Asymmetric synthesis of metallocenes through enantioselective addition of organolithium reagents to 6-(dimethylamino)fulvene

Article abstract of DOI:10.1021/jo0111199

Enantioselective addition of aryllithiums 2a-d (Ar = Ph (a), 2-MeC₆H₄ (b), 2-MeOC₆H₄ (c), 1-naphthyl (d)) to 6-(dimethylamino)fulvene (1) in the presence of (-)-sparteine in toluene at -78°C generated chiral cyclopentadienyllithiums (4) substituted with an N,N-dimethylamino(aryl)methyl group, where the enantioselectivities are 51, 91, 90, and 83% for 4a, 4b, 4c, and 4d, respectively. Treatment of the chiral cyclopentadienides 4 with FeCl₂ or Fe(acac)₂ gave ferrocenes, which contain an N,N-dimethylamino(aryl)methyl side chain on both of the cyclopentadienyl rings. The enantiomeric purity of the chiral ferrocenes 7 thus obtained is 99% ee or higher for those containing a 2-MeC₆H₄ (7b) or a 2-MeOC₆H₄ (7c) group.

Full text of DOI:10.1021/jo0111199

J . Org. Chem. 2002, 67, 3355-3359
3355
Asym m etr ic Syn th esis of Meta llocen es th r ou gh En a n tioselective
Ad d ition of Or ga n olith iu m Rea gen ts to 6-(Dim eth yla m in o)fu lven e
Toshimasa Suzuka, Masamichi Ogasawara, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, J apan
thayashi@kuchem.kyoto-u.ac.jp
Received December 3, 2001
Enantioselective addition of aryllithiums 2a -d (Ar ) Ph (a ), 2-MeC6H4 (b), 2-MeOC6H4 (c),
1-naphthyl (d )) to 6-(dimethylamino)fulvene (1) in the presence of (-)-sparteine in toluene at -78
°C generated chiral cyclopentadienyllithiums (4) substituted with an N,N-dimethylamino(aryl)-
methyl group, where the enantioselectivities are 51, 91, 90, and 83% for 4a , 4b, 4c, and 4d ,
respectively. Treatment of the chiral cyclopentadienides 4 with FeCl2 or Fe(acac)2 gave ferrocenes,
which contain an N,N-dimethylamino(aryl)methyl side chain on both of the cyclopentadienyl rings.
The enantiomeric purity of the chiral ferrocenes 7 thus obtained is 99% ee or higher for those
containing a 2-MeC6H4 (7b) or a 2-MeOC6H4 (7c) group.
Sch em e 1
In tr od u ction
It is well documented that enantiomerically enriched
ferrocene derivatives are powerful chiral auxiliaries in
asymmetric reactions.1 Of the chiral ferrocene auxiliaries,
chiral ferrocenylphosphines have been used most widely
and successfully as chiral ligands for transition metal-
catalyzed asymmetric reactions including hydrogenation,
allylic alkylation, cross-coupling, and aldol-type reac-
tions.2,3 One of the unique features of the ferrocene-based
chiral auxiliaries is that most of them possess the
ferrocene planar chirality, which is usually introduced
by the diastereoselective ortho-lithiation of ferrocenes
containing an N,N-dimethylamino group at the R-position
of the chiral side chain4 or some other chiral ortho-
directing groups.5 A typical example is N,N-dimethyl-1-
ferrocenylethylamine,6 which is a key intermediate for
the preparation of several types of chiral ferrocenylphos-
phines, ppfa,2,7 bppfa,2,7 trap,8 josiphos,9 and so on.1,3 The
ferrocenes containing an N,N-dimethylamino group at
the R stereogenic carbon center have been obtained by
optical resolution of the racemate6 or by way of optically
active alcohols prepared by asymmetric reduction of
ketones10 or asymmetric alkylation of ferrocenecarbox-
aldehyde11 (Scheme 1). Togni reported another useful
method for their preparation through generation of a
chiral cyclopentadienyllithium by diastereoselective ad-
dition of methyllithium to a fulvene substituted with a
chiral amino group.12 Here we report an enantioselective
version of the asymmetric addition, which is practically
useful for the preparation of chiral ferrocenes (90% ee)
containing N,N-dimethylamino and aryl groups at the R
stereogenic carbon center.
* To whom correspondence should be addressed. Fax: 81-75-753-
3988.
(1) For reviews on chiral ferrocene derivatives, see: (a) Richards,
C. J .; Locke, A. J . Tetrahedron: Asymmetry 1998, 9, 2377. (b) Hayashi,
T. In Ferrocenes; Togni, A., Hayashi, T., Eds.; VCH: Weinheim,
Germany, 1995; pp 105-142.
(2) (a) Hayashi, T.; Kumada, M. Acc. Chem. Res. 1982, 15, 395. (b)
Hayashi, T. Pure Appl. Chem. 1988, 60, 7.
(3) For books on catalytic asymmetric reactions, see: (a) Ojima, I.
Catalytic Asymmetric Synthesis, 2nd ed.; VCH: New York, 2000. (b)
J acobsen, E. N.; Pfaltz, A.; Yamamoto, H. Comprehensive Asymmetric
Catalysis; Springer: Berlin, 1999; Vols. 1-3. (c) No´gra´di, M. Stereo-
selective Synthesis; VCH: New York, 1995. (e) Seyden-Penne, J . Chiral
Auxiliaries and Ligands in Asymmetric Synthesis; Wiley: New York,
1995. (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994.
(4) Wagner, G.; Herrmann, R. In Ferrocenes; Togni, A., Hayashi,
T., Eds.; VCH: Weinheim, Germany, 1995; pp 173-218.
(5) (a) Rebie`re, F.; Riant, O.; Ricard, L.; Kagan, H. B. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 568. (b) Riant, O.; Samuel, O.; Kagan, H. B. J .
Am. Chem. Soc. 1993, 115, 5835. (c) Richards, C. J .; Damalidis, T.;
Hibbs, D. E.; Hursthouse, M. B. Synlett 1995, 74. (d) Sammakia, T.;
Latham, H. A.; Schaad, D. R. J . Org. Chem. 1995, 60, 10. (e)
Nishibayashi, Y.; Uemura, S. Synlett 1995, 79.
(6) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann, P.; Ugi, I.
J . Am. Chem. Soc. 1970, 92, 5389.
(7) (a) Hayashi, T.; Yamamoto, K.; Kumada, M. Tetrahedron Lett.
1974, 4405. (b) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.;
Nagashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi,
M.; Yamamoto, K.; Kumada, M. Bull. Chem. Soc. J pn. 1980, 53, 1138.
(8) Sawamura, M.; Hamashima, H.; Ito, Y. Tetrahedron: Asymmetry
1991, 2, 593.
(9) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.;
Tijani, A. J . Am. Chem. Soc. 1994, 116, 4062.
(10) (a) Schwink, L.; Knochel, P. Tetrahedron Lett. 1996, 37, 25. (b)
Almena Perea, J . J .; Bo¨rner, A.; Knochel, P. Tetrahedron Lett. 1998,
39, 8073. (c) Schwink, L.; Knochel, P. Chem. Eur. J . 1998, 4, 950. (d)
Almena Perea, J . J .; Lotz, M.; Knochel, P. Tetrahedron: Asymmetry
1999, 10, 375.
(11) (a) Matsumoto, Y.; Ohno, A.; Lu, S.-J .; Hayashi, T.; Oguni, N.;
Hayashi, M. Tetrahedron: Asymmetry 1993, 4, 1763. (b) Soai, K.;
Hayase, T.; Takai, K.; Sugiyama, T. J . Org. Chem. 1994, 59, 7908.
(12) Abbenhuis, H. C. L.; Burckhardt, U.; Gramlich, V.; Togni, A.;
Albinati, A.; Mu¨ller, B. Organometallics 1994, 13, 4481.
10.1021/jo0111199 CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/05/2002

3356 J . Org. Chem., Vol. 67, No. 10, 2002
Suzuka et al.
Ta ble 1. Asym m etr ic Ad d ition of Ar yllith iu m 2 to
Sch em e 2
6-(Dim eth yla m in o)fu lven e (1) in th e P r esen ce of Ch ir a l
Liga n d 3a
temp time
product 5
entry ArLi 2 ligand 3
(°C)
(h)
yield (%)b
% eec
1
2
3
4
5
6
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2c
2d
3m
3m
3m
3n
-78
-70
-40
-78
-78
-78
-78
-78
-78
-78
-78
-78
-78
7
7
7
7
7
7
7
7
7
7
7
15
7
5a
93
99
99
51
54
92
86
82
81
77
92
83
92
51 (R)
42 (R)
25 (R)
62 (R)
23 (S)
91 (R)
0 (R)
23 (R)
8 (R)
20 (R)
10 (R)
90 (R)
83 (R)
5a
5a
5a
5a
5b
5b
5b
5b
5b
5b
5c
5d
3o
3m
3m
3m
3m
3n
3o
3m
3m
7d
8e
9f
10
11
12
13
a
Reaction was carried out with 1 (0.40 mmol) and aryllithium
2 (0.48 mmol) in the presence of a chiral ligand 3 (0.48 mmol) in
1.0 mL of toluene at a given temperature, and then [RhCl(nbd)]2
b
(0.48 mmol Rh) was added at -78 °C. Isolated yield of rhodium
complex 5 by column chromatography on alumina (8/1 hexane/
ethyl acetate). c Enantiomeric purity was determined by HPLC
analysis with a chiral stationary phase column (Chiralcel OD-H,
100/1 hexane/2-propanol for 5a and 5b, 200/1 for 5c, and 300/1
for 5d ). Absolute configurations of 5a and 5b were determined by
correlation with ferrocenes 7a and 7b (see text). For 5c and 5d ,
configurations were assigned by consideration of similarity of the
d
reaction pathway. In THF. e In the presence of lithium bromide.
f In the presence of 20 mol % (-)-sparteine (3m ).
Resu lts a n d Discu ssion
lectivity obtained with 2-methylphenyllithium (2b), the
results summarized in Table 1 contain several significant
features. (1) The enantioselectivity is high (over 90%) for
the reaction of aryllithiums 2b and 2c, which contain
ortho-substituents (entries 6 and 12). The addition of
2-methoxyphenyllithium also proceeded with high enan-
tioselectivity (90% ee), though the reaction is slow (entry
11). (2) Sparteine (3m )16,17 is more effective than chiral
bisoxaoline 3n and diether 3o especially for the reaction
of 2-methylphenyllithium (2b) (entries 6, 10, and 11). (3)
The use of toluene as a solvent is important for the high
enantioselectivity, the reaction in THF giving the racemic
product (entry 7).18 (4) Lithium bromide, generated at the
preparation of aryllithiums from aryl bromides and
lithium metal, must be removed for the high enantiose-
lectivity (entry 8). (5) The enantioselectivity is higher at
lower reaction temperatures (entries 1-3). (6) Unfortu-
nately, the asymmetric addition requires a stoichiometric
amount of the chiral base, the use of a catalytic amount
of sparteine under the present reaction conditions giving
the addition product with much lower enantioselectivity
(entry 9).
For the asymmetric addition of an aryllithium 2 to
6-(dimethylamino)fulvene (1)13 forming lithium cyclopen-
tadienide (4) substituted with an N,N-dimethylamino-
(aryl)methyl group, several reaction conditions were
examined for high enantioselectivity and high yield. The
cyclopentadienide 4 was converted to a cyclopentadienyl-
rhodium(I) 5 by treatment with [RhCl(norbornadiene)]2
(Scheme 2), because the reaction-forming rhodium com-
plex 5 is fast at a low temperature and analysis of its
enantiomeric purity is easy with HPLC equipped with a
chiral stationary-phase column. A typical reaction pro-
cedure is shown for the addition of 2-methylphenyl-
lithium (2b) in the presence of (-)-sparteine (3m ) (entry
6 in Table 1). To a solution of (-)-sparteine (3m ) (0.48
mmol) in toluene was added, at -78 °C, a cyclohexane/
ether (1/1) solution of 2-methylphenyllithium (2b) (0.48
mmol), which was prepared from 2-methylphenyl bro-
mide and lithium metal and made free from lithium
bromide. A solution of 6-(dimethylamino)fulvene (1) (0.40
mmol) in toluene was added, and the mixture was stirred
at -78 °C for 7 h. At the same temperature was added
[RhCl(norbornadiene)]2 (0.48 mmol Rh), and the whole
mixture was stirred at room temperature for 12 h.
Aqueous workup followed by chromatography on alumina
gave 92% yield of cyclopentadienylrhodium(I) complex
5b, which is an (R)-isomer of 91% ee. The R configuration
was determined by correlation with known chiral fer-
rocene (R,R)-7b10b,14 (vide infra). The enantioselectivity
observed here is much higher than the 17% ee reported
for the asymmetric reduction of 6-methyl-6-phenylfulvene
that is only one precedent of enantioselective reaction of
fulvene derivatives.15 In addition to the high enantiose-
The cyclopentadienyllithiums 4, which were generated
by the enantioselective addition of aryllithiums 2 in the
presence of (-)-sparteine at -78 °C, were used for the
(15) Leblanc, J . C.; Moise, C. J . Organomet. Chem. 1976, 120, 65.
(16) For reviews related to the use of sparteine for asymmetric
reactions of organolithium reagents: (a) Beak, P.; Basu, A.; Gallagher,
D. J .; Park, Y. S.; Thayumanavan, S. Acc. Chem. Res. 1996, 29, 552.
(b) Beak, P.; Anderson, D. R.; Curtis, M. D.; Laumer, J . M.; Pippel, D.
J .; Weisenburger, G. A. Acc. Chem. Res. 2000, 33, 715.
(17) For a review on the asymmetric reaction of organolithium
reagents coordinated with chiral ligands such as 3m -o, see: Tomioka,
K.; Nagaoka, Y. In Comprehensive Asymmetric Catalysis; J acobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 3,
Chapter 31.1.
(13) Hafner, K.; Vo¨pel, K. H.; Ploss, G.; Ko¨nig, C. In Organic
Syntheses; Baumgarten, H. E., Ed.; Wiley: New York, 1973; Col. Vol.
5, p 431.
(14) The optical rotations for (R,R)-7a and (R,R)-7b were measured
as a mixture with the corresponding meso isomers 8. See Experimental
Section.
(18) The higher enantioselectivity in toluene than in THF has been
observed, for example, in the asymmetric alkylation of a benzyllithium
coordinated with (-)-sparteine: Wu, S.; Lee, S.; Beak, P. J . Am. Chem.
Soc. 1996, 118, 715.

Asymmetric Synthesis of Metallocenes
J . Org. Chem., Vol. 67, No. 10, 2002 3357
Sch em e 3
Sch em e 5
Sch em e 4
(entry 1). The enantiomeric purities of chiral ferrocenes
(R,R)-7b and (R,R)-7c resulting from the asymmetric
addition of 2-methylphenyllithium (2b) and 2-methoxy-
phenyllithium (2c), respectively, are extremely high (99%
ee or higher) as it is expected from the calculation based
on 90-91% ee of cyclopentadienyllithiums 4b and 4c
(entries 2 and 3).
The mixture of (R,R)-7b (>99% ee) and 8b (88:12 ratio),
obtained by the reaction shown in entry 2 in Table 2, was
subjected to the ortho-lithiation with butyllithium in
ether followed by treatment of the dilithiated ferrocene
with 1,2-dibromotetrafluoroethane to give, after silica gel
chromatography, 60% isolated yield (based on 7b) of
dibromide (R,R,SFc,SFc)-9b as a diastereomerically pure
product. The dibromide 9b is a useful synthetic inter-
mediate to chiral ferrocene derivatives represented by C2-
symmetric chiral bisphosphines.10
Ta ble 2. Asym m etr ic Syn th esis of F er r ocen e 7 by
Asym m etr ic Ad d ition of Ar yllith iu m 2 to
6-(Dim eth yla m in o)fu lven e (1) in th e P r esen ce of
(-)-Sp a r tein e (3m ) F ollow ed by Tr ea tm en t w ith F eCl2 or
a
F e(a ca c)2
results
calculationb
yieldc of 7 ratio of
% eed
of 7
ratio of
7:8
% ee
of 7
entry ArLi 2 and 8 (%)
7:8
1
2a
2b
2c
2d
99
94
80
68
63:37
78 (R,R) 63:37 80 (R,R)
99.6 (R,R)
99 (R,R) 90:10 99.4 (R,R)
85:11 98 (R,R)
2
88:12 >99 (R,R) 91:9
90:10
92:8
3e
4
f
Con clu sion
a
Aryllithium 2 was added to 1 in the presence of (-)-sparteine
(3m ) at -78 °C. The cyclopentadienyllithium 4 generated was
added to a THF solution of FeCl2. Calculation was made on the
basis of enantiomeric purities of 51, 91, 90, and 83% ee for 4a ,
4b, 4c, and 4d , respectively, obtained from data shown in Table
1. c Isolated yield by silica gel chromatography (5/4/1 hexane/Et2O/
We have described the first successful example of
enantioselective addition to a fulvene generating a chiral
cyclopentadienide anion, which was realized in the reac-
tion of aryllithiums with 6-(dimethylamino)fulvene in the
presence of (-)-sparteine. The chiral cyclopentadienyl-
lithiums were efficiently transferred onto iron(II) giving
ferrocenes substituted with an N,N-dimethylamino group
at the R position of the side chain. The enantiomeric
excesses of the ferrocenes are very high, up to 91% ee
for those containing one chiral side chain and 99% ee or
higher for those containing two chiral side chains, one
on each of the cyclopentadienyl rings. The chiral fer-
rocenes obtained here are versatile synthetic intermedi-
ates that can be converted into various types of chiral
ferrocene derivatives through diastereoselective ortho-
lithiation.1,2,10
b
d
Et3N). Determined by HPLC analysis with a chiral stationary
phase column (Chiralcel OD-H, 100/1/0.1 hexane/2-propanol/
triethylamine). Fe(acac)2 was used in place of FeCl2. f Not deter-
e
mined.
asymmetric synthesis of ferrocene derivatives (Schemes
3 and 4). Thus, treatment of 4b with FeCp*(acac) (Cp*
) pentamethylcyclopentadienyl), which is generated in
situ from Fe(acac)2 and Cp*Li,12,19 gave 95% yield of
ferrocene 6b. Its enantiomeric purity as determined by
HPLC analysis was 93%, essentially the same as that of
the rhodium complex 5b, indicating that the enantio-
meric purity of the cyclopentadienide 4b is transferred
to rhodium(I) and iron(II) without loss of its purity at
the substitution reaction with the electrophiles.
Exp er im en ta l Section
The reaction of 4 with FeCl2 or Fe(acac)2 gave high
yields of ferrocenes containing the chiral side chain on
both cyclopentadienyl rings. As expected, the ferrocenes
consist of chiral and meso isomers 7 and 8, respectively.
The ratio of 7 to 8 and the enantiomeric excess of the
chiral isomer 7 obtained here are in good agreement with
the values calculated from the enantiomeric excess of the
cyclopentadienyllithium 4 on the assumption that both
enantiomers of 4 are statistically incorporated into the
ferrocene (Table 2). Thus, cyclopentadienyllithium 4a
(51% ee) generated by the asymmetric addition of phe-
nyllithium 2a gave (R,R)-7a 14 of 78% ee and 8a in a ratio
of 63:37, the calculated values being 80% ee and 63:37
Gen er a l. All manipulations were carried out under a
nitrogen atmosphere. Nitrogen gas was dried by passage
through P2O5. Chemical shifts for NMR spectra are reported
in δ parts per million referenced to an internal tetramethyl-
silane standard for 1H NMR and chloroform-d (δ 77.0) for 13C
NMR.
Ma ter ia ls. Rhodium complex [RhCl(norbornadiene)]220 and
6-(dimethylamino)fulvene (1)13 were prepared according to the
reported procedures. Phenyllithium (2a ) in cyclohexane/ether
(1/1) was purchased commercially.
P r ep a r a tion of Ar yllith iu m s. 2-Methylphenyllithium (2b)
and 2-methoxyphenyllithium (2c) were prepared from the
corresponding aryl bromides and lithium metal in ether under
standard procedures.21 To the ether solution was added an
equivalent volume of cyclohexane, and the white powder of
(19) Bunel, E. E.; Valle, L.; Manriquez, J . M. Organometallics 1985,
4, 1680.
(20) Schrock, R. R.; Osborn, J . A. J . Am. Chem. Soc. 1971, 93, 2397.
(21) J ones, R. G.; Gilman, H. Org. React. 1951, 6, 339.

3358 J . Org. Chem., Vol. 67, No. 10, 2002
Suzuka et al.
precipitated lithium bromide was removed by filtration through
a glass wool plug.
1-Naphthyllithium (2d ) was generated by lithiation of
1-bromonaphthalene with n-butyllithium in ether.
2.5 Hz), 56.55 (d, J ) 6.6 Hz), 66.44, 82.45 (d, J ) 4.1 Hz),
82.74 (d, J ) 4.1), 85.62 (d, J ) 4.1 Hz), 86.32 (d, J ) 4.1 Hz),
110.21 (d, J ) 4.6 Hz), 124.10, 124.34, 125.18, 125.29, 126.91,
128.84, 131.67, 134.08, 142.29. Anal. Calcd for C25H26NRh: C,
67.72; H, 5.91. Found: C, 67.76; H, 5.89. [R]20 -219 (c 0.3,
Asym m etr ic Ad d ition of Ar yllith iu m 2 to 6-(Dim eth y-
la m in o)fu lven e (1). (A) Rea ction of th e Cyclop en ta d ien -
id e 4 w ith [Rh Cl(n bd )]2. The reaction conditions and results
are summarized in Table 1. A typical procedure is given for
the reaction of 2-methylphenyllithium (2b) in the presence of
(-)-sparteine (3m ) giving [1-(dimethylamino)-1-(2-methylphe-
nyl)methyl-η5-cyclopentadienyl](η4-norbornadiene)rhodium (Rh-
[η5-C5H4CH(NMe2)(2-MeC6H4)](nbd), 5b) (entry 6 in Table 1).
To a solution of (-)-sparteine (112 mg, 0.48 mmol) in dry
toluene (0.8 mL) was added a solution of 2-methylphenyl-
lithium (0.74 M in cyclohexane/ether (1/1), 0.64 mL, 0.48 mmol)
at -78 °C. After the solution was stirred at room temperature
for 10 min and then cooled to -90 °C, a solution of 6-(dim-
ethylamino)fulvene (1, 48.4 mg, 0.40 mmol) in dry toluene (0.2
mL) was added dropwise over 10 min. The reaction mixture
was stirred at -78 °C for 7 h, and then [RhCl(nbd)]2 (109 mg,
0.48 mmol Rh) was added. The reaction mixture was stirred
at room temperature for 12 h, and then water (5 mL) was
added. The mixture was extracted with ether. The combined
extracts were washed with saturated aqueous sodium chloride
and dried over anhydrous magnesium sulfate. The solvent was
evaporated, and the residue was chromatographed on alumina
(8/1 hexane/ethyl acetate) to give a mixture of 5b and a
considerable amount of (-)-sparteine. Removal of (-)-sparteine
by distillation under reduced pressure gave 161.5 mg (92%
yield) of Rh[η5-C5H4CH(NMe2)(2-MeC6H4)](nbd) (5b).
D
CHCl3) for (R)-5d of 83% ee. Chiral HPLC conditions: Chiral-
cel OD-H, 300/1 hexane/2-propanol.
(B) Rea ction of th e Cyclop en ta d ien id e 4b w ith F e-
(a ca c)2 a n d Lith iu m P en ta m eth ylcyclop en ta d ien id e. To
a stirred brown suspension of Cp*Fe(acac) (prepared in situ
from [Fe(acac)2]n (780 mg, 3.1 mmol) and LiCp* (3.1 mmol) in
10 mL of THF)17 was added, at 0 °C, a solution of lithium
cyclopentadienide 4b (which was generated in situ from
6-(dimethylamino)fulvene (1) (375 mg, 3.1 mmol) in toluene
(5 mL) and 2-methylphenyllithium (2b) (5.0 mL, 3.7 mmol) in
the presence of (-)-sparteine (3m ) (865 mg, 3.7 mmol)). The
resulting green suspension was stirred for 1 h at room
temperature and then poured into ca. 20 mL of water. The
reaction mixture was extracted with ether. The combined
extracts were washed with water and dried over anhydrous
magnesium sulfate. The solvent was evaporated and the
residue was chromatographed on silica gel (hexane/diethyl
ether/triethylamine ) 5/4/1) to give 1.18 g (95% yield) of Fe-
[η5-C5H4CH(NMe2)(2-MeC6H4)](η5-C5Me5) (6b).
Spectral and analytical data for the ferrocene 6b are shown
below. F e[η5-C5H4CH(NMe2)(2-MeC6H4)](η5-C5Me5) (6b): 1H
NMR (CDCl3) δ 1.82 (s, 15H), 2.17 (s, 6H), 2.51 (s, 3H), 3.37
(s, 1H), 3.57 (s, 1H), 3.63 (s, 1H), 4.01 (s, 1H), 5.00 (s, 1H),
7.01 (d, J ) 7.0 Hz, 1H), 7.09 (t, J ) 7.0 Hz, 1H), 7.13 (t, J )
7.0 Hz, 1H), 7.17 (d, J ) 7.0, 1H); 13C NMR (CDCl3) δ 9.32,
11.03, 20.56, 42.12, 62.42, 70.51, 70.60, 71.67, 72.24, 79.86,
124.86, 126.48, 130.21, 130.50, 133.68, 136.59. Anal. Calcd for
Spectral and analytical data for the rhodium complexes 5
are shown below. Rh [η5-C5H4CH(NMe2)P h ](n bd ) (5a ): 1H
NMR (CDCl3) δ 0.80 (s, 2H), 2.13 (s, 6H), 2.67 (s, 2H), 2.77 (s,
2H), 3.06 (s, 2H), 3.69 (s, 1H), 4.93 (s, 1H), 5.13 (s, 1H), 5.21
(s, 2H), 7.22 (t, J ) 7.5 Hz, 1H), 7.32 (t, J ) 7.5 Hz, 2H), 7.45
(d, J ) 7.5 Hz, 2H); 13C NMR (CDCl3) δ 28.19 (d, J ) 10.2
Hz), 29.33 (d, J ) 10.2 Hz), 44.86, 46.17 (d, J ) 2.5 Hz), 56.87
(d, J ) 6.7 Hz), 71.65, 82.07 (d, J ) 4.7 Hz), 84.09 (d, J ) 4.1
Hz), 85.54 (d, J ) 4.1 Hz), 86.46 (d, J ) 4.1 Hz), 108.53 (d, J
) 5.2 Hz), 126.69, 127.85, 127.93, 144.85. Anal. Calcd for
C
25H33NFe: C, 74.44; H, 8.25. Found: C, 74.40; H, 8.45. [R]20
D
+89 (c 0.56, CHCl3) for (R)-6b of 93% ee. Chiral HPLC
conditions: Chiralcel OD-H, 100/1 hexane/2-propanol.
(C) Rea ction of th e Cyclop en ta d ien id e 4 w ith F eCl2
Givin g F er r ocen e 7. The reaction conditions and results are
summarized in Table 2. A typical procedure is given for the
reaction of 2-methylphenyllithium (2b) in the presence of (-)-
sparteine (3m ) giving 1,1′-bis[1-(dimethylamino)-1-(2-meth-
ylphenyl)methyl]ferrocenes, Fe[η5-C5H4CH(NMe2)(2-MeC6H4)]2,
7b and 8b (entry 2 in Table 2). To a solution of (-)-sparteine
(2.10 g, 9.0 mmol) in dry toluene (10 mL) was added a solution
of 2-methylphenyllithium (0.74 M in cyclohexane/ether (1/1),
12 mL, 9.0 mmol) at -78 °C. After the solution was stirred at
room temperature for 10 min and cooled to -90 °C, a solution
of 6-(dimethylamino)fulvene (1) (907 mg, 7.5 mmol) in dry
toluene (4 mL) was added dropwise at -90 °C over 10 min.
The reaction mixture was stirred at -78 °C for 7 h, and the
reaction mixture was added to a suspension of FeCl2 (562 mg,
4.4 mmol) in dry THF via cannula. The mixture was stirred
at room temperature for 12 h, and water (10 mL) was added.
The mixture was extracted with ether. The combined extracts
were washed with aqueous sodium chloride solution and dried
over anhydrous magnesium sulfate. The solvent was evapo-
rated, and the residue was chromatographed on silica gel (5/
4/1 hexane/ether/triethylamine) to give 1.72 g (94% yield) of a
mixture of (R,R)-Fe[η5-C5H4CH(NMe2)(2-MeC6H4)]2 (7b) and
meso-Fe[η5-C5H4CH(NMe2)(2-MeC6H4)]2 (8b) in a ratio of 88:
12.
C
21H24NRh: C, 64.13; H, 6.15. Found: C, 63.87; H, 6.07. [R]20
D
+57 (c 1.0, CHCl3) for (R)-5a of 51% ee. Chiral HPLC
conditions: Chiralcel OD-H, 100/1 hexane/2-propanol. Rh [η5-
C5H4CH(NMe2)(2-MeC6H4)](n bd ) (5b): 1H NMR (CDCl3) δ
0.78 (s, 2H), 2.11 (s, 6H), 2.46 (s, 2H), 2.62 (s, 3H), 2.87 (s,
2H), 3.03 (s, 2H), 4.02 (s, 1H), 4.87 (s, 1H), 4.93 (s, 1H), 5.13
(s, 1H), 5.38 (s, 1H), 7.09 (t, J ) 7.8 Hz, 1H), 7.18 (m, 2H),
7.61 (d, J ) 7.8 Hz, 1H); 13C NMR (CDCl3) δ 20.53, 28.94 (d,
J ) 10.3 Hz), 29.42 (d, J ) 10.3 Hz), 44.99, 46.20 (d, J ) 2.6
Hz), 56.86 (d, J ) 6.6 Hz), 66.01, 81.89 (d, J ) 4.1 Hz), 82.57
(d, J ) 4.1 Hz), 85.57 (d, J ) 4.1 Hz), 86.96 (d, J ) 3.6 Hz),
109.60 (d, J ) 4.6 Hz), 125.73, 126.17, 126.52, 130.08,
135.18, 144.09. Anal. Calcd for C22H26NRh: C, 64.87; H, 6.43.
Found: C, 64.84; H, 6.44. [R]20 +45 (c 1.0, CHCl3) for (R)-5b
D
of 91% ee. Chiral HPLC conditions: Chiralcel OD-H, 100/1
hexane/2-propanol. Rh [η5-C5H4CH(NMe2)(2-MeOC6H4)](n bd)
(5c): 1H NMR (CDCl3) δ 0.78 (s, 2H), 2.12 (s, 6H), 2.70 (s,
2H), 2.74 (s, 2H), 3.02 (s, 2H), 3.88 (s, 3H), 4.36 (s, 1H), 4.90
(s, 1H), 5.17 (s, 1H), 5.23 (s, 1H), 5.28 (s, 1H), 6.87 (d, J ) 7.4
Hz, 1H), 6.95 (t, J ) 7.4 Hz, 1H), 7.18 (t, J ) 7.4 Hz, 1H), 7.59
(d, J ) 7.4, 1H); 13C NMR (CDCl3) δ 28.73 (d, J ) 6.6 Hz),
28.81 (d, J ) 6.6 Hz), 44.54, 46.16 (d, J ) 2.5 Hz), 55.33, 56.79
(d, J ) 6.7 Hz), 61.01, 81.93 (d, J ) 4.1 Hz), 83.98 (d, J ) 4.1
Hz), 85.18 (d, J ) 4.1 Hz), 87.29 (d, J ) 4.1 Hz), 107.93 (d, J
) 5.1 Hz), 110.31, 120.35, 127.32, 128.14, 132.86, 156.34. Anal.
Calcd for C22H26NORh: C, 62.42; H, 6.19. Found: C, 62.55;
Spectral and analytical data for the ferrocene derivatives 7
and
8
are shown below. (R,R)-F e[η5-C5H 4CH (NMe2)(2-
MeC6H4)]2 (7b): 1H NMR (CDCl3) δ 1.96 (s, 12H), 2.55 (s, 6H),
3.21 (s, 2H), 3.51 (s, 2H), 3.73 (s, 2H), 3.81 (s, 2H), 3.87 (s,
2H), 7.15-7.25 (m, 4H), 7.26 (t, J ) 7.7 Hz, 2H), 7.49 (d, J )
7.7 Hz, 2H); 13C NMR (CDCl3) δ 20.73, 44.48, 66.18, 66.82,
67.34, 69.92, 71.32, 90.96, 126.05, 126.54, 127.55, 130.06,
134.87, 142.55. Anal. Calcd for C30H36N2Fe: C, 74.99; H, 7.55.
Found: C, 74.77; H, 7.55 (a mixture of isomers 7b and 8b).
H, 6.28. [R]20 +10 (c 1.0, CHCl3) for (R)-5c of 90% ee. Chiral
D
HPLC conditions: Chiralcel OD-H, 200/1 hexane/2-propanol.
Rh [η5-C5H4CH(NMe2)(1-n a p h th yl)](n bd ) (5d ): 1H NMR
(CDCl3) δ 0.53 (s, 2H), 2.11 (s, 2H), 2.19 (s, 6H), 2.39 (s, 2H),
2.64 (s, 2H), 4.66 (s, 1H), 4.91 (s, 1H), 4.98 (s, 1H), 5.13 (s,
1H), 5.31 (s, 1H), 7.46-7.49 (m, 2H), 7.52 (t, J ) 8.1 Hz, 1H),
7.59 (t, J ) 8.1 Hz, 1H), 7.76 (d, J ) 8.1 Hz, 1H), 7.87 (d, J )
8.1 Hz, 1H), 8.66 (d, J ) 8.1 Hz, 1H); 13C NMR (CDCl3) δ 29.04
(d, J ) 10.3 Hz), 29.19 (d, J ) 10.3 Hz), 45.35, 45.77 (d, J )
[R]20 +123 (c 1.0, CHCl3) for a mixture of (R,R)-7b of >99%
D
ee and meso-8b in a ratio of 88:12. (lit.10b [R]23D +120.1 (c 1.29,
CHCl3) for (R,R)-7b). meso-Fe[η5-C5H4CH(NMe2)(2-MeC6H4)]2
(8b): 1H NMR (CDCl3) δ 1.93 (s, 12H), 2.52 (s, 6H), 3.37 (s,
2H), 3.39 (s, 2H), 3.47 (s, 2H), 3.81 (s, 2H), 3.97 (s, 2H), 7.20-
7.15 (m, 4H), 7.28 (t, J ) 7.5 Hz, 2H), 7.60 (d, J ) 7.5 Hz,

Asymmetric Synthesis of Metallocenes
J . Org. Chem., Vol. 67, No. 10, 2002 3359
2H); 13C NMR (CDCl3) δ 20.66, 44.52, 66.07, 67.03, 67.11,
69.76, 71.32, 91.15, 125.96, 126.47, 127.42, 130.16, 135.10,
142.80. (R,R)-F e[η5-C5H 4CH (NMe2)P h ]2 (7a ): 1H NMR
(CDCl3) δ 1.97 (s, 12H), 3.48 (s, 4H), 3.56 (s, 2H), 3.58 (s, 2H),
3.87 (s, 2H), 7.41-7.26 (m, 10H); 13C NMR (CDCl3) δ 44.38,
67.52, 67.58, 69.95, 71.22, 72.23, 90.26, 126.85, 127.83, 128.23,
for a mixture of (R,R)-7d and meso-8d in a ratio of 92:8. m eso-
F e[η5-C5H4CH(NMe2)(1-n a p h th yl)]2 (8d ): 1H NMR (CDCl3)
δ 1.91 (s, 12H), 3.03 (s, 2H), 3.13 (s, 2H), 3.24 (s, 2H), 3.67 (s,
2H), 4.09 (s, 2H), 7.49 (t, J ) 8.0 Hz, 2H), 7.52 (t, J ) 8.0 Hz,
2H), 7.67-7.56 (m, 4H), 7.85 (d, J ) 8.0 Hz, 2H), 7.92 (d, J )
8.0 Hz, 2H), 8.49 (br, 2H); 13C NMR (CDCl3) δ 44.77, 66.92,
66.92, 67.41, 69.05, 71.58, 90.77, 124.38, 125.23, 125.36,
125.39, 127.23, 128.84, 131.86, 133.81, 140.26.
143.24; [R]20 +84 (c 1.0, CHCl3) for a mixture of isomers 7a
D
of 78% ee and meso-8a in a ratio of 63:37 (lit.10c [R]20 +103 (c
D
1.0, CHCl3) for a mixture of isomers 7a of 99% ee and meso-
8a in a ratio of 91:9). m eso-F e[η5-C5H4CH(NMe2)P h ]2 (8a ):
1H NMR (CDCl3) δ 1.94 (s, 12H), 3.43 (s, 4H), 3.55 (s, 2H),
3.58 (s, 2H), 3.89 (s, 2H), 7.41-7.26 (m, 10H); 13C NMR (CDCl3)
δ 44.27, 67.08, 67.70, 69.14, 71.67, 71.97, 126.89, 127.87,
128.35, 143.43. (R,R)-F e[η5-C5H4CH(NMe2)(2-MeOC6H4)]2
(7c): 1H NMR (CDCl3) δ 1.98 (s, 12H), 3.44 (s, 2H), 3.44 (s,
2H), 3.52 (s, 2H), 3.93 (s, 6H), 4.07 (s, 2H), 4.39 (s, 2H), 6.92
(d, J ) 7.7 Hz, 2H), 7.01 (t, J ) 7.7 Hz, 2H), 7.27-7.25 (m,
2H), 7.38 (t, J ) 7.7 Hz, 2H); 13C NMR (CDCl3) δ 44.11, 55.28,
61.22, 67.58, 67.89, 69.93, 71.58, 89.62, 110.12, 120.47, 127.53,
128.77, 131.33, 156.48. Anal. Calcd for C30H36N2O2Fe: C,
70.31; H, 7.08. Found: C, 70.21; H, 7.13 (a mixture of isomers
Or th o-Lith ia tion of F er r ocen e (R,R)-7b Givin g Dibr o-
m id e (R,R,SFc,SFc)-9b. To a mixture of 7b and 8b (100 mg,
0.20 mmol, 7b/8b ) 88/12) in dry ether (1.7 mL) was added
n-butyllithium (1.54 M, 0.64 mL, 1.0 mmol) at 0 °C. The
reaction mixture was stirred at room temperature for 6 h, and
1,2-dibromotetrafluoroethane (0.31 g, 1.2 mmol) was added at
0 °C. The reaction mixture was stirred at 40 °C for 1 h, and
then water (5 mL) was added. The reaction mixture was
extracted with ether. The combined extracts were washed with
aqueous sodium hydrogen carbonate solution and dried over
anhydrous magnesium sulfate. The solvent was evaporated,
and the residue was chromatographed on silica gel (5/4/0.1
hexane/diethyl ether/triethylamine) gave 76 mg (60% yield)
of (R,R,SFc,SFc)-Fe[η5-2-BrC5H3CH(NMe2)(2-MeC6H4)]2 (9b ).
(R,R,SFc,SFc)-F e[η5-2-Br C5H3CH(NMe2)(2-MeC6H4)]2 (9b):
1H NMR (CDCl3) δ 1.94 (s, 12H), 2.63 (s, 6H), 3.17 (s, 2H),
3.57 (s, 2H), 3.64 (s, 2H), 4.11 (s, 2H), 7.21-7.18 (m, 4H), 7.36-
7.33 (m, 2H), 7.49 (d, J ) 7.7 Hz, 2H); 13C NMR (CDCl3) δ
21.00, 44.22, 62.78, 67.15, 70.51, 74.15, 82.71, 90.71, 126.35,
127.10, 127.40, 130.16, 135.13, 142.91. Anal. Calcd for C30H34N2-
Br2Fe: C, 56.45; H, 5.37. Found: C, 56.71; H, 5.42. [R]20D +196
(c 1.0, CHCl3) for (R)-9b.
7c and 8c). [R]20 -45 (c 0.93, CHCl3) for a mixture of (R,R)-
D
7c of 99% ee and meso-8c in a ratio of 90:10. m eso-F e[η5-
C5H4CH(NMe2)(2-MeOC6H4)]2 (8c): 1H NMR (CDCl3) δ 1.96
(s, 12H), 3.44 (s, 2H), 3.47 (s, 2H), 3.49 (s, 2H), 3.93 (s, 6H),
4.07 (s, 2H), 4.29 (s, 2H), 6.94 (d, J ) 7.5 Hz, 2H), 7.05 (t, J )
7.5 Hz, 2H), 7.28-7.25 (m, 2H), 7.56 (d, J ) 7.5 Hz, 2H); 13C
NMR (CDCl3) δ 44.11, 55.32, 61.22, 67.47, 67.58, 69.54, 72.04,
89.90, 110.21, 120.27, 127.53, 128.64, 131.69, 156.71. (R,R)-
F e[η5-C5H4CH(NMe2)(1-n a p h th yl)]2 (7d ): 1H NMR (CDCl3)
δ 1.94 (s, 12H), 3.09 (s, 2H), 3.12 (s, 2H), 3.38 (s, 2H), 3.54 (s,
2H), 4.31 (s, 2H), 7.48 (t, J ) 8.0 Hz, 2H), 7.51 (t, J ) 8.0 Hz,
2H), 7.60-7.58 (m, 4H), 7.78 (d, J ) 8.0 Hz, 2H), 7.89 (d, J )
8.0 Hz, 2H), 8.57 (br, 2H); 13C NMR (CDCl3) δ 44.77, 66.99,
66.99, 67.41, 69.40, 71.42, 90.77, 124.41, 125.23, 125.36,
125.39, 127.23, 128.99, 131.81, 133.81, 140.01. Anal. Calcd for
Ack n ow led gm en t. This work was supported by
“Research for the Future” Program, the J apan Society
for the Promotion of Science, and a Grant-in-Aid for
Scientific Research, the Ministry of Education, J apan.
We thank Mr. Ryo Shintani for preliminary experiments.
C
36H36N2Fe: C, 78.26; H, 6.57. Found: C, 78.06; H, 6.56 (a
mixture of 7d and 8d ). [R]20 -59 (c 0.91, CHCl3) for (R)-7d
J O0111199
D