Preparation of chiral homoannularly bridged N,P-ferrocenyl ligands by intramolecular coupling of 1,5-dilithioferrocenes and their application in asymmetric allylic substitution reactions

Article abstract of DOI:10.1002/ejoc.200700470

Homoannularly bridged ferrocene 6b was prepared by intramolecular coupling of 1,5-dilithioferrocene 5b mediated by Fe(acac)₃. Dilithioferrocene 5b was prepared by lithium-halogen exchange of the corresponding diiodide, which was prepared by 1,5

Full text of DOI:10.1002/ejoc.200700470

FULL PAPER
DOI: 10.1002/ejoc.200700470
Preparation of Chiral Homoannularly Bridged N,P-Ferrocenyl Ligands by
Intramolecular Coupling of 1,5-Dilithioferrocenes and Their Application in
Asymmetric Allylic Substitution Reactions
Shin-ichi Fukuzawa,*[a] Masahisa Yamamoto,[a] Mitsuteru Hosaka,[a] and Satoshi Kikuchi[a]
Dedicated to the memory of Professor Yoshihiko Itoh
Keywords: Asymmetric catalysis / Asymmetric synthesis / N,P ligands / Chirality / Allylation / Annulation
Homoannularly bridged ferrocene 6b was prepared by intra-
molecular coupling of 1,5-dilithioferrocene 5b mediated by
Fe(acac)3. Dilithioferrocene 5b was prepared by lithium–
halogen exchange of the corresponding diiodide, which was
prepared by 1,5-dilithiation of the o-TMS-blocked ferrocene
and followed by trapping with iodine and removal of the
TMS group. Alternatively, 5b could be readily prepared by
trapped with Ph2PCl to produce corresponding aminophos-
phane 7d. Aminophosphane 13, which has the phosphanyl
group on the cyclopentadienyl ring, was prepared by intra-
molecular coupling of 1,5-dilithiated PhPPFA 11 mediated by
Fe(acac)3. New N,P ligands 7d and 13 were used in the palla-
dium-catalyzed allylic alkylation and amination of 1,3-di-
phenyl-2-propenyl acetate (14), and ligand 7d was found to
give good yields with enantioselectivities as high as 96% ee.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
the reaction of o-bromophenylferrocene
8 with nBuLi
(Ͼ2 equiv.). The benzene ring of 6b underwent ortho lithi-
ation with tBuLi, and the resulting lithiated species was
Introduction
Chiral ferrocenes are a group of compounds that have
central, planar, or C2 chirality, and many of these com-
pounds have a combination of these chiralities.[1] It is easy
to introduce a chiral group onto ferrocene and stereospecif-
ically carry out transformations of the functional group.
The unique structure of ferrocenes allows one to design a
variety of chiral ferrocenylphosphane ligands, which are
useful tools for metal-catalyzed asymmetric reactions.[2] Al-
though some useful chiral ferrocenyl phosphane ligands
such as taniaphos[3] and josiphos[4] have already been re-
ported, it is still of interest and a challenge to create new
ferrocenyl phosphane ligands that produce more effective
metal complex catalysts and/or to cover asymmetric reac-
tions in which conventional ligands do not effectively work.
Weissensteiner et al. prepared homoannularly bridged
chiral ferrocenes and studied their coordination chemis-
try.[5] These species possess lower conformational flexibility,
and they can occasionally work more efficiently than flexi-
ble ferrocenes as ligands in certain metal-catalyzed asym-
metric reactions. For example, PTFA {[(diphenylphos-
phanyl)tetramethyleneferrocenyl]dimethylamine, 1} gave
higher enantioselectivity (79% ee) than PPFA ({[(diphenyl-
phopsphanyl)ferrocenyl]ethyl}dimethylamine, 2; 63% ee) in
the palladium-catalyzed Grignard cross-coupling reaction
(Figure 1).[6]
Figure 1. The PTFA and PPFA ligands.
We previously reported that o-TMS-blocked ferrocene 3
underwent 1,5-dilithiation upon treatment with more than
one equivalent of nBuLi, and intramolecular coupling of
resulting 1,5-dilithioferrocene 5a occurred in the presence
of Fe(acac)3 to give homoannularly bridged ferrocene 6a
(Scheme 1).[7] We were interested in the unique structure of
6a and designed a new ferrocenyl phosphane ligand based
on its structure. Using the same intramolecular coupling
methodology, we succeeded in the preparation of new chiral
homoannularly bridged N,P-ferrocenyl ligands.[8] Palladium
complexes containing these ligands catalyzed allylic substi-
tutions with high enantioselectivities.[9]
[a] Department of Applied Chemistry, Institute of Science and
Engineering, Chuo University,
1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan
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Chiral Homoannularly Bridged N,P-Ferrocenyl Ligands
Scheme 1. Reagents and conditions: (a) tBuLi (2.4 equiv.) in diethyl
ether, 0 °C, 2 h, then I2 (2.5 equiv.); (b) tBuOK (1.1 equiv.) in
DMSO, room temp., 15 h; (c) nBuLi (2.5 equiv.) in diethyl ether,
0 °C, 2 h; (d) Fe(acac)3 (3.0 equiv.), 0 °C 10 min, then room temp.,
22 h.
Figure 2. X-ray structure of 7d. Selected bond lengths [Å]: C3–C4
1.511, C3–C14 1.537, C4–C8 1.428, C8–C9 1.473, C9–C14 1.411,
C13–C14 1.388, N1–C3 1.524, P1–C13 1.842. Selected bond angles
[°]: C3–C4–C8 110.3, C4–C3–C14 101.8, C8–C9–C14 107.8, C3–
C14–C9 111.0, C9–C14–C13 121.7, C3–C14–C13 127.0, P1–C13–
C14 116.14, N1–C3–C4 111.7, N1–C3–C14 111.5.
Results and Discussion
We first carried out ortho lithiation of 6b, which was
readily prepared by intramolecular coupling of TMS-free
ferrocenyl 1,5-diiodide 4b.[7] Upon treatment of 6b with
tBuLi (1 equiv.) followed by trapping with TMSCl, the
TMS group was exclusively introduced at the ortho position
of the benzene ring to give 7a. Contrary to our expectation,
the ortho position of the cyclopentadienyl moiety was not
silylated and the production of 6a was not observed. The
structure of 7a was determined by spectroscopic analysis;
the loss of the signal of one proton from the benzene ring
the (R,Sp) stereochemistry] could be prepared by trapping
with Ph2PCl,[3a] the intramolecular coupling of 9 should be
expected to give (R,Rp)-10. However, the stereochemistry
of the actual taniaphos product was not (R,Rp) but (R,Sp),
which was confirmed by X-ray crystallographic analysis,
that is, the stereochemistry of the product was identical to
that of 6b obtained by the annulation of 5b. This result was
confusing because the planar chirality of taniaphos is sup-
posed to be (Sp), which could be derived from (Rp)-lithio-
ferrocene 9 as was reported. One explanation could be that
isomerization of the 1,5-dilithioferrocene might occur dur-
ing the intramolecular coupling. This possibility, however,
was refuted by examination of the structure of original tania-
phos-Rh (CCDC-134965), which was carefully prepared by
Knochel et al.[3a] The correct stereochemistry of tania-
phos was found to be (R,Rp) as shown in Scheme 3; the
long convention of illustrating it as the (R,Sp) form is incor-
rect.[10] Therefore, ortho lithiation of 8 proceeded with (Sp)
stereochemistry to give 5b, from which intramolecular
coupling yielded (R,Sp)-6b. This process could provide a
more convenient route to 6b than that starting from o-
TMS-blocked ferrocene 3 (method B in the Experimental
Section).
1
in the H NMR spectra and the downfield shift of one of
the benzene carbon signals in the 13C NMR spectra indi-
cated that the replacement occurred at the benzene ring
(Scheme 2). Similarly, bromine and iodine atoms could be
introduced at the ortho position of the benzene ring to ob-
tain corresponding halides 7b,c. Thus, the preparation of
chiral aminophosphane 7d was accomplished by direct
ortho lithiation of 6b or lithiation of 7b,c and subsequent
trapping with diphenylphosphanyl chloride; compound 7d
was obtained in 63% yield. The structure of 7d was con-
firmed by X-ray crystallographic analysis (Figure 2).
We next outlined a synthesis for the preparation of ami-
nophosphane 13, which has the phosphanyl group in the
cyclopentadienyl ring ortho to the amino group. We first
unsuccessfully attempted a classical ipso substitution to ex-
change the silyl group for a halogen atom[11] en route to
the phosphane moiety. Our next synthetic route involved
intramolecular coupling of 1,5-dilithio-PhPPFA 11[12] in an
analogous manner to the successive 1,5-dilithiation and in-
tramolecular coupling of 3 but with a phosphane moiety in
Scheme 2. Reagents and conditions: (a) tBuLi (1.3 equiv.) in diethyl
ether, 0 °C, 2 h, then E+ (1.0 equiv.).
We tried to prepare the diastereomer of 6b Ϫ (R,Rp)-10 place of the TMS group. PhPPFA 11 could be 1,5-dilithi-
Ϫ by successive 1,5-dilithiation of (R)-o-bromophenylferro- ated upon treatment with tBuLi (Ͼ2 equiv.) and sub-
cene 8 and annulation of (R,Rp)-1,5-dilithioferrrocene 9, as sequently trapped with BrCF2CF2Br to give corresponding
shown in Scheme 3. Because taniaphos [thought to possess 1,5-dibromide 12 in 78% yield. Compound 12 was then
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S.-i. Fukuzawa, M. Yamamoto, M. Hosaka, S. Kikuchi
FULL PAPER
Scheme 3. Reagents and conditions: (a) tBuLi (3 equiv.) in diethyl ether, 0 °C, 2 h; (b) Fe(acac)3 (3 equiv.), 0 °C 10 min, then room temp.,
22 h; (c) Ph2PCl (2.5 equiv.), –78 °C, 1 h.
treated with tBuLi (2 equiv.) and subsequently with Fe- Table 1. Palladium-catalyzed asymmetric allylic alkylation with chi-
ral ferrocenyl N,P ligands.[a]
(acac)3, and the intramolecular coupling then proceeded to
ee [%][b] (Config.)
give aminophosphane 13 in 69% yield (Scheme 4).
Entry
Ligand
Yield [%]
1[c]
2[c]
3
4
5
1 (PTFA)
2 (PPFA)
7d
75
–
92
99
99
99
99
71 (S)
54 (R)
96 (R)
14 (S)
30 (S)
30 (S)
37 (S)
(R,Sp)-13
11 (PhPPFA)
12
6
7
taniaphos
[a] 14 (0.5 mmol), 15 (1.5 mmol), [Pd(η3-C3H5)Cl]2 (0.01 mmol,
2 mol-%), ligand (0.03 mmol, 6 mol-%), BSA (1.5 mmol), KOAc
(0.015 mmol); room temp., 13 h, in CH2Cl2 (3.0 mL). [b] Deter-
mined by HPLC (Chiralpack AD-H). [c] See ref.[5e]
Because 7d was revealed to be the most successful N,P-
ferrocenyl ligand examined here for asymmetric allylic alky-
lations, it was then further used for the asymmetric allylic
amination of 14 with benzylamine 17. The results of the
reaction under several conditions are summarized in
Table 2. We first carried out the reaction using a 2:1 ratio
of 17/14 and palladium/7d complex (2 mol-%) in THF at
room temperature, but amination product 18 was hardly
obtained (Table 2, Entry 1). However, the reaction pro-
ceeded smoothly in CH2Cl2 under similar conditions to give
(S)-configured product 18 in moderate yield with moderate
ee (Table 2, Entry 3). Finally, the use of a 4:1 ratio of 17/14
and the addition of tetrabutylammonium fluoride (TBAF)
Scheme 4. Reagents and conditions: (a) tBuLi (2.5 equiv.) in diethyl
ether, 0 °C, 2 h, then BrCF2CF2Br (3.0 equiv.); (b) tBuLi
(2.5 equiv.) in diethyl ether, 0 °C, 2 h, then Fe(acac)3 (3.0 equiv.),
0 °C 10 min, then room temp., 22 h.
Having achieved the preparation of homoannularly
bridged chiral aminophosphanes 7d and 13, we used them
in the benchmark palladium-catalyzed asymmetric allylic
alkylation reaction to demonstrate their ability as li-
gands.[13] Table 1 summarizes the results of the reaction of
(Ϯ)-(E)-1,3-diphenyl-2-propenyl acetate (14) with dimethyl
malonate (15). The reaction was carried out under condi-
tions that included a catalytic amount of [Pd(η3-C3H5)Cl]2
and either ligand 7d or 13 in the presence of N,O-bis(tri-
methylsilyl)acetamide (BSA) and a catalytic amount of po-
tassium acetate as the base. Detailed conditions are indi-
cated in Table 1.[14] The results of reactions involving other
related chiral N,P ligands, such as 1, 2, 11, 12, and tania-
phos, are also shown in Table 1 for comparison. These re-
sults show that 7d was the most effective as product 16 was
obtained in good yield with high enantiomeric excess (96%
ee; Table 1, Entry 3). N,P-ferrocenyl ligand 13 was less ef-
fective and gave a lower ee value relative to homoannularly
bridged N,P-ferrocenyl ligands 1 (PTFA) and 7d. However,
13 seems to give a somewhat higher selectivity than corre-
sponding flexible ligand 11 (Table 1, Entries 5, 7).
Table 2. Palladium-catalyzed asymmetric allylic amination in the
presence of 7d as ligand.[a]
Entry
Solvent
Additive
Yield [%] ee [%][b] (Config.)
1[c]
2[c,d]
3[c]
4
THF
THF
CH2Cl2
CH2Cl2
CH2Cl2
TBAF
TBAF
–
0
–
87
60
67
94
67 (S)
76 (S)
84 (S)
90 (S)
–
5
TBAF
[a] 14 (0.5 mmol), 17 (2.0 mmol), [Pd(η3-C3H5)Cl]2 (0.01 mmol.
2 mol-%), ligand (0.03 mmol, 6 mol-%), TBAF (1.0 mmol); room
temp., 18–24 h. [b] Determined by HPLC (Chiralpack AD-H). [c]
14 (2.0 mmol). [d] Reflux for 24 h.
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Chiral Homoannularly Bridged N,P-Ferrocenyl Ligands
mophenylmethyl]ferrocene (8; 1.9 g, 4.8 mmol) and dry diethyl
ether (30 mL) under a slight pressure of nitrogen. The flask was
cooled in a dry-ice bath, and a solution of tBuLi (1.58  in hexane,
9.5 mL, 15.0 mmol) was then added by syringe through the septum
whilst stirring. The mixture was warmed to room temp. and stirred
for 2 h. A solution of Fe(acac)3 (5.1 g, 14 mmol) in dry benzene
(30 mL) was then injected into the solution at 0 °C. The mixture
was stirred at 0 °C for 10 min, the ice bath was then removed, and
the mixture was warmed to room temp. and stirred for an ad-
ditional 22 h. The reaction was quenched with a 10% aqueous solu-
tion of NaOH, and the precipitate was removed by filtration
through a Celite pad. The filtrate was extracted with CH2Cl2
(3ϫ30 mL). The combined extracts were washed (brine), dried
(K2CO3), and filtered, and the solvent was removed under reduced
pressure. The crude dark orange solid was purified by column
chromatography on silica gel (hexane/ethyl acetate/triethylamine,
20:4:1) to give pure (R,Sp)-6b. Yield: 1.4 g, 4.4 mmol, 92%.
improved the results to 90% ee and 94% yield (Table 2, En-
try 5; Scheme 5). The addition of TBAF was essential to
obtain high enantioselectivity.[11b]
Scheme 5.
Typical Experimental Procedure for the Lithiation of 6b Followed by
Trapping with Electrophiles (Ph2PCl, TMSCl, BrCF2CF2Br, I2)
Conclusion
7d: To a 50-mL Schlenk tube containing a magnetic stirring bar
was added (R,Sp)-6b (1.0 g, 3.2 mmol) and dry diethyl ether
(20 mL) under a slight pressure of nitrogen. The tube was cooled
in an ice bath, and a solution of tBuLi (1.6  in hexane, 2.6 mL,
4.2 mmol) was added by syringe through the septum whilst stirring.
After 2 h, Ph2PCl (0.61 mL, 3.3 mmol) was added to the mixture;
the ice bath was then removed, and the mixture was warmed to
room temp. and stirred for an additional 20 h. The reaction was
quenched with saturated aqueous NaHCO3, and the solution was
then extracted with diethyl ether (3ϫ30 mL). The combined ex-
tracts were washed (brine), dried (K2CO3), and filtered, and the
solvent was removed under reduced pressure. The brown residue
was purified by column chromatography on silica gel (hexane/ethyl
acetate/triethylamine, 20:2:1) to give pure 7d as a yellow solid.
Yield: 1.0 g, 2.0 mmol, 63%. M.p. 39 °C. [α]2D5 = –864 (c = 0.14,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 1.78 (s, 6 H, NMe2),
3.87 (s, 5 H, Cp), 4.20 (t, J = 2.2 Hz, 1 H, Cp-H), 4.44 (d, J =
2.2 Hz, 1 H, Cp-H), 4.46 (d, J = 2.2 Hz, 1 H, Cp-H), 4.79 (s, 1 H,
CHN), 6.70 (dd, J = 4.6, 7.6 Hz, 1 H), 7.1 (t, J = 7.6 Hz, 1 H),
7.2–7.5 (m, 11 H, aromatic signals) ppm. 13C NMR (125 MHz,
CDCl3): δ = 39.7 (NMe2), 59.1 (CNMe2), 64.9, 68.1, 69.9, 70.2,
90.3, 91.3, 119.4, 127.8–128.7 (several aromatic signals), 129.5,
133.9, 134.1, 134.2, 134.4, 135.7 (d, JP,C = 19.1 Hz), 137.2 (d, JP,C
= 10.8 Hz), 138.0 (d, JP,C = 11.4 Hz), 141.2 (d, JP,C = 6.30 Hz),
151.7 (d, JP,C = 20.7 Hz) ppm. 31P NMR (202 MHz, CDCl3): δ =
–13.7 (JP,H = 11.0 Hz) ppm. HRMS: calcd. for C31H28FeNP [M +
H]+ 502.1387; found 502.1356. Crystals suitable for X-ray analysis
were obtained by recrystallization from CHCl3/hexane.
In conclusion, we prepared homoannularly bridged N,P-
ferrocenyl ligands by intramolecular coupling of 1,5-di-
lithioferrocene. In particular, 7d was the most successful li-
gand in the palladium-catalyzed allylic substitution of 1,3-
diphenyl-2-propenyl acetate (14), and produced products
with up to 96% ee. Further studies of the application of 7d
to metal-catalyzed asymmetric reactions are in progress.
Experimental Section
(Cyclopentadienyl){(R,Sp)-η5-8-(dimethylamino)dihydrocyclopenta-
[a]indenyl}iron(II) (6b)
Method A: To a 200-mL three-neck round-bottom flask containing
a magnetic stirring bar was added (Rp)-1-iodo-2-[(R)-1-(dimeth-
ylamino)-o-iodophenylmethyl]ferrocene[7] (4b; 5.71 g, 10.0 mmol)
and dry diethyl ether (70 mL) under a slight pressure of nitrogen.
The flask was cooled in an ice bath and a solution of nBuLi (1.6 
in hexane, 15.8 mL, 25.0 mmol) was then added by syringe through
the septum whilst stirring. After 2 h, a solution of Fe(acac)3 (10.6 g,
30.0 mmol) in dry benzene (45 mL) was injected into the solution,
and the mixture was stirred at 0 °C for 10 min. The ice bath was
then removed, and the mixture was warmed to room temp. and
stirred for an additional 22 h. The reaction was quenched with a
10% aqueous solution of NaOH, and the precipitate was removed
by filtration through a Celite pad. The filtrate was extracted with
CH2Cl2 (3ϫ30 mL). The combined extracts were washed (brine),
dried (K2CO3), and filtered, and the solvent was removed under
reduced pressure. The crude dark orange solid was purified by col-
umn chromatography on silica gel (hexane/ethyl acetate/triethyl-
amine, 20:4:1) to give pure (R,Sp)-6b as orange crystals. Yield:
3.0 g, 9.5 mmol, 95%. M.p. 92 °C. [α]2D5 = –774 (c = 0.16, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 2.13 (s, 6 H, NMe2), 3.87 (s, 5
H, Cp), 4.25 (t, J = 2.3 Hz, 1 H, Cp-H), 4.51 (d, J = 1.9 Hz, 1 H,
Cp-H), 4.56 (d, J = 2.2 Hz, 1 H, Cp-H), 4.99 (s, 1 H, CHN), 7.14
(d, J = 7.3 Hz, 1 H), 7.22 (t, J = 7.3 Hz, 1 H), 7.31 (d, J = 7.3 Hz,
1 H), 7.42 (d, J = 7.3 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 40.8 (NMe2), 59.2 (CNMe2), 65.1, 68.5, 70.1, 70.3, 90.6, 91.4,
119.6, 125.0 125.4, 127.9, 141.6, 147.5 ppm. HRMS: calcd. for
C19H19FeN [M + H]+ 318.0914; found 318.0939.
7a: Orange solid. Yield: 0.75 g, 60%. M.p. 84 °C. [α]2D5 = –972 (c =
0.65, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 0.35 (s, 9 H,
SiMe3), 2.00 (br. s, 6 H, NMe2), 3.86 (s, 5 H, Cp), 422 (t, J =
2.3 Hz, 1 H, Cp-H), 4.48 (d, J = 2.3 Hz, 1 H, Cp-H), 4.54 (d, J =
2.3 Hz, 1 H, Cp-H), 4.97 (s, 1 H, CHN), 7.15–7.35 (m, 3 H, aro-
matic signals) ppm. 13C NMR (125 MHz, CDCl3): δ = –0.31
(SiMe3), 40.1 (NMe2), 58.9 (CNMe2), 64.9, 68.5, 69.6, 70.2, 90.7,
91.0, 121.0, 127.0, 131.3, 137.3, 140.3, 153.9 ppm. C22H27FeNSi
(389.39): calcd. C 67.86, H 6.99, N 3.60; found C 67.64, H 7.13, N
3.44.
7b: Orange solid. Yield: 1.0 g, 79%. M.p. 46 °C. [α]2D5 = –1303 (c =
0.20, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 2.09 (s, 6 H,
NMe2), 3.89 (s, 5 H, Cp), 4.29 (t, J = 2.2 Hz, 1 H, Cp-H), 4.54 (d,
J = 2.2 Hz, 1 H, Cp-H), 4.56 (d, J = 2.2 Hz, 1 H, Cp-H), 4.95 (s,
1 H, CHN), 7.09 (t, J = 7.7 Hz, 1 H), 7.23 (d, J = 7.7 Hz, 1 H),
Method B: To a 200-mL three-neck round-bottom flask containing
a magnetic stirring bar was added [(R)-1-(dimethylamino)-o-bro-
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S.-i. Fukuzawa, M. Yamamoto, M. Hosaka, S. Kikuchi
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7.28 (d, J = 7.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = (d, JP,C = 14.4 Hz), 93.5, 99.5 (d, JP,C = 28.8 Hz), 119.2, 125.0–
40.4 (NMe2), 59.7 (CNMe2), 65.2, 69.2, 70.3, 70.4, 89.6, 90.1, 140.8 (several aromatic signals), 138.2 (d, JP,C = 8.4 Hz), 140.1 (d,
118.2, 120.5, 129.1, 129.6, 144.3, 146.1 ppm. HRMS: calcd. for JP,C = 8.4 Hz), 147.8 ppm. 31P NMR (202 MHz, CDCl3): δ = –21.1
C19H18BrFeN [M + H]+ 396.0019; found 396.0110.
(JP,H = 9.2 Hz) ppm. HRMS: calcd. for C31H28FeNP [M + H]+
502.1356; found 502.1418.
7c: Orange oil. Yield: 1.1 g, 78%. [α]2D5 = –1198 (c = 0.30, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 2.05 (s, 6 H, NMe2), 3.87 (s, 5
H, Cp-H), 4.26 (t, J = 2.2 Hz, 1 H, Cp-H), 4.51 (d, J = 2.2 Hz, 1
H, Cp-H), 4.54 (d, J = 2.2 Hz, 1 H, Cp-H), 4.75 (s, 1 H, CHN),
6.91 (t, J = 7.7 Hz, 1 H), 7.23 (d, J = 7.7 Hz, 1 H), 7.52 (d, J =
7.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 40.2 (NMe2),
59.7 (CNMe2), 65.1, 70.3, 70.4, 71.1, 89.7, 90.2, 93.7, 118.9, 129.6,
135.3, 143.7, 149.7 ppm. HRMS: calcd. for C19H18FeIN [M + H]+
443.9880; found 443.9864.
Palladium-Catalyzed Allylic Alkylation of (؎)-1,3-Diphenyl-2-pro-
penyl Acetate (14): To a Schlenk tube containing a stirring bar was
added [Pd(η3-C3H5)Cl]2 (3.8 mg, 0.01 mmol, 2 mol-%) and ligand
7d (15 mg, 0.03 mmol) dissolved in CH2Cl2 (3.0 mL). The mixture
was stirred under an atmosphere of argon at room temp. for
30 min. Compound 14 (126 mg, 0.5 mmol), dimethyl malonate (15;
170 mL, 1.5 mmol), N,O-bis(trimethylsilyl)acetamide (370 mL,
1.5 mmol), and potassium acetate (1.5 mg, 0.015 mmol) were suc-
cessively added to this solution. The mixture was stirred at room
temp. and monitored by TLC. After completion (13 h), the mixture
was diluted with CH2Cl2 (20 mL), washed with saturated aqueous
NH4Cl, dried (MgSO4), and filtered. The solvent was removed un-
der reduced pressure, and the brown residue was subjected to
PTLC (hexane/ethyl acetate, 40:3) to give pure 16. Yield: 150 mg,
1,5-Dibromo PhPPFA (12): To a 300-mL three-neck round-bottom
flask containing a magnetic stirring bar was added (R,Sp)-11
(PhPPFA; 1.7 g, 3.4 mmol) and dry diethyl ether (30 mL) under a
slight pressure of nitrogen. The flask was cooled in an ice bath,
and a solution of tBuLi (1.6  in hexane, 5.4 mL, 8.5 mmol) was
then added by syringe through the septum whilst stirring. After
2 h, a solution of BrCF2CF2Br (1.2 mL, 10 mmol) in THF (40 mL)
was injected into the mixture; the ice bath was then removed, and
the mixture was warmed to room temp. and stirred for an ad-
ditional 16 h. The reaction was quenched with saturated aqueous
NH4Cl, and extracted with CH2Cl2 (3ϫ30 mL). The combined ex-
tracts were washed (brine), dried (K2CO3), and filtered, and the
solvent was removed under reduced pressure. The orange residue
was purified by column chromatography on silica gel (hexane/ethyl
acetate/triethylamine, 20:4:1) to give pure 12 as an orange solid.
Yield: 1.75 g, 2.6 mmol, 78%. M.p. 177 °C. [α]2D5 = –266 (c = 0.20,
CHCl3). 1H NMR (500 MHz, CDCl3): δ = 2.04 (s, 6 H, NMe2),
3.68 (s, 5 H, Cp), 3.88 (d, J = 2.0 Hz, 1 H, CHN), 4.57 (d, J =
2.2 Hz, 1 H, Cp-H), 5.13 (d, J = 4.6 Hz, 1 H, Cp-H), 7.08–7.90 (m,
14 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 45.1 (NMe2), 68.4,
69.6 (d, JP,C = 3.6 Hz), 72.6, 73.2, 77.8 (d, JP,C = 19.2 Hz), 78.9,
1
0.46 mmol, 93%. H NMR (300 MHz, CDCl3): δ = 3.51 (s, 3 H,
CH3), 3.70 (s, 3 H, CH3), 3.96 (d, J = 10.9 Hz, 1 H, CHCO), 4.26
(dd, J = 8.7, 10.9 Hz, 1 H, CHPh), 6.33 (dd, J = 8.7, 15.7 Hz, 1
H, =CHCH), 6.46 (d, J = 15.7 Hz, 1 H, PhCH=), 7.2–7.3 (m, 10
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 49.0 (CHPh), 52.3
(CH3), 52.5 (CH3), 57.5 (CHCO), 126.3, 127.1, 127.5, 127.6, 127.7,
127.8, 128.1, 128.4, 128.5, 128.6, 129.0, 131.7, 136.7, 140.0, 167.5
(CO), 168.1 (CO) ppm. The ee of the product (96%) was deter-
mined by HPLC [Chiralpack AD-H, 25 cm; hexane/2-propanol,
90:10, 1.0 mL/min, tR(R) = 11.5 min, tR(S) = 16.1 min].
Palladium-Catalyzed Allylic Amination of 14: To a Schlenk tube
containing a stirring bar was added [Pd(η3-C3H5)Cl]2 (3.8 mg,
0.01 mmol, 2 mol-%) and ligand 7d (15 mg, 0.03 mmol) dissolved
in dry CH2Cl2 (2.0 mL), and the mixture was stirred under an at-
mosphere of argon at room temp. for 30 min. Compound 14
(126 mg, 0.5 mmol), benzylamine 17 (0.43 g, 4.0 mmol), and TBAF
(1  in THF, 1.0 mL, 1.0 mmol) were successively added to this
solution. The mixture was stirred at room temp. and monitored by
TLC. After completion (18 h), the mixture was diluted with diethyl
ether (20 mL), washed with saturated aqueous NH4Cl, dried
(MgSO4), and filtered. The solvent was removed under reduced
pressure. The brown residue was subjected to PTLC (hexane/ethyl
93.1 (d, JP,C = 20.0 Hz), 127.8 (d, JP,C = 6.0 Hz), 132.4 (d, JP,C
=
6.0 Hz), 139.0 (d, JP,C = 15.6 Hz), 139.2 (d, JP,C = 11.2 Hz), 125.6–
143.1 (several aromatic signals) ppm. 31P NMR (202 MHz,
CDCl3): δ = –23.7 (JP,H = 9.9 Hz) ppm. HRMS: calcd. for
C31H28Br2FeNP [M + H]+ 661.9722; found 661.9429.
(Cyclopentadienyl)({(R,Sp,Sp)-η5-{8-(dimethylamino)-1-(diphenyl-
phosphanyl)dihydrocyclopenta[a]indenyl})iron(II) (13): To a 300-mL
three-neck round-bottom flask containing a magnetic stirring bar
was added 12 (1.0 g, 1.5 mmol) and dry diethyl ether (25 mL) under
a slight pressure of nitrogen. The flask was cooled in an ice bath,
and a solution of tBuLi (1.58  in hexane, 2.4 mL, 3.8 mmol) was
then added by syringe through the septum whilst stirring. After
2 h, a solution of Fe(acac)3 (1.6 g, 4.5 mmol) in benzene (10 mL)
was added to the reaction solution; the ice bath was then removed,
and the mixture was warmed to room temp. and stirred for an
additional 22 h. The reaction was quenched with a 10% aqueous
solution of NaOH, and the precipitate was removed by filtration
through a Celite pad. The filtrate was extracted with CH2Cl2
(3ϫ30 mL). The combined extracts were washed (brine), dried
(K2CO3), and filtered, and the solvent was removed under reduced
pressure. The dark orange residue was purified by column
chromatography on silica gel (hexane/ethyl acetate/triethylamine,
20:4:1) to give pure 13 as an orange solid. Yield: 0.53 g, 1.06 mmol,
70%. M.p. 47 °C. [α]2D5 = –460 (c = 0.1, CHCl3). 1H NMR
1
acetate, 40:3) to give pure 18. Yield: 140 mg, 0.47 mmol, 94%. H
NMR (300 MHz, CDCl3): δ = 1.74 (br. s, 1 H), 3.74 (d, J =
13.3 Hz, 1 H, one of PhCH2N), 3.78 (d, J = 13.3 Hz, 1 H, one of
PhCH2N), 4.37 (d, J = 7.4 Hz, 1 H, CHNH), 6.30 (dd, J = 7.4,
15.9 Hz, 1 H, =CHCH), 6.56 (d, J = 15.9 Hz, 1 H, PhCH=), 7.2–
7.4 (m, 15 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 51.3
(CH2NH), 64.5 (CHNH), 126.4–129.0 (several aromatic signals),
130.3, 132.5, 136.8, 140.3, 142.8 ppm. The ee of the product (90%)
was determined by HPLC [Chiracel OJ-H, 25 cm; hexane/2-propa-
nol, 90–10, 0.6 mL/min, tR(S) = 18.1 min, tR(R) = 22.7 min].
Crystallographic Data: CCDC-641401 (for 7d) contains the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgments
(500 MHz, CDCl3): δ = 1.98 (s, 6 H, NMe2), 3.37 (s, 1 H, CHN), We wish to thank Professor Youichi Ishii and Dr. Yoshiaki Tanabe
3.67 (t, 5 H, Cp), 4.74 (s, 1 H), 5.08 (s, 1 H), 7.11–7.59 (m, 14 of the Department of Applied Chemistry, Chuo University, for the
H, aromatic signals) ppm. 13C NMR (125 MHz, CDCl3): δ = 40.6 X-ray diffraction analysis of the chiral ferrocene compounds. This
(NMe2), 62.1 (CNMe2), 68.7, 70.0 (d, JP,C = 19.2 Hz), 71.7, 72.3
study was financially supported by a Grant-in-Aid for Scientific
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5540–5545

Chiral Homoannularly Bridged N,P-Ferrocenyl Ligands
dia-taniaphos. The incorrect structure of taniaphos as it has
long been illustrated corresponds to dia-taniaphos. It is still not
known why the stereochemistry of o-lithiation of (R)-8 is (Sp),
whereas that of ortho lithiation of bromo-free (R)-(1-dimeth-
ylamino)phenylmethylferrocene is (Rp), even though both of
them have the same stereochemistry at the amino carbon. The
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[10] In our previous work (see ref.[7]) we reported that (R,Rp)-1,5-
diphosphane was prepared by the reaction of 1,5-dilithioferro-
cene 3b with Ph2PCl, and we stated that it was the diastereomer
of taniaphos. The present study revealed that the correct stereo-
chemistry of taniaphos is (R,Rp) as illustrated in Scheme 3, so
the 1,5-diphosphane we prepared is in fact taniaphos and not
[14] The reaction conditions were optimized by examining several
additives. The ee values for additives are as follows: LiOAc:
80% ee, NaOAc: 81% ee, KOAc: 96% ee, Cs2CO3: 82% ee, and
KOAc: in THF 90% ee.
Received: May 25, 2007
Published Online: September 21, 2007
Eur. J. Org. Chem. 2007, 5540–5545
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5545