1-Phosphino-2-sulfenylferrocenes: Efficient ligands in enantioselective palladium-catalyzed allylic substitutions and ring opening of 7-oxabenzonorbornadienes

Article abstract of DOI:10.1039/b207344g

The readily available 1-phosphino-2-sulfenylferrocenes 1 provide very high enantioselectivities in Pd-catalyzed allylic substitution reactions and alkylative ring opening of 7-oxabenzonorbornadiene with dialkylzinc reagents.

Full text of DOI:10.1039/b207344g

1
-Phosphino-2-sulfenylferrocenes: efficient ligands in enantioselective
palladium-catalyzed allylic substitutions and ring opening of
-oxabenzonorbornadienes†
7
Julián Priego, Olga García Mancheño, Silvia Cabrera, Ramón Gómez Arrayás, Tomás Llamas and
Juan C. Carretero*
Departamento de Química Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid,
Cantoblanco, 28049 Madrid, Spain. E-mail: juancarlos.carretero@uam.es; Fax: +34 913973966; Tel: +34
913973925
Received (in Cambridge, UK) 26th July 2002, Accepted 20th September 2002
First published as an Advance Article on the web 7th October 2002
The readily available 1-phosphino-2-sulfenylferrocenes 1
provide very high enantioselectivities in Pd-catalyzed allylic
substitution reactions and alkylative ring opening of 7-ox-
abenzonorbornadiene with dialkylzinc reagents.
The use of mixed bidentate ligands equipped with strong and
weak donor heteroatom pairs has proved to be one of the most
useful concepts in asymmetric catalysis. Although much less
studied than the mixed P,N-coordination mode, some recent
reports indicate that P,S-bidentate ligands based on chiral
thioethers can also lead to high enantioselectivities in C–C bond
forming metal-catalyzed reactions.1 However, P,S-bidentate
ligands possessing planar chirality as the only source of
chirality have not been previously studied. We describe herein
that the readily available enantiopure P,S-bidentate ferrocenes 1
act as very efficient ligands in Pd-catalyzed allylic substitutions
and alkylative ring opening of 7-oxabenzonorbornadiene.
The preparation of the starting sulfinylferrocene 2 had been
previously reported either by sulfinylation of ferrocenyllithium
Scheme 1 Reagents and conditions: i, t-BuLi, THF, 278 °C; R
2
PCl; ii,
HSiCl , Et N, toluene, 110 °C; iii, LDA, THF, 278 °C; Ph PCl (ref. 7).
3
3
2
with enantiopure tert-butylsulfinates, or by asymmetric oxida-
2
tion of tert-butylsulfenylferrocene. Alternatively, we have
recently reported3 that (R)-2 can be readily prepared in
multigram scale by sulfinylation of ferrocenyllithium with (R)-
(
entry 6), which afforded 4 in low ee. This suggests that a high
sterically demanding substitution at the sulfur atom in ligands 1
is crucial for reaching a high stereochemical control.
4
S-tert-butyl tert-butanethiosulfinate. It was well established
2
from the work of Kagan and coworkers
and Hua and
Ligands 1a–f were next tested in Pd-catalyzed allylic
substitution with nitrogen nucleophiles, such as benzylamine
and potassium phthalimide (KPhth) (Table 2). In the presence of
5
coworkers that the ortho-lithiation of (R)-2 occurs with nearly
complete diastereocontrol at C-2. Accordingly, the treatment of
(R)-2 with tert-butyllithium and a chlorophosphine led to the
1
2
a the reaction with BnNH afforded (S)-5 in 97% ee and the
corresponding (RFc, R ) sulfinylferrocenyl phosphine 3 in good
S
reaction with phthalimide gave (S)-6 in 91% ee. Interestingly,
the electronically poor phosphines 1b and 1c provided again the
best results (ee up to 99%).
6
yield (66–91%) and complete diastereoselectivity (de > 96%).
The further reduction of the sulfoxide to the sulfide moiety was
cleanly achieved with HSiCl
affording the enantiopure planar chiral ferrocenes 1a–e (ee
99%; HPLC, Chiralcel OD) (Scheme 1). The enantiopure p-
3 3
–Et N in refluxing toluene,
The behavior of ferrocenes 1 as P,S-bidentate ligands was
10
demonstrated by X-ray crystallographic study of the complex
1a)PdCl (Fig. 1), which was readily prepared by treatment of
a with Pd(CH CN) Cl in CH Cl (72% yield). Important
>
(
2
tolylsulfenyl ferrocene (S)-1f was readily prepared from (S)-p-
tolylsufinylferrocene2 following the same synthetic ap-
proach.
1
3
2
2
2
2
,7
structural information deduced from this study is the anti
These sterically and electronically varied ferrocenes 1a–f
were evaluated as chiral ligands in the standard Pd-catalyzed
Table 1 Pd-catalyzed reaction of 1,3-diphenyl-2-propenyl acetate with
dimethyl malonate in the presence of ligands 1
8
allylic substitution of dimethyl malonate with 1,3-diphenyl-
2
-propenyl acetate (Table 1). Interestingly, we found that this
transformation was deeply accelerated by addition of a catalytic
9
amount of Bu
reaction at 220 °C, therefore improving the enantioselectivity
values in brackets). Remarkably, the parent ligand 1a and the
4
NCl (10 mol%), which allows us to carry out the
(
phosphines 1b and 1c, having electron-withdrawing sub-
stituents, provided (R)-4 with very high enantioselectivity (ee
up to 96–97% at 220 °C). In contrast, a decrease in the
asymmetric induction was observed with the more electron-rich
phosphines 1d and 1e (entries 4 and 5). A much more dramatic
effect was found in the case of the p-tolylsulfenylferrocene 1f
Entry
Ligand
Yield (%)
a
Ee (%)
b
c
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
92
94
90
60
96
92
b
93 (96)
92 (97)
92 (96)
90
c
c
84
d
40
†
Electronic supplementary information (ESI) available: experimental
a
In pure product after chromatography. Determined by HPLC (Chiralcel
OD). Enantiomeric excess at 220 °C. d Enantiomeric excess of (S)-4.
details and determination of enantiomeric excesses. See http://www.rsc.org/
suppdata/cc/b2/b207344g/
c
2
512
CHEM. COMMUN., 2002, 2512–2513
This journal is © The Royal Society of Chemistry 2002

Table 2 Pd-catalyzed reaction of 1,3-diphenyl-2-propenyl acetate with
benzylamine and phthalimide in the presence of ligands 1
Table 3 Pd-catalyzed reaction of oxabenzonorbornadiene with dialkylzinc
reagents in the presence of ligands 1
Yield (%) Ee (%)b
a
Entry
Ligand
Nu
Product
Yield (%)a
Ee (%)b
Entry
Ligand
R
Product
1
2
3
4
5
6
7
8
a
1a
1a
1b
1b
1c
1d
1e
1f
BnNH
KPhth
BnNH
KPhth
BnNH
BnNH
BnNH
BnNH
2
5
6
5
6
5
5
5
5
b
80
74
89
90
91
60
50
88
97 (97)c
91
98 (99)
1
2
3
4
5
6
7
8
9
a
1a
1a
1b
1b
1c
1c
1e
1e
1f
Et
Me
Et
Me
Et
Me
Et
7a
7b
7a
7b
7a
7b
7a
7b
7a
b
70
72
20
63
16
65
68
73
90
88
81
82
70
67
93
94
6
c
2
c
c
92.5 (96)
2
2
2
2
98
94
40
d
d
e
f
41
Me
Et
e
In pure product after chromatography. Determined by HPLC (Chiralcel
22
c
d
OD). Enantiomeric excess at 220 °C. Conversion yield after 15 h.
In pure product after chromatography. Determined by HPLC (Chiralcel
e
f
Conversion yield after 96 h. Enantiomeric excess of (R)-5.
OD column). c Compound 8 was also obtained in 37% yield. d Compound
8
e
was also obtained in 40% yield. Conversion yield after 3 days.
orientation of the tert-butyl group with regard to the iron atom
and that the Pd–Cl bond trans to the phosphorus is longer than
trans to sulfur (2.35 Å vs. 2.30 Å), reflecting the stronger trans
effect of the phosphine moiety. Taking into account these data,
the high asymmetric efficiency of ligands 1 could be explained
by the preferential attack of the nucleophile trans to phospho-
Financial support of this work by the M.C.Y.T. is gratefully
acknowledged (project BQU2000-0266). R. G. A. thanks the
M.C.Y.T. for a ‘Contrato Ramón y Cajal’. J. P. and O. G. M.
thank the M.E.C. for a predoctoral fellowship. We acknowledge
2
Johnson Matthey PLC for a generous loan of PdCl .
1
rus on the presumed key p-allylpalladium complex inter-
mediate I.
Notes and references
To investigate the application of ligands 1 in other palladium-
catalyzed reactions, we studied the alkylative ring opening of
1
For recent examples, see: A. Albinati, P. S. Pregosin and K. Wick,
Organometallics, 1996, 15, 2419; J. Spencer, V. Gramlich, R. Häusel
and A. Togni, Tetrahedron: Asymmetry, 1996, 7, 41; D. A. Evans, K. R.
Campos, J. S. Tedrow, F. E. Michael and M. R. Gagné, J. Am. Chem.
Soc., 2000, 122, 7905; Y.-Y. Yan and T. V. RajanBabu, Org. Lett.,
2000, 2, 199; D. Enders, R. Peters, R. Lochtman, G. Raabe, J. Runsink
and J. W. Bats, Eur. J. Org. Chem., 2000, 3399; H. Nakano, Y.
Okuyama, M. Yanagida and H. Hongo, J. Org. Chem., 2001, 66, 620; H.
Nakano, Y. Suzuki, C. Kabuto, R. Fujita and H. Hongo, J. Org. Chem.,
7
-oxabenzonorbornadiene with dialkylzinc reagents, recently
11
reported by Lautens et al., in which the efficiency of P,S-
bidentate ligands had not been previously explored. The results
obtained using Pd(CH CN) Cl as catalyst are shown in Table
3 2 2
3
.
The reaction of 7-oxabenzonorbornadiene with Et
Zn in the presence of 1a provided the known alcohols11 7a
Me
2
Zn and
2
2
002, 67, 5011.
and 7b in 90% ee and 88% ee, respectively. In contrast, the
electron-deficient phosphines 1b and 1c, which gave optimal
results in the allylic substitutions, exhibited only modest
performance in the Pd-catalyzed alkylative ring opening
process, affording the racemic alcohol 812 as the major product
in several cases (Table 3, entries 3 and 5). Interestingly, in this
reaction the best results were obtained with the electron-rich
dialkylphosphine 1e (93–94% ee, entries 7 and 8). These
enantioselectivities are among the best reported for this
transformation.11
2
F. Rebière, O. Riant, L. Ricard and H. B. Kagan, Angew. Chem., Int. Ed.
Eng., 1993, 32, 568; P. Diter, O. Samuel, S. Taudien and H. B. Kagan,
Tetrahedron: Asymmetry, 1994, 5, 549.
3 J. Priego, O. García Mancheño, S. Cabrera and J. C. Carretero, J. Org.
Chem., 2002, 67, 1346.
4 D. A. Cogan, G. Liu, K. Kim, B. J. Backes and J. A. Ellman, J. Am.
Chem. Soc., 1998, 120, 8011.
5
N. M. Lagneau, Y. Chen, P. M. Robben, H.-S. Sin, K. Takasu, J.-S.
Chen, P. D. Robinson and D. H. Hua, Tetrahedron, 1998, 54, 7301.
In solution, the phosphines 3 slowly evolve to the corresponding
sulfenylferrocenyl phosphine oxides by an intramolecular oxygen
transfer process. For a similar behaviour, see: K. Hiroi, Y. Suzuki, I.
Abe and R. Kawagishi, Tetrahedron, 2000, 56, 4701.
6
In summary, the readily available bidentate P,S-ligands 1,
having solely planar chirality, provide high enantioselectivities
in Pd-catalyzed allylic substitutions and in the ring opening of
7
O. Riant, G. Argouarch, D. Guillaneux, O. Samuel and H. B. Kagan, J.
Org. Chem., 1998, 63, 3511.
7
-oxabenzonorbornadiene with dialkylzinc reagents. The mod-
ular approach for the preparation of this ligand system allows its
electronic and steric properties to be easily fine-tuned.
8 For a review, see: B. M. Trost and D. L. van Vranken, Chem. Rev., 1996,
96, 395.
9
For a review on halide effects in transition metal catalysis, see: K.
Fagnou and M. Lautens, Angew. Chem., Int. Ed., 2002, 41, 26.
1
0 Crystal data for C26
0.25 mm, M
.7541(5), b = 15.9433(8), c = 16.9386(8) Å, b = 94.8180(10)°, V =
H
27Cl
2
FePPdS [(1a)PdCl
2
]: crystal size 0.08 3 0.25
3
9
2
w
= 635.66, monoclinic, space group P2
1
/n, a =
3
23
21
c
624.9(2) Å , Z = 4, D = 1.609 g cm , m = 1.595 mm , T = 296(2)
K, Mo-Ka radiation (l = 0.71073 Å), 17617 reflections measured,
447 independent (Rint
0.0810). Refinement on F2 for 7447
reflections and 293 parameters gave GOF = 1.067, R = 0.0515, R
.1076 for I > 2s(I). CCDC reference number 185296. See http:/
www.rsc.org/suppdata/cc/b2/b207344g/ for crystallographic data in
7
=
w
=
0
/
CIF or other electronic format.
1
1 M. Lautens, J.-L. Renaud and S. Hiebert, J. Am. Chem. Soc., 2000, 122,
1
804; M. Lautens, S. Hiebert and J.-L. Renaud, J. Am. Chem. Soc., 2001,
123, 6834.
12 M. Lautens and T. Rovis, Tetrahedron, 1998, 54, 1107.
Fig. 1 Crystal structure of (1a)PdCl
complex intermediate I.
2
and proposed key p-allylpalladium
CHEM. COMMUN., 2002, 2512–2513
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