C2-symmetric diphosphine ligands with only the planar chirality of ferrocene for the palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1021/jo9902998

Novel C₂-symmetric diphosphine ligands possessing only the planar chirality of ferrocene, 1,1'-bis(diphenylphosphino)-2,2'-disubstituted- ferrocenes, were prepared from 1,1'-bis(diphenylphosphino)-2,2'- bis(oxazolinyl)ferrocene by the transform

Full text of DOI:10.1021/jo9902998

J . Org. Chem. 1999, 64, 6247-6251
6247
C2-Sym m etr ic Dip h osp h in e Liga n d s w ith On ly th e P la n a r
Ch ir a lity of F er r ocen e for th e P a lla d iu m -Ca ta lyzed Asym m etr ic
Allylic Alk yla tion
Wanbin Zhang, Takashi Shimanuki, Toshiyuki Kida, Yohji Nakatsuji, and Isao Ikeda*
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, J apan
Received February 17, 1999
Novel C2-symmetric diphosphine ligands possessing only the planar chirality of ferrocene, 1,1′-
bis(diphenylphosphino)-2,2′-disubstituted-ferrocenes, were prepared from 1,1′-bis(diphenylphos-
phino)-2,2′-bis(oxazolinyl)ferrocene by the transformation of the oxazoline moieties in the molecule.
Upon complexation with palladium(II), ligands of this kind were ascertained to form only one of
1
the two possible diastereomeric 1:1 P,P-chelating palladium complexes by H NMR spectroscopy
using NOE. These ligands afforded excellent enantioselectivity for the palladium-catalyzed allylic
alkylation of 1,3-diphenylprop-2-en-1-yl acetate with dimethyl malonate. The substituents at the
2,2′-positions of the Cp rings of the ligands had considerable effect on the catalytic activity but
minor effect on the enantioselectivity. These ligands also afforded excellent catalytic activity and
good enantioselectivity for the allylic alkylation of the less sterically hindered substrate, cyclohex-
2-en-1-yl acetate, with dimethyl malonate. It has been shown that the C2-symmetric ferrocene
ligands with only the planar chirality can produce an excellent chiral environment for metal-
catalyzed asymmetric reactions.
In tr od u ction
ferrocene ligands with only planar chirality until now.5
As a part of our studies on the development of novel
oxazoline ligands with multistereogenic centers,4,6 we
recently reported a simple preparation of novel C2-
symmetric ferrocene diphosphine ligands, 1,1′-bis(diphen-
ylphosphino)-2,2′-bis(oxazolinyl)ferrocenes 1 (Chart 1),
via highly diastereoselective ortho-lithiation of the cor-
responding bis(oxazolinyl)ferrocenes.4a However, ligands
of this kind also possess the central chirality at the
oxazoline rings along with the planar chirality of fer-
rocene and did not form the expected P,P-chelating
complex with dichlorobis(acetonitrile)palladium, although
Chiral diphosphines have been proved to be among the
most useful and versatile ligands for metal-catalyzed
asymmetric reactions, and the design and preparation
of such diphosphines remain as active an area of research
as ever.1 Meanwhile, the planar chirality of ferrocene has
received intensive attention, and many kinds of planar
chiral ferrocene ligands have been developed recently.2-4
However, most of the ferrocene ligands also possess
central chirality besides the planar chirality, and no
efficient ferrocene ligands with only the planar chirality
have been developed so far. Moreover, C2-symmetric
chiral ferrocene ligands have recently gained some at-
tention,3,4 but there has been no report on C2-symmetric
(3) (a) Hayashi, T.; Yamamoto, A.; Hojo, M.; Ito, Y. J . Chem. Soc.,
Chem. Commun. 1989, 495-496. (b) Hayashi, T.; Yamamoto, A.; Hojo,
M.; Kishi, K.; Ito, Y.; Nishioka, E.; Miura, H.; Yanagi, K. J . Organomet.
Chem. 1989, 370, 129-139. (c) Park, J .; Lee, S.; Ahn, K. H.; Cho, C.-
H. Tetrahedron Lett. 1995, 36, 7263-7267. (d) Schwink, L.; Knochel,
P. Tetrahedron Lett. 1996, 37, 25-28. (e) Park, J .; Lee, S.; Ahn, K. H.;
Cho, C.-H. Tetrahedron Lett. 1996, 37, 6137-6140. (f) Enders, D.;
Lochtman, R. Synlett 1997, 355-356. (g) Ahn, K. H.; Cho, C.-H.; Park,
J .; Lee, S. Tetrahedron: Asymmetry 1997, 8, 1179-1185. (h) Perea, J .
J . A.; Borner, A.; Knochel, P. Tetrahedron Lett. 1998, 39, 8073-8076.
(4) (a) Zhang, W.; Adachi, Y.; Hirao, T.; Ikeda, I. Tetrahedron:
Asymmetry 1996, 7, 451-460. (b) Zhang, W.; Hirao, T.; Ikeda, I.
Tetrahedron Lett. 1996, 37, 4545-4548.
(1) (a) Rajanbabu, T. V.; Casalnuovo, A. L. J . Am. Chem. Soc. 1996,
118, 6325-6326. (b) Reetz, M. T.; Beuttenmuller, E. W.; Goddard, R.
Tetrahedron Lett. 1997, 38, 3211-3214. (c) Zhu, G.; Cao, P.; J iang,
Q.; Zhang, X. J . Am. Chem. Soc. 1997, 119, 1799-1800. (d) Pye, J . P.;
Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J . J .
Am. Chem. Soc. 1997, 119, 6207-6208. (e) Pye, P. J .; Rossen, K.;
Reamer, R. A.; Volante, R. P.; Reider, P. J . Tetrahedron Lett. 1998,
39, 4441-4444. (f) J iang, Q.; J iang, Y.; Xiao, D.; Cao, P.; Zhang, X.
Angew. Chem., Int. Ed. Engl. 1998, 37, 1100-1103.
(2) For reviews, see: (a) Hayashi, T. In Ferrocenes; Togni, A.,
Hayashi, T., Eds., VCH: Weinheim, 1995; pp 105-142. (b) Richards,
C. J .; Locke, A. J . Tetrahedron: Asymmetry 1998, 9, 2377-2407. For
recent examples, see: (c) Richards, C. J .; Mulvaney, A. W. Tetrahedron:
Asymmetry 1996, 7, 1119-1130. (d) Nishibayashi, Y.; Segawa, K.;
Arikawa, Y.; Ohe, K.; Hidai, M.; Uemura, S. J . Organomet. Chem. 1997,
546-547, 381-398. (e) Sammakia, T.; Stangeland, E. L. J . Org. Chem.
1997, 62, 6104-6105. (f) Enders, D.; Peters, R.; Lochtman, R.; Runsink,
J . Synlett 1997, 1462-1464. (g) Lagneau, N. M.; Chen, Y.; Robben, P.
M.; Sin, H.-S.; Takasu, K.; Chen, J .-S.; Robinson, P. D.; Hua, D. H.
Tetrahedron 1997, 54, 7301-7334. (h) Chesney, A.; Bryce, M.; Chubb,
R. W. J .; Batsanov, A. S.; Howard, J . A. K. Synthesis 1998, 413-416.
(i) Schwink, L.; Knochel, P. Chem. Eur. J . 1998, 4, 950-968. (j) Riant,
O.; Argouarch, G.; Guillaneux, D.; Samuel, O.; Kagan, H. B. J . Org.
Chem. 1998, 63, 3511-3514. (k) Bolm, C.; Muniz-Fernandez, K.; Seger,
A.; Raabe, G.; Gunther, K. J . Org. Chem. 1998, 63, 7860-7867. (l)
Torre, F. G.; J alon, F. A.; Lopez-Agenjo, A.; Manzano, B. R.; Rodriguez,
A.; Sturm, T.; Weissensteiner, W.; Martinez-Ripoll, M. Organometallics
1998, 17, 4634-4644.
(5) After a part of our work reported here was communicated,7
several papers concerning the preparation of C2-symmetric ferrocene
derivatives with only the planar chirality appeared: (a) J endralla, H.;
Paulus, E. Synlett 1997, 471-472. (b) Kang J .; Lee, J . H.; Ahn, S. H.;
Choi, J . S. Tetrahedron Lett. 1998, 39, 5523-5526. (c) Iftime, G.; Daran,
J .-C.; Manoury, E.; Balavoine, G. G. A. Angew. Chem., Int. Ed. Engl.
1998, 37, 1698-1701. (d) Iftime, G.; Daran, J .-C.; Manoury, E.;
Balavoine, G. G. A. J . Organomet. Chem. 1998, 565, 115-124. (e)
Zhang, W.; Yoneda, Y.; Kida, T.; Nakatsuji, Y.; Ikeda, I. J . Organomet.
Chem. 1999, 574(1), 19-23.
(6) (a) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron: Asymmetry 1996, 7, 2453-2462. (b) Imai, Y.; Zhang, W.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron Lett. 1997, 38, 2681-
2684. (c) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Tetrahedron Lett. 1998, 39, 4343-4346. (d) Zhang, W.; Yoneda, Y.;
Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron: Asymmetry 1998, 9,
3371-3380. (e) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I.
Chem. Lett. 1999, 243-244. (f) Imai, Y.; Zhang, W.; Kida, T.; Nakatsuji,
Y.; Ikeda, I. Synlett 1999, 1319-1321.
10.1021/jo9902998 CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/05/1999

6248 J . Org. Chem., Vol. 64, No. 17, 1999
Zhang et al.
Ch a r t 1
Sch em e 1
they showed excellent enantioselectivity for the pal-
ladium-catalyzed allylic alkylation.4b In this paper, we
report the preparation of C2-symmetric P,P-chelating
ligands with only the planar chirality of ferrocene 2a -e
(Chart 1) and their application in asymmetric reactions.7
Palladium-catalyzed asymmetric C-C bond forming
reactions with allylic compounds have been investigated
with great intensity.8 Particularly, the palladium-cata-
lyzed allylic alkylation of 1,3-diphenylprop-2-en-1-yl ac-
etate with dimethyl malonate has received considerable
attention,8-10 and excellent enantioselectivities have been
documented with N,N- and P,N-chelating ligands.9 How-
ever, few P,P-chelating ligands, especially with C2-
symmetry, gave excellent results.10 Compared to 1,3-
diphenylprop-2-en-1-yl acetate, the less sterically hindered
substrates, pent-3-en-2-yl acetate11 and cyclohex-2-en-1-
yl acetate,12 have received little attention, and few chiral
ligands gave excellent results for these substrates. With
novel C2-symmetric planar chiral P,P-chelating ligands
2 in hand, we carried out these reactions and examined
the effects of the sole planar chirality and the substitu-
ents at the 2,2′-positions of the Cp rings on the enanti-
oselectivity and the catalytic activity.
Resu lts a n d Discu ssion
Ligands 2a -c can be easily prepared from 1a 4a by the
transformation of the oxazoline moieties in the molecule
by Meyer’s method (Scheme 1).13 Thus, treatment of 1a
with trifluoroacetic acid in aqueous THF caused ring-
opening of the oxazoline moiety to give an unstable
ammonium salt. This ammonium salt was acetylated,
without isolation, with acetic anhydride in the presence
of pyridine to give ester amide 3 in 61% yield. Transes-
terification of 3 using methanolic sodium methoxide at
room temperature for 1 day gave ligand 2a in 74% yield.
Ligands 2b,c were also prepared from 3 by a similar
procedure, but in lower yields due to the lower reactivities
of sodium ethoxide and sodium isopropoxide than that
of sodium methoxide.
(7) As the first report on C2-symmetric ferrocene ligands with only
planar chirality, a part of this work has been communicated; see:
Zhang, W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. Tetrahedron Lett. 1996,
37, 7995-7998.
(8) For reviews, see: (a) Frost, C. G.; Howarth, J .; Williams, J . M.
J . Tetrahedron: Asymmetry 1992, 3, 1089-1122. (b) Hayashi, T. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993;
pp 325-365. (c) Reiser, O. Angew. Chem., Int. Ed. Engl. 1993, 32, 547-
549. (d) Trost, B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395-
422. (e) Ghosh, A. K.; Mathivanan, P.; Cappiello, J . Tetrahedron:
Asymmetry 1998, 9, 1-45.
It has been reported that the hydroxyl group in several
P,P-chelating ligands have some effect on the enantiose-
lectivity.14 With this idea in mind, we designed diphos-
phine ligands 2d and 2e, each of which possesses two
hydroxyl groups in the molecule.
In our previous paper on the preparation of novel
bisoxazoline ligands bearing a 1,3-dioxolane backbone,
we reported that N-(2-hydroxy-1-substituted-ethyl)amide
intermediates can be prepared equivalently with ease by
heating 4,5-dicarbonyl-1,3-dioxolane dimethyl ester with
the corresponding chiral 2-amino alcohol in neat at 100
°C for 1 h.6a However, 2d and 2e could not be obtained
by the same method even by heating methyl ester 2a with
2-aminoethanol or 3-aminopropanol at 120 °C for 2 days.
However, we found that heating 2a with 2-amino-
ethanol or 3-aminopropanol in neat in the presence of a
small amount of sodium at 100 °C for 30 min afforded
2d and 2e, respectively, in good yields (Scheme 2).
Next, the complexation behavior of ligand 2a with
palladium dichloride was examined. Because of the
(9) Selected papers for N,N-chelating ligands: (a) Pfaltz, P. Acc.
Chem. Res. 1993, 26, 339-345. (b) Kubota, H.; Nakajima, M.; Koga,
K. Tetrahedron Lett. 1993, 34, 8135-8138. (c) Kang, J .; Cho, W. O.;
Cho, H. G. Tetrahedron: Asymmetry 1994, 5, 1347-1352. (d) Hoarao,
O.; Ait-Haddou, H.; Castro, M.; Balavoine, G. G. A. Tetrahedron:
Asymmetry 1997, 8, 3755-3764. (e) Bremberg, U.; Rahm, F.; Moberg,
C. Tetrahedron: Asymmetry 1998, 9, 3437-3443. Selected papers for
P,N-chelating ligands: (f) Sprinz, J .; Helmchen, G. Tetrahedron Lett.
1993, 34, 1769-1772. (g) Matt, P.-V.; Pfalts, A. Angew. Chem., Int.
Ed. Engl. 1993, 32, 566-568. (h) Dawson, G. J .; Frost, C. G.; Williams,
J . M. J .; Coote, S. J . Tetrahedron Lett. 1993, 34, 3149-3150. (i) Brown,
J . M.; Hulmes, D. I.; Guiry, P. J . Tetrahedron 1994, 50, 4493-4506.
(j) Kubota, H.; Koga, K. Tetrahedron Lett. 1994, 35, 6689-6692. (k)
Wimmer, P.; Widhalm, M. Tetrahedron: Asymmetry 1995, 6, 657-660.
(l) Togni, A.; Burckhardt, U.; Gramlich, V.; Pregosin, P. S.; Salzmann,
R. J . Am. Chem. Soc. 1996, 118, 1031-1037. (m) Mino, T.; Imiya, W.;
Yamashita, M. Synlett 1997, 583-584. (n) Cahill, J . P.; Guiry, P. J .
Tetrahedron: Asymmetry 1998, 9, 4301-4305. (o) Vyskocil, S.; Smrcina,
M.; Hanus, V.; Polasek, M.; Kocovsky, P. J . Org. Chem. 1998, 63, 7738-
7748. (p) Gilbertson, S. R.; Chang, C.-W. T. J . Org. Chem. 1998, 63,
8424-8431.
(10) (a) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron
Lett. 1986, 27, 191-194. (b) Yamaguchi, M.; Shima, T.; Yamagishi,
T.; Hida, M. Tetrahedron: Asymmetry 1991, 2, 663-666. (c) Pregosin,
P. S.; Ruegger, H.; Salzmann, R.; Albinati, A.; Lianza, F.; Kunz, R. W.
Organometallics 1994, 13, 83-90. (d) Dierkes, P.; Ramdeehul, S.;
Barloy, L.; Cian, A. D.; Fischer, J .; Kamer, P. C. J .; Leeuwen, P. W. N.
M.; Osborn, J . A. Angew. Chem., Int. Ed. Engl. 1998, 37, 3116-3118.
(11) (a) Allen, J . V.; Coote, S. J .; Dawson, G. J .; Frost, C. G.; Martin,
C. J .; William, J . M. J . J . Chem. Soc., Perkin Trans. 1 1994, 2065-
2072. (b) Trost, B. M.; Breit, B.; Peukert, S.; Zambrano, J .; Ziller, J .
W. Angew. Chem., Int. Ed. Engl. 1995, 34, 2386-2388. Also see refs
3g, 9c, 9g, 9o, and 10d.
(12) (a) Togni, A. Tetrahedron: Asymmetry 1991, 2, 683-690. (b)
Trost, B. M.; Bunt, R. C. J . Am. Chem. Soc. 1994, 116, 4089-4090. (c)
Sennhenn, P.; Gabler, B.; Helmchen, G. Tetrahedron Lett. 1994, 35,
8595-8598. (d) Knuhl, G.; Sennhenn, P.; Helmchen, G. J . Chem. Soc.,
Chem. Commun. 1995, 1845-1846. (e) Kudis, S.; Helmchen, G. Angew.
Chem., Int. Ed. Engl. 1998, 37, 3047-3050. Also see refs 9c, 9i, and
10d.
(13) (a) Warshawsky, A. M.; Meyer, A. I. J . Am. Chem. Soc. 1990,
112, 8090-8099. (b) Nelson, T. D.; Meyer, A. I. J . Org. Chem. 1994,
59, 2655-2658.
(14) For a review, see: Holz, J .; Quirmbach, M.; Borner, A. Synthesis
1997, 983-1006.

C2-Symmetric Diphosphine Ligands
J . Org. Chem., Vol. 64, No. 17, 1999 6249
Ta ble 1. P d -Ca ta lyzed Allylic Alk yla tion of 5a
Sch em e 2
entry
ligand
baseb
T (°C)
time (h)
ee (%)c
1
2
3
4
5
6
7
8
9
2a
2b
2c
3
2d
2e
2a
2a
2a
2c
3
BSA
BSA
BSA
BSA
BSA
BSA
NaH
BSA
BSA
BSA
BSA
25
25
25
25
25
25
25
0
1
3
8
10
5
3
1
7
72
10
68
86
91
92
91
88
89
84
90
88
94
94
Ch a r t 2. Deter m in a tion of Com p lex Str u ctu r e by
NOE (%)
-25
10
11
0
0
a
1 mmol of 5, 3 mmol of dimethyl malonate, 3 mmol of base,
30 µmol of ligand, and 12.5 µmol of [Pd(η3-C3H5)Cl]2 in 3 mL of
CH2Cl2. Product was isolated in above 90% yields except for entries
b
9 (45%), 10 (63%), and 11 (61%). When BSA was used, 20 µmol
of KOAc was added. c Determined by HPLC (Chiralcel OD).
opposite twists of the two Cp rings of the ferrocene
backbone, 2a would give two possible diastereomeric
complexes, 4a and 4b, upon complexation with palladium
dichloride (Chart 2). However, the formation of only one
kind of C2-symmetric 1:1 P,P-chelating complex was
found in 1H NMR upon mixing 2a with 1 equiv of di-
chlorobis(acetonitrile)palladium(II) in acetonitrile-d3.
Treating 2a with 1 equiv of dichlorobis(acetonitrile)-
palladium(II) in benzene for 1 h followed by filtration
gave the complex as a yellow solid in 97% yield. Recrys-
tallization of the complex from dichloromethane-hexane
provided orange prismatic crystals, which contain one
molecule of dichloromethane per complex as determined
by 1H NMR and elemental analysis. We attempted to
determine the structure of the complex by the single-
crystal X-ray analysis, but failed. Therefore, the com-
lectivity.8d In this case, however, there is no great dif-
ference between NaH and N,O-bis(trimethylsilyl)acet-
amide (BSA) used as the base (entries 1 and 7). The
reaction temperature has a considerable influence on the
reaction rate. At room temperature, the reaction pro-
ceeded fast and completed within 1 h with either BSA
or NaH as a base when 2a was used (entries 1 and 7).
Lowering the temperature decreased the reaction rate
(entries 8-11). At -25 °C, the reaction was very slow
and only 45% yield was obtained after 72 h (entry 9). The
reaction temperature also has some influence on the
enantioselectivity (entries 8-11), and up to 94% ee was
attained at 0 °C with 2c and 3 (entries 10 and 11). This
is one of the best results reported so far for the allylic
alkylation of 1,3-diphenylprop-2-en-1-yl acetate using C2-
symmetric P,P-chelating ligands.10
1
plex structure was examined by H NMR spectroscopy
using the nuclear Overhauser enhancement (NOE).
NOEs were observed between Ha and Hb, Ha and Hc,
methyl and Ha, and methyl and Hc, respectively (Chart
2). No obvious NOE was observed between methyl and
Hb. On the basis of this finding, the complex can be
assigned to be 4a .
The palladium-catalyzed allylic alkylation of 1,3-diphen-
ylprop-2-en-1-yl acetate (5) with dimethyl malonate using
novel C2-symmetric planar chiral P,P-chelating ligands
2 and their precursor 3 was carried out and the results
are shown in Table 1.
It was seen that all of the ligands show good to
excellent enantioselectivity and the ligand structures
have some effect on the enantioselectivity and the
catalytic activity. From the results with 2a -c it was
found that the bulkier the ester group is, the higher the
enantioselectivity is, but the lower the catalytic activity
becomes (entries 1-3). Compound 3, which is the precur-
sor of ligands 2 and has the bulkiest ester groups,
afforded almost the same ee with 2b and 2c, but the
lowest catalytic activity (entry 4). Ligands 2d and 2e
have been expected to exert a positive effect on the
enantioselectivity for this allylic alkylation by the inter-
action between the hydroxyl groups in the ligand and the
substrate. In fact, no higher ee than those of 2b, 2c, and
3 was obtained (entries 5 and 6).
It should be interesting to know whether these chiral
ligands are effective for other less sterically hindered
allylic substrates. So, the palladium-catalyzed allylic
alkylation of cyclohex-2-en-1-yl acetate (7) with dimethyl
malonate was carried out, and the results are shown in
Table 2.
Compared to that of 1,3-diphenylprop-2-en-1-yl acetate
(5), ligand 2a showed an excellent catalytic activity for
the palladium-catalyzed allylic alkylation of cyclohex-2-
en-1-yl acetate (7) with BSA as a base, and all the
products could be isolated in above 90% yields. At 25 and
0 °C, the reaction was extremely rapid and completed
within 10 min (entries 1 and 2). Lowering the reaction
temperature decreased the reaction rate (entries 3 and
4), but even at -50 °C, the reaction also proceeded fast
and could completed within 1 h (entry 4). Ligand 2a also
afforded good enantioselectivity for the allylic alkylation,
and the reaction temperature has some influence on the
enantioselectivity. At 25 °C, 75% ee was obtained for
product 8 (entry 1), while lowering the reaction temper-
ature to -50 °C afforded up to 83% ee (entry 4). Similarly
rapid reaction and good enantioselectivity were observed
with NaH as a base instead of BSA (entries 1 and 6).
The ligand structure has some influence on the enantio-
selectivity. Ligand 2b, which has bulkier ester groups
than ligand 2a , afforded a little lower enantioselectivity
than 2a (entries 2 and 7). This result is different from
It was reported that in many cases the base used in
this reaction has a significant effect on the enantiose-

6250 J . Org. Chem., Vol. 64, No. 17, 1999
Zhang et al.
Ta ble 2. P d -Ca ta lyzed Allylic Alk yla tion of 7a
dichloromethane (20 mL) were added pyridine (3.6 mL, 44.5
mmol) and acetic anhydride (6.0 mL, 38.2 mmol), and the
mixture was stirred at room temperature overnight. The
mixture was washed with 1 N HCl, water, and then brine and
dried over Na2SO4. After removal of the solvent, the residue
(2.01 g) obtained was purified by silica gel column chroma-
tography with ethyl acetate as an eluent to afford pure ester
amide 3 as a yellow solid (0.54 g, 61% overall yield from 1a ).
Mp 102-104 °C. [R]25 ) -437.4 (c 0.34, CHCl3). 1H NMR
589
entry
ligand
baseb
T (°C)
time
ee (%)c
(600 MHz, CDCl3): δ 1.02 (6H, d, J 6.5 Hz), 1.07 (6H, d, J 6.5
Hz), 1.88 (6H, s), 2.08 (2H, m), 3.45 (2H, br s), 3.95 (2H, dd, J
7.3, 11.5 Hz), 4.13 (2H, m), 4.41 (2H, dd, J 2.6, 11.5 Hz), 5.06
(2H, br s), 4.66 (2H, br s), 6.59 (2H, d, J 8.8 Hz), 7.12 (4H, m),
7.22 (8H, m), 7.29 (8H, m). IR (KBr, cm-1): 1714, 1658, 1529.
FABMS: m/z 897 ([M + 1]+).
1
2
3
2a
2a
2a
2a
2a
2a
2b
BSA
BSA
BSA
BSA
BSA
NaH
BSA
25
0
-25
-50
-25
25
<10 min
<10 min
20 min
1 h
1 h
<10 min
<10 min
75
81
82
83
81
74
77
4
5d
6
(-)-(S )-(S )-1,1′-B i s (d i p h e n y lp h o s p h i n o )-2,2′-b i s -
(m et h oxyca r bon yl)fer r ocen e (2a ). To a solution of ester
amide 3 (0.50 g, 0.558 mmol) in THF (10 mL) was added a
sodium methoxide solution prepared by the addition of sodium
metal (0.513 g, 22.3 mmol) to methanol (35 mL). After being
stirred for 24 h, the mixture was neutralized with methanolic
acetic acid, and the solvent was removed by evaporation. The
residue was dissolved in dichloromethane (60 mL), and the
solution was washed with water and then brine and dried over
MgSO4. After removal of the solvent, the residue was purified
by silica gel column chromatography with ethyl acetate as an
eluent to afford 2a as a yellow solid (0.28 g, 74%). Mp 198 °C
7
0
a
1 mmol of 7, 3 mmol of dimethyl malonate, 3 mmol of base,
30 µmol of ligand, and 12.5 µmol of [Pd(η3-C3H5)Cl]2 in 3 mL of
CH2Cl2. Product was isolated in above 90% yields except for entry
b
5 (80%). When BSA was used, 20 µmol of KOAc was added.
d
c Determined by HPLC (Chiralcel OB-H). 12 µmol of ligand and
5.0 µmol of [Pd(η3-C3H5)Cl]2 were used.
Sch em e 3
dec. [R]25
) -595.2 (c 0.25, CHCl3). 1H NMR (400 MHz,
589
CDCl3): δ 3.48 (2H, br s), 3.74 (6H, s), 4.56 (2H, t, J 2.7 Hz),
5.09 (2H, br s), 7.14-7.31 (20H, m). 31P NMR (CDCl3,
P(OCH3)3): δ -160.28. IR (KBr, cm-1): 1707. FABMS: m/z
670 (M+). HRMS (EI): calcd for C38H32O4P2Fe 670.1127, found
670.1115. Anal. Calcd for C38H32O4P2Fe: C, 67.91; H, 4.95.
Found: C, 68.08; H, 4.81.
that of the allylic alkylation of 1,3-diphenylprop-2-en-1-
yl acetate (5) with ligands 2a and 2b.
(-)-(S)-(S)-1,1′-Bis(d ip h en ylp h osp h in o)-2,2′-b is(et h -
oxyca r bon yl)fer r ocen e (2b). Following a procedure identical
to that described for the preparation of 2a , the reaction of 3
(0.16 g, 0.185 mmol) in THF (6 mL) with a sodium ethoxide
solution prepared by the addition of sodium metal (0.30 g,
13.04 mmol) to ethanol (20 mL) for 48 h afforded 2b as a yellow
Ligand 2a also showed excellent catalytic activity for
the palladium-catalyzed allylic alkylation of pent-3-en-
2-yl acetate (9) with dimethyl malonate (Scheme 3). The
reaction proceeded very fast with BSA as a base at 0 °C
and was completed within 10 min. Only 12% ee, however,
was obtained for product 10.
solid (0.055 g, 43%). Mp 207 °C dec. [R]25 ) -454.0 (c 0.50,
589
1
CHCl3). H NMR (400 MHz, CDCl3): δ 1.20 (6H, t, J 7.1 Hz),
3.46 (2H, br s), 4.11-4.20 (2H, m), 4.25-4.33 (2H, m), 4.66
Con clu sion
(2H, t, J 2.4 Hz), 5.08 (2H, br s), 7.12-7.31 (20H, m). 31P NMR
(CDCl3, P(OCH3)3):
δ
-160.28. IR (KBr, cm-1): 1712.
In summary, we have prepared the first C2-symmetric
diphosphine ligands 2 possessing only the planar chiral-
ity of ferrocene from 1,1′-bis(diphenylphosphino)-2,2′-bis-
(oxazolinyl)ferrocene 1 by the transformation of the
oxazoline moieties in the molecule. With this new kind
of C2-symmetric chiral diphosphine ligands and their
precursor 3, the palladium-catalyzed allylic alkylations
of 1,3-diphenylprop-2-en-1-yl acetate and cyclohex-2-en-
1-yl acetate with dimethyl malonate were carried out,
and up to 94% ee and 83% ee were afforded for products
6 and 8, respectively. These results show that the C2-
symmetric ferrocene ligands with only the planar chiral-
ity can produce an excellent asymmetric environment for
metal-catalyzed asymmetric reactions.
FABMS: m/z 698 (M+). HRMS (EI): calcd for C40H36O4P2Fe
698.1440, found 698.1425. Anal. Calcd for C40H36O4P2Fe‚
0.25H2O: C, 68.34; H, 5.23. Found: C, 68.28; H, 5.40.
(-)-(S)-(S)-1,1′-Bis(d ip h en ylp h osp h in o)-2,2′-bis(isop r o-
p oxyca r bon yl)fer r ocen e (2c). Following a procedure identi-
cal to that described for the preparation of 2a , the reaction of
3 (0.19 g, 0.223 mmol) in THF (6 mL) with
a sodium
isopropoxide solution prepared by the addition of solid sodium
(0.36 g, 15.7 mmol) to 2-propanol (30 mL) for 20 h afforded 2c
1
as a yellow solid (0.028 g, 17%). Mp 200 °C dec. H NMR (400
MHz, CDCl3): δ 1.12 (6H, d, J 6.2 Hz), 1.30 (6H, d, J 6.2 Hz),
3.45 (2H, br s), 4.72 (2H, t, J 2.6 Hz), 5.05 (2H, br s), 5.10
(2H, m), 7.12-7.30 (20H, m). 31P NMR (CDCl3, P(OCH3)3): δ
-160.28. IR (KBr, cm-1): 1712. FABMS: m/z 727 ([M + 1]+).
HRMS (EI): calcd for C42H40O4P2Fe 726.1753, found 726.1769.
(-)-(S)-(S)-1,1′-Bis(d ip h en ylp h osp h in o)-2,2′-b is[N-(2-
h yd r oxyeth yl)a m id o]fer r ocen e (2d ). A mixture of 2a (0.090
g, 0.134 mmol), 2-aminoethanol (1 mL, 16.6 mmol), and a small
amount of sodium was heated at 100 °C for 30 min. The
mixture was diluted with dichloromethane (20 mL) and
neutralized with acetic acid. The neutralized solution was
washed with water and then with brine and dried over
Na2SO4. After removal of the solvent, the residue was purified
by silica gel column chromatography with acetone as an eluent
Exp er im en ta l Section
Gen er a l Meth od s. Complete descriptions of the apparatus
have recently been published.6d Compound 1 was prepared
according to the method reported before.4a
P r ep a r a tion of th e Ester Am id e 3 in Sch em e 1. To a
solution of compound 1a (0.77 g, 0.99 mmol) in THF (20 mL)
were added water (1 mL), trifluoroacetic acid (1.9 mL, 24.7
mmol), and Na2SO4 (9.40 g), and this suspension was stirred
overnight at room temperature. After filtration and removal
of the solvent under reduced pressure at below room temper-
ature, an unstable ester ammonium salt was obtained as a
brown solid. To a solution of this ester ammonium salt in
to afford 2d as a yellow solid (0.066 g, 68%). Mp 116-117 °C.
1
[R]25 ) -336.9 (c 0.49, CHCl3). H NMR (400 MHz, CDCl3):
589
δ 3.48-3.57 (8H, m), 3.80 (4H, q), 4.39 (2H, t, J 2.9 Hz), 5.00
(2H, br s), 7.00-7.53 (22H, m). 31P NMR (CDCl3, P(OCH3)3):
δ -162.58. IR (KBr, cm-1): 3400, 1633, 1538. FABMS: m/z

C2-Symmetric Diphosphine Ligands
J . Org. Chem., Vol. 64, No. 17, 1999 6251
729 ([M + 1]+). Anal. Calcd for C40H38N2O4P2Fe‚H2O: C, 64.35;
H, 5.40; N, 3.75. Found: C, 64.43; H, 5.41; N, 3.79.
(-)-(S)-(S)-1,1′-Bis(d ip h en ylp h osp h in o)-2,2′-b is[N-(3-
h yd r oxylp r op yl)a m id o]fer r ocen e (2e). Following a proce-
dure identical to that described for the preparation of 2d , the
reaction of 2a (0.050 g, 0.075 mmol), 3-aminopropanol (0.77
mL, 10.1 mmol), and a small amount of sodium at 80 °C for
added to a mixture of 5 (0.252 g, 1.00 mmol) and potassium
acetate (0.002 g, 20 µmol) in dry dichloromethane (2 mL) via
a cannula, followed by the addition of dimethyl malonate
(0.396 g, 3.00 mmol) and BSA (0.613 g, 3.00 mmol). When NaH
was used as a base instead of BSA, the catalyst solution was
added to a mixture of acetate 5 (0.252 g, 1.00 mmol) and
dimethyl sodiummalonate prepared from dimethyl malonate
(0.396 g, 3.00 mmol) and NaH (72% in Nujol, 0.100 g, 3.00
mmol). The reactions were carried out at room temperature
and monitored by TLC for the disappearance of 5 (5, Rf ) 0.42;
6, Rf ) 0.30; solvent, hexane-ethyl acetate, 3:1). When 5
disappeared, the solvent was evaporated and the resulting
mixture was extracted with ether (50 mL). The extract was
washed twice with ice-cold saturated NH4Cl aqueous solution
(50 mL) and then dried over Na2SO4. After removal of the
ether, the residue was purified on silica gel column chroma-
tography with hexane-ethyl acetate (3:1) to afford pure
product 6.
30 min afforded 2e as a yellow solid (0.046 g, 82%). Mp 85-
1
86 °C. [R]25 ) -371.1 (c 1.44, CHCl3). H NMR (400 MHz,
589
CDCl3): δ 3.40 (2H, br s), 3.52 (4H, q, J 5.9 Hz), 3.64-3.77
(8H, m), 4.38 (2H, t, J 2.6 Hz), 4.96 (2H, br s), 7.10-7.54 (22H,
m). 31P NMR(CDCl3, P(OCH3)3): δ -162.58. IR (KBr, cm-1):
3330, 1629, 1540. FABMS: m/z 757 ([M + 1]+). Anal. Calcd
for C42H42N2O4P2Fe‚1.25H2O: C, 64.75; H, 5.76; N, 3.60.
Found: C, 64.57; H, 5.69; N, 3.49.
Com p lexa tion Beh a vior of 2a w ith Dich lor obis(a ceto-
n itr ile)p a lla d iu m . Compound 2a (6.9 mg, 0.01 mmol) was
dissolved in acetonitrile-d3 (0.40 mL) to give solution A, and
dichlorobis(acetonitrile)palladium (8.0 mg, 0.03 mmol) was
dissolved in acetonitrile-d3 (1.50 mL) to give solution B.
Addition of 0.25 mL of solution B (0.005 mmol) to solution A
gave a solution containing 2a and a C2-symmetric 1:1 complex,
(-)-(S)-Dim eth yl (1,3-Diph en ylpr op-2-en -1-yl)m alon ate
1
(6). H NMR (400 MHz, CDCl3): δ 3.52 (3H, s), 3.70 (3H, s),
3.93 (1H, d, J 10.7 Hz), 4.27 (1H, dd, J 8.8, 10.7 Hz), 6.30 (1H,
dd, J 15.8, 8.8 Hz), 6.44 (1H, d, J 15.8 Hz), 7.19-7.32 (10H,
m). The enantiomeric excess was determined by HPLC analy-
sis at 25 °C [Chiralcel OD, 25 cm × 0.46 cm; hexane:2-propanol
1
4 ([2a ]PdCl2), judging from the H NMR analysis. When 0.50
mL of solution B (0.01 mmol) was added, compound 2a
disappeared, and only complex 4 was formed as determined
by 1H NMR analysis. The addition of more than 0.5 mL of
solution B gave the same result as above and did not produce
) 99.5:0.5; flow rate 0.9 mL/min; tR ) 19.8 min ((R)-6), tR
21.1 min ((S))-6)].
)
(+)-(R)-Dim eth yl (Cycloh ex-2-en -1-yl)m a lon a te (8).1H
NMR (400 MHz, CDCl3): δ 1.38 (1H, m), 1.58 (1H, m), 1.68-
1.83 (2H, m), 1.96-2.03 (2H, m), 2.92 (1H, m), 3.30 (1H, d, J
9.6 Hz), 3.74 (3H, s), 3.75 (3H, s), 5.53 (1H, m), 5.79 (1H, m).
The enantiomeric excess was determined by HPLC analysis
at 40 °C [Chiralcel OB-H, 25 cm × 0.46 cm; hexane:2-propanol
) 90:10; flow rate 0.5 mL/min; tR ) 13.2 min ((R)-8), tR ) 17.1
min ((S)-8)].
1
a new complex. H NMR (400 MHz, CD3CN): δ 3.35 (6H, s),
4.30 (2H, br s), 4.63 (2H, br s), 4.86 (2H, br s), 7.25-7.39 (12H,
m), 8.01 (4H, dd, J 7.0, 11.2 Hz), 8.25 (4H, dd, J 7.3, 11.5 Hz).
For comparison with 4, the 1H NMR data of ligand 2a in
CD3CN were determined. 1H NMR (400 MHz, CD3CN): δ 3.47
(2H, br s), 3.69 (6H, s), 4.55 (2H, t, J 2.6 Hz), 5.06 (2H, br s),
7.11 (4H, m), 7.28 (14H, m), 7.35 (2H, m).
(-)-(S)-Dim eth yl (P en t-3-en -2-yl)m a lon a te (10).1H NMR
(400 MHz, CDCl3): δ 1.07 (3H, d, J 7.0 Hz), 1.64 (3H, dd, J
6.2, 1.5 Hz), 2.91 (1H, m), 3.27 (1H, d, J 9.2 Hz), 3.70 (3H, s),
3.74 (3H, s), 5.35 (1H, m), 5.53 (1H, m). The enantiomeric
excess was determined by comparison of its specific rotation
P r ep a r a tion of Com p lex 4. A suspension of 2a (33.5 mg,
0.05 mmol) and dichlorobis(acetonitrile)palladium (13.0 mg,
0.05 mmol) in dry benzene (2 mL) was stirred under argon for
1 h to produce a precipitate. After filtration, 4 (41.2 mg, 97%)
was obtained as a yellow solid. Recrystallization of 4 from
dichloromethane-hexane provided orange prismatic crystals,
which contain one molecule of dichloromethane per complex
as determined by 1H NMR and elemental analysis. Mp 236
value with a literature value9g [[R]23 ) -3.3 (c 1.1, CHCl3);
589
12% ee].
1
°C dec. H NMR (400 MHz, CDCl3): δ 3.35 (6H, s), 4.29 (2H,
Ack n ow led gm en t. Financial support from the Min-
istry of Education, Science and Culture, J apan (Grant-
in-Aid for Scientific Research on Priority Area Nos.
09238231 and 10132238) is gratefully acknowledged. We
thank Sumitomo Chemical Co., Ltd. for assistance in
the ee determination of 8. We are grateful to Mrs.
Toshiko Muneishi and Mrs. Yoko Miyaji at the Analyti-
cal Center, Faculty of Engineering, Osaka University,
for their assistance in the NMR spectroscopic deter-
mination.
br s), 4.49 (2H, t, J 2.7 Hz), 4.81 (2H, br s), 5.30 (2H, s), 7.40
(12H, m), 8.11 (4H, m), 8.25 (4H, m). 31P NMR(CDCl3,
P(OCH3)3): δ -95.69. IR (KBr, cm-1): 1720. FABMS: m/z 848
([M + 1]+). Anal. Calcd for C38H32O4P2FePdCl2‚CH2Cl2: C,
50.22; H,3.67. Found: C, 50.08; H, 3.63.
Gen er a l P r oced u r e for P a lla d iu m -Ca t a lyzed Allylic
Alk yla tion . The reaction of 1,3-diphenylprop-2-en-1-yl acetate
(5) is illustrative of the general method for all catalytic
reactions described in this study. A mixture of ligand 2a (20.1
mg, 30 µmol) and [Pd(η3-C3H5)Cl]2 (4.6 mg, 12.5 µmol) in dry
dichloromethane (1 mL) was stirred at room temperature
under argon for 1 h, and the resulting yellow solution was
J O9902998