Cationic planar chiral palladium P,S complexes as highly efficient catalysts in the enantioselective ring opening of oxa- and azabicyclic alkenes

Article abstract of DOI:10.1002/anie.200460087

Open plan: Cationic methylpalladium(II) complexes of planar chiral Fesulphos ligands (Fesulphos = 1-phosphanyl-2-sulfenylferrocene) show excellent performance in the alkylative ring opening of oxa- and azabicyclic alkenes with dialkyl zinc reagents (see s

Full text of DOI:10.1002/anie.200460087

Communications
feature that makes them very attractive in asymmetric
catalysis: the sulfur atom becomes stereogenic upon coordi-
nation to the metal, thus imposing a unique asymmetric
environment next to the reactive metal center. In this context,
we recently reported that the planar chiral Fesulphos ligands
1 (1-phosphanyl-2-sulfenylferrocenes) behave as very effi-
cient P,S ligands in Pd-catalyzed allylic substitutions and in
Cu-catalyzed additions to imines.[4]
Among recently described new Pd-catalyzed enantiose-
lective reactions, the ring opening of meso oxabicyclic alkenes
with dialkyl zinc reagents in the presence of chiral P,P and
P,N ligands reported by Lautens et al. constitutes a syntheti-
À
cally outstanding C C bond forming desymmetrization
reaction.[5] According to mechanistic evidence[5b] this alkyla-
tive ring-opening reaction proceeds by coordination and
subsequent enantioselective carbopalladation of the alkene,
with a cationic alkyl palladium intermediate [L2PdR]+ formed
in situ under the reaction conditions employed.[6] Inspired by
this work, we envisaged that the cationic methylpalladium
complexes of Fesulphos ligands [(1)PdMe]+ could act as very
active catalysts in this type of reaction. Herein, we report that
this robust and readily available catalyst system combines low
catalyst loading, high enantioselectivity, easy fine-tuning, mild
reaction conditions, and broad structural scope.
Treatment of ligands 1 with [PdCl2(CH3CN)2][7] afforded
in very high yield the corresponding complexes [(1)PdCl2] as
single epimers at the sulfur atom.[4b] Interestingly, the trans-
metalation reaction of these complexes with Me2Zn was
Ring-Opening Catalysts
Cationic Planar Chiral Palladium P,S Complexes
completely stereoselective, affording
[(1)Pd(Cl)(Me)] in 70–95% yield (Scheme 1). The cis
a single complex
as Highly Efficient Catalysts in the
Enantioselective Ring Opening of Oxa- and
Azabicyclic Alkenes**
arrangement of the methyl group and the phosphane moiety
1
was established by analysis of their H, 13C, and 31P NMR
2
spectra; the low coupling constants JP,C(Me) (< 1.0 Hz) and
3JP,H(Me) (2.4 Hz) were of great diagnostic value.[8] This stereo-
chemical assignment was unequivocally confirmed by X-ray
crystal diffraction analysis[9] of [(1a)Pd(Cl)(Me)] (Figure 1).
Additional relevant structural information includes the
preservation of the anti arrangement of the tert-butyl group
with respect to the iron atom (RP,RS configuration), and the
Silvia Cabrera, Ramón Gómez Arrayµs, and
Juan C. Carretero*
A huge effort has been devoted to the development of highly
efficient asymmetric transition-metal-catalyzed reactions
using chiral ligands based on P,P, P,N or N,N coordination
modes,[1] some of which have reached the status of privileged
ligands.[2] In sharp contrast, thioether-based chiral ligands[3]
have received much less attention, despite a key structural
À
elongation of the Pd S bond (2.444 Š) compared to that of
the starting dichloro complex (2.314 Š)[4b] as result of the
strong trans effect of the highly s-donating methyl group. The
removal of the chloride ion in [(1a)Pd(Cl)(Me)] by treatment
with AgPF6 (CH2Cl2, room temperature) or NaB(ArF)4
[ArF = 3,5-bis(trifluoromethyl)phenyl][10] in the presence of
benzonitrile afforded a single cationic benzonitrile-coordi-
nated palladium species [(1a)Pd(Me)(PhCN)]+ XÀ. The crys-
tal structure of this complex[11] (Figure 1) is very similar to
that of its precursor [1a·Pd(Cl)(Me)] although, as expected,
[*] S. Cabrera, Dr. R. Gómez Arrayµs, Prof. Dr. J. C. Carretero
Departamento de Química Orgµnica
Facultad de Ciencias, Universidad Autónoma de Madrid
Cantoblanco 28049 Madrid (Spain)
Fax: (+34)914-973-966
À
E-mail: juancarlos.carretero@uam.es
the Pd Me bond is even shorter (2.011 versus 2.048 Š) and
À
[**] This work was supported by the MCyT (project BQU2000-0226 and
BQU2003-0508). S.C. thanks the UAM for a predoctoral fellowship.
R.G.A. thanks the MCyT for a Ramón y Cajal contract. We
the Pd S bond is longer (2.461 versus 2.444 Š) as a result of
the enhanced s donation of the methyl group to the cationic
Pd atom.
Table 1 summarizes the most significant results obtained
with this set of potential P,S catalysts in the model reaction of
7-oxabenzonorbornadiene with Me2Zn.
As the starting point we used similar experimental
conditions to those previously described: 5 mol% of catalyst
in toluene or 1,2-dichloroethane (DCE) at room temperature
acknowledge the skilled assistance of Prof. Jaime Rodríguez
Gonzµlez in solving the X-ray crystal structure of the cationic
palladium complex. Prof. JosØ L. García-Ruano is gratefully
acknowledged for unrestricted access to the HPLC equipment of his
group. We thank Johnson Matthey PLC for a generous loan of PdCl2.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200460087
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Angewandte
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produced by adding NaB(ArF)4
(entry 4). A complete conver-
sion was observed within
10 minutes with this noncoordi-
nating counterion. This out-
standing reactivity allowed a
dramatic decrease of the cata-
lyst loading: 0.5 mol% of cata-
lyst drove the reaction to com-
pletion in 30 minutes (entry 5).
As expected, a similar result
was obtained using 0.5 mol% of
the isolated air-stable cationic
complex (entry 6) instead of
catalyst generated in situ.
Scheme 1. Synthesis of Fesulphos palladium complexes. a) Me2Zn (1.5 equiv), CH2Cl2, RT; b) AgPF6 or
NaBArF , PhCN, CH2Cl2, RT. Cy=cyclohexyl.
4
To fine-tune the reactivity and enantioselectivity of the
process, we next studied the effect of the substitution at the
phosphorus atom (complexes of ligands 1b–e). With the
exception of the complex containing the bulky naphthylphos-
phane ligand 1d (entry 9), the reactions were complete in 10–
30 minutes, with the electronically rich phosphane 1e provid-
ing the best enantioselectivity (entry 10). The combination
[(1e)Pd(Cl)(Me)]+NaB(ArF)4 proved to be so effective that
the reaction could be performed with severely decreased
catalyst loading and temperature, which resulted in an
enhancement of the enantioselectivity. Thus, 0.2mol% of
catalyst was sufficient to reach quantitative conversion within
5 h at À258C, which afforded alcohol 2a in 88% yield with
97% ee (entry 11).
Figure 1. X-Ray crystal structures of [(1a)Pd(Cl)(Me)] and
[(1a)Pd(Me)(PhCN)]B(ArF)4 (the B(ArF)4 anion has been omitted for
À
clarity).
With these optimized P,S catalysts in hand, we turned our
attention toward the substrate generality of the process. The
use of 0.5 mol% [(1e)Pd(Cl)(Me)][13] in combination with
NaB(ArF)4 (0.5 mol%) as a halogen scavenger catalyzed the
enantioselective opening of a variety of substituted meso
oxabenzonorbornadienes with both Me2Zn and Et2Zn in
DCE[14] at room temperature. As shown in Scheme 2,
complete conversions within 10–30 minutes, good chemical
yields (61–98%), and excellent enantioselectivities (94–
> 99% ee, HPLC) were obtained for all products 2–5.
(RT).[5] Catalyst [(1a)PdCl2] led to 80% conversion in
24 hours (entry 1) to give the cis alcohol (R,R)-2a[12] with a
remarkable 81% ee. A similar result was achieved using the
methyl complex [(1a)Pd(Cl)(Me)] (entry 2), which supports
the proposal that both complexes evolve to the same active
catalyst under the reaction conditions used. A significant
increase in the reaction rate occurred when a catalytic amount
of AgPF6 was added to dissociate the chloride ligand
(entry 3). However, the greatest acceleration effect was
Table 1: Ring opening of 7-oxabenzonorbornadiene with Me2Zn catalyzed by palladium complexes of ligands 1.
Entry
Catalyst (x mol%)
Additive (x mol%)
t (min)
Yield [%][a]
ee [%][b]
1
2
3
4
5
6
7
8
9
[(1a)PdCl2] (5)
–
–
1440
2880
420
10
30
30
15
30
360
10
300
80[c]
75[c]
83
86
78
82
71
74
80
81
85
83
78
78
72
69
64
46
83
97
[(1a)Pd(Cl)(Me)] (5)
[(1a)Pd(Cl)(Me)] (5)
[(1a)Pd(Cl)(Me)] (5)
[(1a)Pd(Cl)(Me)] (0.5)
AgPF6 (5)
NaBArF (5)
4
NaBArF (0.5)
4
[(1a)Pd(Me)(PhCN)]+(BArF )À (0.5)
–
4
[(1b)Pd(Cl)(Me)] (5)
[(1c)Pd(Cl)(Me)] (5)
[(1d)Pd(Cl)(Me)] (5)
[(1e)Pd(Cl)(Me)] (5)
[(1e)Pd(Cl)(Me)] (0.2)
NaBArF (5)
4
NaBArF (5)
4
NaBArF (5)
4
10
NaBArF (5)
77
88
4
11[d]
NaBArF (0.2)
4
[a] In pure product. [b] HPLC (Chiralpak AD column). [c] Conversion yield. [d] In 1,2-dichloroethane at À258C.
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3945

Communications
effect of the phosphorus moiety and the great
steric control exerted by the close, bulky stereo-
genic sulfur substituent would be responsible for
the high asymmetric induction in the key
carbopalladation step (Scheme 4).
In summary, the cationic methylpalladium
species derived from the readily available planar
chiral P,S ligands 1 display an excellent profile as
catalysts for the enantioselective alkylative ring
Scheme 2. Alcohols 2–5 resulting from the reaction of substituted oxabenzonorbornadienes with
Me2Zn and Et2Zn catalyzed with [(1e)PdMe]+. [a] The reaction was carried out at À258C.
Finally, to test the efficiency of these highly active
catalysts toward much less reactive bicyclic substrates, we
studied the opening reaction of nonaromatic [2.2.1]oxabicy-
clic alkenes and azabenzonorbornadienes, which usually
require harsher reaction conditions.[5c] Notably, [(1a)PdMe]+
and [(1e)PdMe]+ (1 mol%) induced the ring opening of the
[2.2.1]oxabicyclic alkene with Me2Zn within three hours at
room temperature, which led to cyclohexenol 6a[12] in
96–97% ee (Scheme 3).
Scheme 4. Mechanistic proposal.
opening of oxa- and azabicyclic alkenes with dialkyl zinc
reagents. The structure of these catalysts suggests that the
high asymmetric induction relies on the strong trans effect of
the phosphane moiety that acts in combination with the
sterically demanding environment imposed by the stereo-
genic sulfur atom directly bonded to the palladium atom.
Received: March 22, 2004 [Z460087]
Scheme 3. Ring opening of less reactive meso substrates. TBDPS=tert-butyldi-
phenylsilyl, Ts=toluene-4-sulfonyl. [a] The reaction was carried out with 5 mol%
of catalyst.
Keywords: alkenes · asymmetric catalysis · ferrocenyl ligands ·
palladium · S ligands
.
[1] a) Comprehensive Asymmetric Catalysis (Eds.: E. N. Jacobsen,
A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999; b) Catalytic
Asymmetric Synthesis (Ed.: I. Ojima), Wiley, New York, 2000.
[2] T. P. Yoon, E. N. Jacobsen, Science 2003, 299, 1691 – 1693.
[3] For leading recent references on P,S ligands in enantioselective
catalysis, see: sulfenyl phosphinites: a) D. A. Evans, F. E.
Michael, J. S. Tedrow, K. R. Campos, J. Am. Chem. Soc. 2003,
125, 3534 – 3543; b) T. Kanayama, K. Yoshida, H. Miyabe, Y.
Takemoto, Angew. Chem. 2003, 115, 2100 – 2102; Angew. Chem.
Int. Ed. 2003, 42, 2054 – 2056; c) D. A. Evans, K. R. Campos, J. S.
Tedrow, F. E. Michael, M. R. Gagne, J. Am. Chem. Soc. 2000,
122, 7905 – 7920; sulfenyl phosphines: d) T. Tu, Y.-G. Zhou, X.-L.
Hou, L.-X. Dai, X.-C. Dong, Y.-H. Yu, J. Sun, Organometallics
2003, 22, 1255 – 1265; e) H. Nakano, Y. Suzuki, C. Kabuto, R.
Jujita, H. Hongo, J. Org. Chem. 2002, 67, 5011 – 5014; f) D.
Enders, R. Peters, R. Lochtman, G. Raabe, J. Runsik, J. W. Bats,
Eur. J. Org. Chem. 2000, 3399 – 3426; g) X. Verdaguer, A.
Moyano, M. A. Pericàs, A. Riera, M. A. Maestro, J. Mahía, J.
Am. Chem. Soc. 2000, 122, 10242 – 10243.
The most reactive catalyst for the opening of the
azabenzonorbornadiene derivative was the complex
[(1a)Pd(Me)(PhCN)]+(PF6)À. In the reaction with Me2Zn
the ring-opened product (R,R)-7a was obtained within
30 minutes (73% yield) with virtually complete enantiocon-
trol (> 99% ee) by using 5 mol% of catalyst. The use of
1 mol% of catalyst resulted in a much slower reaction (60%
conversion after 48 h). The reaction with Et2Zn was faster, but
surprisingly much less enantioselective, and gave 7b in
33% ee.
According to the X-ray structures shown in Figure 1, the
high enantioselectivity displayed by these P,S-palladium
species could be explained by assuming a combination of
electronic and steric factors: a) coordination of the bicyclic
alkene trans to the phosphorus atom on the palladium center;
and b) coordination of the alkene from its less hindered exo
face, with orientation of the oxygen (or nitrogen) bridge to
the opposite side of the very bulky tert-butyl group. Thus, the
synergetic effect derived from the strong electronic trans
[4] a) O. García Mancheæo, R. Gómez Arrayµs, J. C. Carretero, J.
Am. Chem. Soc. 2004, 126, 456 – 457; b) O. García Mancheæo, J.
Priego, S. Cabrera, R. Gómez Arrayµs, T. Llamas, J. C. Carre-
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Angewandte
Chemie
tero, J. Org. Chem. 2003, 68, 3679 – 3686; c) J. Priego, O. García
Mancheæo, S. Cabrera, R. Gómez Arrayµs, T. Llamas, J. C.
Carretero, Chem. Commun. 2002, 2512 – 2513.
[5] a) M. Lautens, S. Hiebert, J. Am. Chem. Soc. 2004, 126, 1437 –
1447; b) M. Lautens, S. Hiebert, J.-L. Renaud, J. Am. Chem. Soc.
2001, 123, 6834 – 6839; c) M. Lautens, S. Hiebert, J.-L. Renaud,
Org. Lett. 2000, 2, 1971 – 1973; d) M. Lautens, J.-L. Renaud, S.
Hiebert, J. Am. Chem. Soc. 2000, 122, 1804 – 1805. For a review
on enantioselective metal-catalyzed opening reactions of oxabi-
cyclic alkenes, see: M. Lautens, K. Fagnou, S. Hiebert, Acc.
Chem. Res. 2003, 36, 48 – 58.
[6] According to the participation of cationic palladium species, it
has been recently reported that the cationic m-hydroxo complex
[{Pd((R)-binap)-(m-OH)}2]2+(OTfÀ)2 is much more effective than
the currently used dichloro complex, see reference [5a] (binap =
2,2’-bis(diphenylphosphanyl)-1,1’-binaphthyl, Tf = trifluorome-
thanesulfonyl).
[7] For the use of the parent ligands 1 in the Pd-catalyzed
desymmetrization of oxabenzonorbornadiene, see referen-
ce [4c].
[8] For achiral cationic methyl P,S-palladium complexes, see: a) O.
Daugulis, M. Brookhart, P. S. White, Organometallics 2002, 21,
5935 – 5943; b) G. P. Suranna, P. Mastrorilli, C. F. Nobile, W.
Keim, Inorg. Chim. Acta 2000, 305, 151 – 156.
[9] Crystal structure for C27H30ClFePPdS [(1a)Pd(Cl)(Me)]: crystal
size 0.35 ” 0.34 ” 0.32mm, hexagonal, space group P61, a =
18.3144(2), b = 18.3144(2), c = 15.7573(2) Š, g = 1208, V=
4577.18(9) Š3, Z = 6, 1calcd = 1.339 MgmÀ3
, ,
m = 10.583 mmÀ1
2qmax = 70.258, CuKa radiation, l = 1.54178 Š, 2q/w scans, T=
296(2) K, absorption correction: none, 29638 reflections col-
lected, 5709 independent. Refinement on F2 for 5709 reflections
and 293 parameters gave GOF = 0.996, R1 = 0.0334, wR2 =
0.0992for I > 2s(I). Residual electron density À0.391 < D1 <
0.775 eŠÀ3. Absolute structure parameter À0.008(5).
[10] M. Brookhart, M. Wagner, J. Am. Chem. Soc. 1994, 116, 3641 –
3642.
[11] Crystal structure for C66H47BF24FeNPPdS {[(1a)Pd(Me)(NC-
Ph)]+[(ArF )B]À}: crystal size 0.23 ” 0.14 ” 0.10 mm, monoclinic,
4
space group P21, a = 17.372(3), b = 23.423(4), c = 18.140(3) Š,
b = 110.615(3)8, V= 6909(2) Š3, Z = 4, 1calcd = 1.487 MgmÀ3, m =
0.628 mmÀ1, 2qmax = 56.568, MoKa radiation, l = 0.71073 Š, 2q/
w scans, T= 293 K, absorption correction: none, 24303 reflec-
tions collected, 10937 independent. Refinement on F2 for 24303
reflections and 1739 parameters gave GOF = 1.002, R1 = 0.0895,
wR2 = 0.2353 for I > 2s(I). Residual electron density À1.655 <
À3
D1 < 0.944 eŠ
.
Absolute structure parameter À0.01(3).
CCDC-231878 and CCDC-229828 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or
from the Cambridge Crystallographic Data Centre, 12Union
Road, Cambridge CB21EZ, UK; fax: (+ 44)1223-336-033; or
deposit@ccdc.cam.ac.uk).
[12] The absolute configuration of the alcohols 2–4 and 6a was
established by comparison with the data obtained by HPLC
using a chiral stationary phase for both enantiomers of these
compounds (see references [5c] and [5d]).
[13] In all these reactions the enantioselectivity achieved from
[(1e)Pd(Cl)(Me)] was significantly higher than that from the
parent diphenylphosphanyl catalyst [(1a)Pd(Cl)(Me)].
[14] A higher reactivity was found in DCE than in toluene, probably
as a result of the increased solubility of the cationic Pd complex
in the former.
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