Synthesis and first application of a new family of monophosphine ferrocene ligands (MOPF)

Article abstract of DOI:10.1039/a908921g

A new family of monophosphine ferrocene ligands (MOPF) has been synthesised in two steps from an optically pure ferrocenyl sulfoxide and the first preliminary studies employing these ligands in asymmetric hydrosilylation of styrene are presented.

Full text of DOI:10.1039/a908921g

Synthesis and first application of a new family of monophosphine ferrocene
ligands (MOPF)
Henriette L. Pedersen and Mogens Johannsen*
Department of Organic Chemistry, Technical University of Denmark, Building 201, DK-2800 Lyngby, Denmark.
E-mail: okmj@pop.dtu.dk
Received (in Liverpool, UK) 9th November 1999, Accepted 11th November 1999
A new family of monophosphine ferrocene ligands (MOPF)
has been synthesised in two steps from an optically pure
ferrocenyl sulfoxide and the first preliminary studies em-
ploying these ligands in asymmetric hydrosilylation of
styrene are presented.
During the last decades only very few efficient chiral monop-
hosphine ligands have been developed, in which the only Lewis
base is the phosphorus atom. The fact that bisphosphine ligands
form more rigid and stable complexes with metals, as compared
to those with monophosphines, has probably stimulated the
more abundant research in the former type. However, recently it
has become increasingly clear that there is a need for efficient
chiral monophosphine ligands for use in those reactions where
the usual C2-symmetric bisphosphines (e.g. BINAP) fail.1
Scheme 1 Reagents and conditions: i, LDA (1.2 equiv.), THF, 278 °C, 20
min, then ZnCl2 (1 equiv.) 278 °C, 1 h, then Pd2dba3 (2 mol%), P(fur)3 (8
mol%), aryl iodide, (1.5 equiv.), (R = H) room temp., 96 h, 67%, (R =
OMe) reflux, 72 h, 54%; ii, (2 equiv.) ButLi, THF, 278 °C, 5 min; then
ClPPh2, (3.5 equiv.) room temp., 3 h, (R = H) 67%, (R = OMe) 76%.
The potential and efficiency of the MOPF ligands is
exemplified in the asymmetric hydrosilylation of styrene.7 This
transformation belongs to the class of reactions where e.g.
BINAP gives only poor results.1a However, using the most
simple phenyl-MOPF ligand 2a the reaction proceeds nicely
with up to 70% ee (Table 1, entries 1 and 2). Introducing a
simple methoxy substituent on the aryl group interferes slightly
with the selectivity of the reaction and it is observed that the
addition of benzene as solvent improves the enantioselectivity
from 60 to 64% (entries 3 and 4). Currently, we have no
information on the catalytically active species in this reaction,
but it is noteworthy that a similar but more pronounced
behaviour has been observed in the hydrosilylation of styrene
using H-MOP (91% ee) and MeO-MOP (14% ee) as ligands.8
Moreover the sense of induction in the reactions using the (S)-
MOPF or the (S)-H-MOP ligands is the same. The rationalisa-
tion of these observations, however, must await further study.
In summary, a short and efficient synthesis of two members
of a novel family of monodentate phosphine ferrocene ligands
(MOPF) has been carried out. The simple procedure developed
paves the way for the preparation of an array of structurally
varied aryl-MOPF ligands. The preliminary catalytic reactions
employing these ligands have given encouraging results and we
One of the few efficient types of monophosphine ligands
discovered to date is Hayashi’s MOP ligands 1.1a,2 Here we
disclose a new family of arylMOnoPhosphinoFerrocene ligands
2 (herafter abbreviated MOPF), which show some resemblance
to the MOP ligands, but are simpler to modify in a rational
manner.3
We also present the first catalytic reactions employing these
new ligands. In terms of enantioselectivity, the results are very
encouraging and we believe that they can be further improved
by simple variation of the aryl unit.
During the initial phase of this project we searched for a
simple procedure to obtain a suitable building block for this new
family of ligands. Recently, great progress has been achieved
within the field of Directed ortho-Metallation (DoM) of
ferrocenes.4 However, the enantioselective ortho-lithiation of
e.g. diphenylphosphinoferrocene, which in principle would
allow us to synthesise these ligands in a single step, has met with
only limited success.5 On the other hand, Kagan et al.4a,6 and
Robinson et al.4b have recently described highly selective
ortho-lithiation procedures of optically pure ferrocenyl sulf-
oxides. As the sulfoxide can be removed from the ferrocene by
treatment with ButLi we chose this compound as a starting
material for the synthesis of the MOPF ligands. The synthesis of
the first two members of the MOPF family is shown in Scheme
1. After diastereoselective ortho-lithiation of the sulfoxide (S)-
34a and lithium–zinc exchange, the aryl scaffold is introduced
by a Negishi coupling giving 4. The selective removal of the
sulfoxide is accomplished with ButLi and the lithiated ferrocene
is then captured with ClPPh2 giving the ligands (S)-2a,b.
Table 1 Enantioselective hydrosilylation of styrene using MOPF ligands
2a,b.9
Yield of
5 (%)a
Ee of 6
(%)bc
Entry
Ligand
t/h
T/°C
1
2
3
4
a
2a
2a
2b
2b
24
36
36
72
room temp.
room temp.
room temp.
room temp.
66
73
49
41d
70 (S)
70 (S)
60 (S)
64 (S)e
b
Isolated yield after destillation or flash chromatography. Ee deter-
c
mined by HPLC on a DAICEL OD-H column. Absolute configuration
determined by optical rotation [see ref. 2(b)]. d Yield of 6 based on styrene.
e Benzene added as solvent.
Chem. Commun., 1999, 2517–2518
This journal is © The Royal Society of Chemistry 1999
2517

references prior to 1996 see: A. Togni, Angew. Chem., 1996, 108,
1581.
5 D. Price and N. S. Simpkins, Tetrahedron Lett., 1995, 36, 6135.
6 F. Rebière, O. Riant, L. Richard and H. B. Kagan, Angew. Chem., 1993,
105, 644.
7 For other asymmetric hydrosilylation reactions of styrene see e.g.: G.
Bringmann, A. Wuzik, M. Breuning, P. Henschel, K. Peters and E.-M.
Peters, Tetrahedron: Asymmetry, 1999, 10, 3025; G. Pioda and A.
Togni, Tetrahedron: Asymmetry, 1999, 9, 3903; T. Okada, T. Morimoto
and K. Achiwa, Chem. Lett., 1990, 999.
are pursuing the synthesis of a range of new aryl-MOPF as well
as alkyl-MOPF family members in order to find even better
ligands.10
Leo Pharmaceutical Products, the Technical University of
Denmark and the Danish Ministry of Education are gratefully
acknowledged for funding.
Notes and references
8 This selectivity has been shown to be substrate dependent. MeO-MOP
generally gave better results than H-MOP using non-styrene-type
substrates such as e.g. oct-1-ene (up to 96% ee) [ref. 2(b)]. We are
currently investigating the MOPF ligands to see whether they display
similar behaviour.
1 For some examples where monophosphine ligands or ligands with a
phosphine and a hemilabile coordinating group are superior to the usual
bisphosphines, see e.g.: (a) Asymmetric hydrosilylation: Y. Uozumi and
T. Hayashi, J. Am. Chem. Soc., 1991, 113, 9887; (b) Asymmetric
hydrovinylation: T. V. RajanBabu, N. Nomura, J. Jin, B. Radetich, H.
Park and M. Nandi, Chem. Eur. J., 1999, 5, 1963; (c) Asymmetric
Grignard cross-coupling: T. Hayashi, K. Hayashizaki, T. Kiyoi and Y.
Ito, J. Am. Chem. Soc., 1988, 110, 8153.
2 For the synthesis and application of MOP and other monophosphine
ligands see e.g.: (a) Y. Uozumi, A. Tanahashi, S.-Y. Lee and T. Hayashi,
J. Org. Chem., 1993, 58, 1945; (b) K. Kitayama, Y. Uozumi and T.
Hayashi, J. Chem. Soc., Chem. Commun., 1995, 1533; (c) H. Tye, D.
Smyth, C. Eldred and M. Wills, Chem. Commun., 1997, 1053; (d) C. D.
Graf, C. Malan, K. Harms and P. Knochel, J. Org. Chem., 1999, 64,
5581; (e) G. Zhu, Z. Chen, Q. Jiang, D. Xiao, P. Cao and X. Zhang,
J. Am. Chem. Soc., 1997, 119, 3836; (f) B. L. Feringa, M. Pineschi, L.
A. Arnold, R. Imbos and A. H. M. de Vries, Angew. Chem., Int. Ed.
Engl., 1997, 36, 2620; (g) B. Bartels and G. Helmchen, Chem.
Commun., 1999, 741.
3 The MOPF ligands are structurally different from known ferrocene
monophosphines which have a methylene spacer group next to the
phosphine. See e.g. T. Hayashi, in Ferrocenes, ed. A. Togni and T.
Hayashi, VCH, Weinheim, 1995, p. 118.
4 (a) O. Riant, G. Argourch, D. Guillaneux, O. Samuel and H. B. Kagan,
J. Org. Chem., 1998, 63, 3511; (b) D. H. Hua, N. M. Lagneau, Y. Chen,
P. M. Robben, G. Clapham and P. D. Robinson, J. Org. Chem., 1996, 61,
4508; (c) M. Tsukazaki, M. Tinkl, A. Roglans, B. J. Chapell, N. J.
Taylor and V. Snieckus, J. Am. Chem. Soc., 1996, 118, 685; (d) For
9 A representative hydrosilylation–oxidation procedure: To a flame dried
Schlenk tube was added [ClPd(C3H5)]2 (6.2 mg, 0.017 mmol) and 2b
(30 mg, 0.067 mmol) under N2. The solids were dried on the vacuum
line for 1 h before styrene (0.378 ml, 3.3 mmol) and 2 ml of benzene
were added via syringe. After another 30 min the silane (0.404 ml, 4
mmol) was added via syringe and the solution was left with stirring for
72 h. An aliquot of the reaction was used for NMR and it showed that
the reaction was completed. The crude reaction mixture was slowly
added to a suspension of KF (3.9 g, 67 mmol) in 30 ml of MeOH and the
resulting solution was stirred for 30 min. The solvent was evaporated in
vacuo and the resulting solid was suspended in 40 ml of DMF. Finally
4 ml H2O2 (35%) was added at room temperature and the reaction was
heated to 60 °C for 1 h before quenching with 30 ml saturated Na2S2O3
(aq). After aqueous workup and extraction the product was purified by
flash column chromatography (15% EtOAc in pentane) giving 6 as a
colorless oil in 41% yield (167 mg) and 64% ee detected by HLPC using
a Chiralcel OD-H column (10% PriOH–90% hexane, 0.5 ml min21).
[a]rDt –36 (c 1.065, CHCl3). Spectroscopic data were in accordance with
those from a commercial sample.
10 During the course of our investigation we became aware of a paper from
another group synthesising related benzene chromium tricarbonyl
complexes. This prompted us to report our findings at this early stage.
See: S. C. Nelson and M. A. Hilfiker, Org. Lett., 1999, 1, 1379.
Communication 9/08921G
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Chem. Commun., 1999, 2517–2518