2622.
6. For monodente phosphorus compound derived from 1,4: 3,6-dianhydrohexitol
see: (a) Carcedo, C.; Dervisi, A.; Fallis, I. A.; Ooi, L.; Malik, K. M. A. Chem.
Commun. 2004, 1236; (b) Bakos, J.; Heil, B.; Marko, L. J. Organomet. Chem. 1983,
253, 249; (c) Yuan, J. C.; Lu, S. J. Organometallics 2001, 20, 2697.
to the use of microwave irradiation (MW). This technique was
widely developed in our laboratory and in other research groups.10
Under microwave activation, an excellent conversion was obtained
after 5 h affording the regioselective exo phosphine 6b in 47% yield
after purification by flash chromatography.
Treatment of the phosphines-borane 6b and 7b with an excess
of tetrafluoroboric acid dimethylether complex resulted in a quan-
titative formation of the phosphines exo-1 and endo-1 (Scheme 6).
Complexes formed in situ from Rh[(COD)2]BF4 and exo-1 or
endo-1 ligand were examined as catalysts for the enantioselective
hydrogenation of activated olefins (Table 2).
1H NMR analysis showed that complete conversions were ob-
tained in most of cases in few minutes at room temperature under
the atmospheric pressure of dihydrogen. The products were ob-
tained with satisfactory enantioselectivities when the catalyst
was prepared with exo-1 ligand. Surprisingly, no hydrogenation oc-
curred in the presence of endo-1 ligand. On the other hand, in the
presence of Rh-exo-1 catalyst, itaconic acid was hydrogenated
quantitatively, but with a modest enantiomeric excess (32% ee),
whereas, in the same reaction conditions, its corresponding di-
methyl itaconate conducted a good enantioselectivity up to 96%
ee (Table 3).
7. a Bruneau, C.; Renaud, J. L. In Phosphorus Ligands in Asymmetric Catalysis;
Börner, A., Ed.; Wiley-VCH: Weinheim, 2008; Vol. 1, pp 5–33; (b)Mathey, F.,
Ed.Science of Synthesis Applications of Tricoordinated Phosphorus Compounds
in Heterogeneous Catalysis; Thieme Verlag: Stuttgart, 2009; Vol. 42,. Chapter
10 (c) Marinetti, A.; Voituriez, A. Synlett 2010, 174; (d) Wei, Y.; Shi, M. Acc.
Chem. Res. 2010, 43, 1005; (e) Hayashi, T. Acc. Chem. Res. 2000, 33, 354; (f)
Hayashi, T.; Wook Han, J.; Takeda, A.; Tang, J.; Nohmi, K.; Mukaide, K.; Tsuji, H.;
Uozumi, Y. Adv. Synth. Catal. 2001, 343, 279.
In summary, we have developed a synthesis of new monophos-
phine ligands derived from isosorbide and isomannide, natural
renewable sources. The initial results in asymmetric catalysis such
as hydrogenation of olefins showed good catalytic activity and
enantioselectivity, up to 96% ee for dimethyl itaconic ester.
Although the results are certainly still quite modest with respect
to what can be achieved by using well-developed enantioselective
hydrogenation catalysts, this represents the highest enantioselec-
8. Join, B.; Lohier, J. F.; Delacroix, O.; Gaumont, A. C. Synthesis 2008, 19, 3121.
9. Compound 8 was prepared from 3 by an elimination process in the presence of
t-BuOK as base.
10. For recent reviews on microwave chemistry, see: (a) Loupy, A. Microwaves in
Organic Synthesis; Wiley-VCH: Weinheim, 2006; (b) Kappe, C. O.; Stadler, A.
Microwaves in Organic and Medicinal Chemistry; Wiley-VCH: Weinheim, 2005;
(c) Polshettiwar, V.; Varma, R. S. Acc. of Chem. Res. 2008, 41, 629; (d) Aupoix, A.;
Pégot, B.; Vo-Thanh, G. Ultrasound and Microwaves: Recent Advances in Organic
Chemistry, 2011, 57. Edition: Research Signpost Trans world Research Network.
ISBN: 978-81-7895-532-2.