Novel C2-symmetric 1,1′-disubstituted ferrocenyl aziridino alcohol ligands: Remarkable improvement of enantioselectivity in the catalytic asymmetric addition of diethylzinc to aldehydes

Article abstract of DOI:10.1055/s-2005-916038

A series of novel chiral C₂-symmetric 1,1′-disubstituted ferrocenyl aziridino alcohols have been readily synthesized and applied as catalysts to promote enantioselective addition of diethylzinc to aldehydes affording the corresponding 1-propano

Full text of DOI:10.1055/s-2005-916038

3620
PAPER
Novel C2-Symmetric 1,1¢-Disubstituted Ferrocenyl Aziridino Alcohol
Ligands: Remarkable Improvement of Enantioselectivity in the Catalytic
Asymmetric Addition of Diethylzinc to Aldehydes
Ferrocenyl
A
ziridino A
i
lcohol
n
s
Ligands -Can Wang,* Xue-Hui Hou, Cui-Lian Xu, Lan-Tao Liu, Gui-Lan Li, De-Kun Wang
Department of Chemistry, Zhengzhou University, Zhengzhou, Henan 450052, P. R. of China
Fax +86(371)67769024; E-mail: wangmincan@zzu.edu.cn
Received 26 May 2005; revised 28 June 2005
tion. Now we set out to extend this study and to explore
Abstract: A series of novel chiral C2-symmetric 1,1¢-disubstituted
ferrocenyl aziridino alcohols have been readily synthesized and ap-
plied as catalysts to promote enantioselective addition of diethyl-
zinc to aldehydes affording the corresponding 1-propanols in up to
the chemistry of C2-symmetric ferrocenyl aziridino alco-
hols. In this paper, we report the synthesis and use of a
novel series of C2-symmetric 1,1¢-disubstituted chiral fer-
99.5% enantiomeric excess with excellent yields. The effect of the rocenyl aziridino alcohols as catalysts for the enantiose-
ligand structure on the enantioselectivity was examined. The results
lective addition of diethylzinc to aldehydes.
showed that the C2-symmetric ferrocenyl b-amino alcohol ligands
could produce an excellent asymmetric environment for the asym-
metric addition of diethylzinc to aldehydes. The absolute configura-
tion of chiral C2-symmetric ferrocenyl aziridino alcohol ligand 8j
CH3
N
N
R
R
Fe
Fe
was confirmed by X-ray diffraction analysis.
HO
R
HO
R
Key words: aziridino alcohols, ferrocenyl, asymmetric addition,
diethylzinc, aldehydes
1
2
Figure 1
The design of economic and efficient chiral ligands for
highly enantioselective transformations has been one of
the major projects in asymmetric synthesis.1 The asym-
metric addition of organozincs to aldehydes remains the
focus of much research activity in asymmetric C–C bond
formation as evidenced by hundreds of research papers
and several comprehensive review articles.2 In addition,
the reaction of diethylzinc with aldehydes has also be-
come a classical test in the design of new ligands for cat-
alytic enantioselective synthesis.
We developed an improved procedure for the synthesis of
ferrocene-1,1¢-dicarboxaldehyde from 1,1¢-di(hy-
4
droxymethyl)ferrocene 3 based, in part, on conditions re-
ported by Osgerby and Pauson.8 Thus, the oxidation of
diol 3 was carried out in the presence of ‘active’ manga-
nese dioxide9 in chloroform at reflux for four hours. The
dialdehyde 4 was isolated in 69% yield after work-up
(Scheme 1).
CH2OH
CH2OH
CHO
MnO2
C2-Symmetric chiral ligands were shown to be efficient
for asymmetric induction and this has prompted chemists
to synthesize a range of chiral ligands with C2-symmetry.3
Among them, C2-symmetric ferrocenyl ligands have re-
ceived much attention in recent years.4 However, to the
best of our knowledge, there has been only one example
of a C2-symmetric 1,1¢-disubstituted chiral ferrocenyl
with b-amino alcohol ligands.5 Aziridino alcohols belong
to the three-membered ring heterocycle class of ligands
and they have attracted the interest of many chemists in
the transition metal-catalyzed asymmetric synthesis6 be-
cause of its rigid ring structure, that is considered to be the
determining factor in its effectiveness in asymmetric ca-
talysis. Recently, we reported the synthesis of chiral fer-
rocenyl aziridino alcohol ligands 1 and 2 and their
application to the enantioselective addition of diethylzinc
to aldehydes (Figure 1).7 Good to excellent enantioselec-
tivities were achieved in this asymmetric addition reac-
Fe
Fe
CHO
4: 69%
3
Scheme 1 Synthesis of ferrocene-1,1¢-dicarboxaldehyde 4
The ferrocenyl aziridino alcohols 8a–j were then prepared
in three steps as shown in Scheme 2. First, ferrocene-1,1¢-
dicarboxaldehyde 4 was reacted in methanol in the pres-
ence of triethylamine with methyl threonine ester hydro-
chloride giving the corresponding imines 5. Then,
reduction of 5, carried out on the crude reaction mixture,
with sodium borohydride in methanol provided com-
pound 6 in 69% overall yield after work-up. Next, 6 was
cyclized to aziridino ester 7 in 87% yield by reaction with
triphenyl phosphine in the presence of tetrachloromethane
in acetonitrile. Reduction with lithium aluminum hydride
led to the aziridino alcohol 8a in 66% chemical yield.
Treatment of 7 with an excess of Grignard reagent afford-
ed the ligands 8a–j in 55–88% yield.
SYNTHESIS 2005, No. 20, pp 3620–3626
x
x.
x
x
.
2
0
0
5
Advanced online publication: 12.10.2005
DOI: 10.1055/s-2005-916038; Art ID: F09705SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Ferrocenyl Aziridino Alcohol Ligands
3621
HO
HO
OH
CH3
CH3
CO2CH3
CH3
H
CO2CH3
NH2HCl
Et3N, MeOH
N
N
H3C
CO2CH3
CH3
NaBH4
HO
HO
Fe
Fe
4
H
N
N
CO2CH3
CO2CH3
5
6: 69%
CH3
CH3
N
R
N
N
PPh3, CCl4
Et3N, MeCN
CO2CH3
CH3
LiAlH4 or
RMgX
R
HO
Fe
Fe
CH3
R
N
CO2CH3
7: 87%
HO
8
R
8a: R = H (66%); 8b: R = Me (55%); 8c: R = Et (62%); 8d: R = n-Pr (64%);
8e: R = i-Pr (62%); 8f: R = n-Bu (58%); 8g: R = i-Bu (53%); 8h: R = n-C5H11 (73%);
8i: R = i-C5H11 (64%); 8j: R = Ph (88%)
Scheme 2 Synthesis of chiral ligands 8a–j
was confirmed by X-ray diffraction analysis10 (Figure 2).
The crystal structure of compound 8j reveals that the ni-
trogen atom on the aziridine ring is also a stereocenter,
possibly due to the strong interaction between the bulky
ferrocenyl group on the nitrogen atom of the aziridine ring
and the bulky diphenylhydroxymethyl group on the three-
membered ring, which leads to a tetrahedral structure with
a stable conformation. The stereocenter could also result
from the formation of an intramolecular hydrogen bond,
which further barricades nitrogen pyramidal inversion.
From the X-ray studies it was deduced that hydrogen
bonds are present in compound 8j. The N1–H1 and N2–
H2 distances in 8j are determined from the X-ray diffrac-
tion data and are shown to be 2.12 and 1.99 Å, respective-
ly. These distances between the aziridine nitrogen and the
hydroxyl hydrogen atom are indicative of the presence of
intramolecular hydrogen bonds in aziridine alcohol 8j,
which are close to the expected average value for a hydro-
gen bond present in a five-membered ring structure.
With these new ligands in hand, the addition reaction of
diethylzinc to benzaldehydes was carried to determine the
asymmetric induction achieved (Table 1).
As can be seen from Table 1, the addition of diethylzinc
to benzaldehyde led to 1-phenylpropanol in 65–90%
yields with 2.1–92.6% ee (Table 1, entries 1–10). The
enantioselectivity of the reaction is highly dependent on
the structure of the chiral catalyst. The ee increased as the
bulkiness of the R group increased (Table 1, entries 1–4).
The best asymmetric induction (92.6% ee) was observed
with ligand 8e, where R was a secondary alkyl substituent,
an isopropyl group. When the carbon chain length was in-
creased further the enantioselectivity was found to de-
crease (Table 1, compare entry 5 versus 6, 7, 8, and 9).
The presence of two phenyl groups in 8j resulted in the
lowest ee (2.1% ee). These results might reflect the differ-
ent steric effects on the enantioselectivity resulting from
the differently sized R groups. More interestingly, the
configuration of 1-phenylpropanol, with ligand 8c, was
Figure 2 Perspective view of compound 8j. Selected bond di-
stances (Å) and angles (°) are: O(1)–C(13), 1.420 (5); O(2)–C(29),
1.421 (5); O(1)–H(1), 0.78 (4); O(2)–H(2), 0.79(5); N(1)–H(1), 2.12
(4); N(2)–H(2), 1.995; N(1)–C(14), 1.462 (5); N(1)–C(15), 1.462 (5);
N(1)–C(17), 1.487 (5); N(2)–C(30), 1.468 (5); N(2)–C(31), 1.476 (5);
N(2)–C(28), 1.481 (5); (13)–C(14), 1.531 (5); C(14)–C(15), 1.484
(6); C(15)–C(16), 1.510 (6); C(29)–C(30), 1.534 (6); C(30)–C(31),
1.492 (6); C(31)–C(32), 1.503 (6); O(1)–H(1)–N(1), 130 (4); O(2)–
H(2)–N(2), 138 (5)
All new ferrocenyl ligands were air-stable and gave satis-
factory analytical and spectroscopic data. The absolute
configuration of chiral C2-symmetric ferrocenyl ligand 8j
Synthesis 2005, No. 20, 3620–3626 © Thieme Stuttgart · New York

3622
M.-C. Wang et al.
PAPER
Recently, the C2-symmetric ferrocene-based bis(amino al-
cohol)s such as 9 (Figure 3) with various substituents at
the nitrogen and oxygen carbons were reported by Pélins-
ki et al. for the catalytic asymmetric addition of diethyl-
zinc to benzaldehyde with 83% ee.5b They concluded that
the disubstituted ferrocenyl derivatives generally appear
to be unsuited as ligands in the addition of diethylzinc to
benzaldehyde. Comparison of our results with those of
Pélinski et al. demonstrates that the rigid structure (three-
membered heterocycle, see crystal structure) and fine-tun-
ing of the disubstituted ferrocenyl derivatives could lead
to substantial improvement in the enantioselectivity.
These results also show that the C2-symmetric ferrocenyl
b-amino alcohol ligands can produce an excellent asym-
metric environment for asymmetric alkylation of benzal-
dehyde.
Table 1 Addition of Diethylzinc to Benzaldehyde Catalyzed by
Ligands 8a
O
OH
Et2Zn, 5 mol% ligand
toluene, 0 °C, 48 h
Ph
H
Ph
Entry Ligand
Yield (%)b
ee (%)c
13.8
20.4
30.1
68.5
92.6
64.8
63.4
68.7
47.2
2.1
Configurationd
1
2
8a
8b
8c
8d
8e
8f
72
84
65
88
68
80
89
90
65
71
S
S
R
S
S
S
S
S
S
S
3
4
5
6
7
8g
8h
8i
CH3
8
OH
N
Ph
Ph
H
9
Fe
H
N
Ph
Ph
OH
10
8j
CH3
a Reagents: Et2Zn (2 equiv), aldehyde (1 equiv).
b Isolated yields.
9 83% ee
c Determined by HPLC using a chiral OD column.
Figure 3
d Absolute configuration assigned by comparison with the sign of op-
tical rotation of known compound and known elution order from a
Chiralcel OD column.
The ferrocenyl aziridino alcohol 8e was chosen as the best
chiral ligand for further investigation into the effects of
the catalytic amount and temperature on the asymmetric
induction, and the results are shown in Table 2. The best
result was obtained with 5 mol% of 8e at 0 °C (Table 2,
entry 3). When the reaction was carried out at room tem-
perature (20–25 °C) the selectivity decreased from 92.6%
to 87.2%.
found to be the opposite to that observed with all other
ligands, although the chirality of the ligand itself was the
same. A similar phenomenon was observed by Sibi11 and
Wang12 using b-amino alcohols as chiral ligands in the ad-
dition of diethylzinc to benzaldehyde.
Previously, we reported the synthesis of monosubstituted
ferrocenyl aziridino alcohol ligands 2 and their applica-
tion in the enantioselective addition of diethylzinc to alde-
hydes.7c The best asymmetric induction (only 69% ee)
was obtained for the catalytic asymmetric addition of di-
ethylzinc to benzaldehyde in the presence of ligand 2
(R = n-C4H9, 5 mol%). Comparison of the disubstituted
ligand 8e with C2-axial symmetry and the corresponding
monosubstituted ligands 2 (R = i-C3H7) with C1-axial
symmetry is noteworthy: the stereodifferentiating ability
of the 1,1¢-disubstituted ligand 8e (92.6% ee) is greater
than the corresponding monosubstituted ligands 2 (R =
i-C3H7, 52% ee), under the same conditions. This result
indicates that the introduction of C2-axial symmetry leads
to a dramatic improvement in the enantioselectivity in the
addition of diethylzinc to benzaldehyde. It is possibly due
to the homotopic nature of the remaining coordination
sites of the complexes formed by the ligand results in re-
ducing the number of competing diastereomeric path-
ways. These results suggest that the symmetry of ligands
8e with C2-axial symmetry are comparable with the corre-
sponding monosubstituted ligands 2 (R = i-C3H7) with C1-
axial symmetry.
Table 2 Asymmetric Addition of Diethylzinc to Benzaldehyde
Using Ligand 8ea
Entry Temperature 8e
Yield
(%)b
ee
Configurationd
(°C)
mol%
(%)c
1
2
3
4
5
6
0
0.5
2
60
69
91
85
83
88
21.3
70.0
92.6
92.3
91.9
87.2
S
S
S
S
S
S
0
0
5
0
8
0
10
r.t.
5
a Reagents: Et2Zn (2 equiv), aldehyde (1 equiv).
b Isolated yields.
c Determined by HPLC using a chiral OD column.
d Absolute configuration assigned by comparison with the sign of
optical rotation of a known compound and known elution order from
a Chiralcel OD column.
Synthesis 2005, No. 20, 3620–3626 © Thieme Stuttgart · New York

PAPER
Ferrocenyl Aziridino Alcohol Ligands
3623
Methyl threonine ester hydrochloride was prepared according to the
published procedure.13 All other reagents were commercially avail-
able and used as received. THF and Et2O were distilled from sodium
benzophenone ketyl. Petroleum ether with a bp range 60–90 °C was
used. Melting points were determined using YRT-3 melting point
apparatus, and were uncorrected. Optical rotations were measured
with Perkin Elmer, model 341 Polarimeter at 20 °C in CHCl3.
The chiral ligand 8e was applied to the asymmetric addi-
tion of diethylzinc to a series of aldehydes under the opti-
mized conditions (Table 3). As can be seen from Table 3,
the reaction proceeded very well with various arylalde-
hydes containing ortho-, meta-, and para-substituents on
the benzene ring to provide the corresponding chiral 1-
aryl propanols in 78–97% yields with high to outstanding
enantioselectivities (82.4–99.5% ee). The best asymmet-
ric induction of 99.5% ee was found using meta-chlo-
robenzaldehyde as substrate (Table 3, entry 5). The chiral
ligand 8e was also very effective in the enantioselective
addition of diethylzinc to a,b-unsaturated aliphatic alde-
hyde (Table 3, entry 9)
The ee was determined by HPLC using a chiral column with hex-
ane–i-PrOH as the eluent. HPLC was conducted on a JASCO model
PU-1580 intelligent HPLC pump and a JASCO model UV-1575 in-
telligent UV/Vis detector (254 nm). The injection loop had a 20 mL
capacity. The column used was a Chiralcel OD (250 × 4.6mm) from
Daicel Chemical Ind., Ltd (Japan). The column was operated at am-
bient temperature.
NMR Spectra (1H and 13C) were performed on a Bruker DPX 400
(400 MHz) spectrometer in CDCl3 (TMS as internal reference);
J values are given in Hz. IR Spectra were determined on a Therme
Nicolet IR 200 spectrophotometer. TLC was performed on dry sili-
ca gel plates with hexane–EtOAc as eluent. Mass spectra were ob-
tained using a Bruker esquire-3000 instrument with an electrospray
ionization source (ESIMS). All the ESIMS spectra were performed
with MeOH as the solvent.
Table 3 Asymmetric Addition of Diethylzinc to Aldehydes Using
Ligand 8ea
O
OH
Et2Zn, 5 mol% 8e
toluene, 0 °C, 48 h
R
H
R
Entry RCHO
Yield ee (%)c Configurationd
(%)b
Ferrocene-1,1¢-dicarboxaldehyde (4)
To a soln of 1,1¢-di(hydroxymethyl)ferrocene (1 g) in CHCl3 (10
mL) was added ‘active’ MnO2 (9.4 g).The reaction mixture was
heated under reflux for 4 h. The reaction was monitored by TLC
(petroleum ether–EtOAc, 1:1). The product mixture was filtered
and washed carefully with CHCl3 until the washings were colorless.
The solvent was removed under reduced pressure. The resulting res-
idue was recrystallized from Et2O–hexane to afford red crystal nee-
dles in 69% yield (0.69 g); mp 183 °C (lit.8 183–184 ºC).
1
2
3
4
5
6
7
8
9
C6H5CHO
p-MeC6H4CHO
91
78
86
96
84
88
98
97
68
92.6
87.0
92.3
82.4
99.5
91.7
90.9
90.1
87.0
S
S
S
S
S
S
S
S
S
m-MeOC6H4CHO
o-MeOC6H4CHO
m-ClC6H4CHO
IR (KBr): 3112, 1684, 1455, 1399, 1369, 1244, 1038, 834 cm–1.
m-BrC6H4CHO
Bis[(1S,2R)-2-hydroxy-1-methoxycarbonylpropyl]-1,1¢-ferro-
cenylmethyldiamine (6)
Heliotripine
Methyl L-threonine ester hydrochloride (2.9 g, 17.1 mmol) was dis-
solved in anhyd MeOH (30 mL) and cooled to 0 °C. Et3N (2.5 mL,
17.2 mmol) was added, and the reaction was stirred for 10 min. Fer-
rocene-1,1¢-dicarboxaldehyde 4 (1.8 g, 7.52 mmol) was added, the
reaction mixture was stirred for 1 h, and was monitored by TLC.
NaBH4 (1.14 g) was added portionwise to the reaction mixture over
a period of 0.5 h and the resulting mixture was stirred for 5 h. MeOH
was removed under reduced pressure at 40 °C. The resulting residue
was carefully neutralized with 3% HCl to pH 7–8 and then extracted
with EtOAc (3 × 20 mL). The combined ethereal extracts were
washed with brine (20 mL) and dried over Na2SO4. The solvent was
removed under reduced pressure. The resulting residue was purified
by preparative TLC (petroleum–EtOAc, 1:3) to afford 6 in 69%
yield (2.47 g); [a]D20 –55.0 (c 1.00, CHCl3).
Ferrocenecarboxaldehyde
C6H5CH=CHCHO
a Reagents: Et2Zn (2 equiv), aldehyde (1 equiv).
b Isolated yields.
c Determined by HPLC using a chiral OD column.
d Absolute was configuration assigned by comparison with the sign of
optical rotation of a known compound and known elution order from
a Chiralcel OD column.
In conclusion, chiral C2-symmetric 1,1¢-disubstituted fer-
rocenyl aziridino alcohols have been synthesized and ap-
plied as catalysts to promote enantioselective addition of
diethylzinc to aldehydes with good to excellent enantiose-
lectivity. The effect of the ligand structures on the enantio-
selectivity was then examined. Our results have
demonstrated that the introduction of C2-axial symmetry
led to a dramatic improvement in the enantioselectivity in
the addition of diethylzinc to benzaldehyde. Our results
also show that the C2-symmetric ferrocenyl b-amino alco-
hol ligands can produce an excellent asymmetric environ-
ment for asymmetric alkylation of aldehydes. Our efforts
to develop novel ferrocenyl aziridino alcohols as chiral
ligands for asymmetric synthesis are continuing, results
will be reported elsewhere.
IR (KBr): 3447, 3325, 3143, 2979, 2949, 2843, 1734, 1449, 1401,
1270, 1241, 1201, 1168, 1104, 1029, 992, 811 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.19 (d, J = 6 Hz, 6 H, 2 ×
CHCH3), 3.02 (d, J = 7.6 Hz, 2 H, 2 × COCH), 3.43 (d, J = 12.8 Hz,
2 H, 2 × NHCHH), 3.48 (d, J = 12.8 Hz, 2 H, 2 × NHCHH), 3.63
(m, 2 H, 2 × CH3CH), 3.72 (s, 6 H, 2 × OCH3), 4.08–4.11 (m, 6 H,
Fc), 4.17 (s, 2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 18.37, 46.72, 50.97, 66.65, 66.91,
67.28, 67.36, 67.49, 67.83, 85.30, 173.13.
MS (ESI): m/z = 499 [M + Na]+, 515 [M + K]+.
HRMS (MALDI): m/z calcd for C22H32FeN2O6 [M + Na]+,
499.1502; found, 499.1542.
Synthesis 2005, No. 20, 3620–3626 © Thieme Stuttgart · New York

3624
M.-C. Wang et al.
PAPER
1,1¢-Bis[(2S,3S)-2-methoxycarbonyl-3-methylaziridin-1-meth-
ylenyl]ferrocene (7)
resulting residue was purified by preparative TLC (hexane–EtOAc,
1:1) to give 8b in 55% yield (55 mg); [a]D20 –1.3 (c 0.638, CHCl3).
To a stirred soln of PPh3 (3.14 g, 12 mmol) in MeCN (63 mL) was
added CCl4 (18 mL). The soln turned yellow over a period of 0.5 h,
at which time 6 (952 mg, 2 mmol) was added dropwise in a soln of
Et3N (1.8 mL, 13 mmol) and MeCN (15 mL). The reaction mixture
was stirred for 2 h at 0 °C and then at r.t. for 14 h. The solvent was
removed under reduced pressure. The resulting residue was purified
by preparative TLC (petroleum ether–Et2O–Et3N, 3:6:1) to afford 7
in 77% yield (680 mg); [a]D20 –88.1 (c 1.01, CHCl3).
IR (KBr): 3500–2999, 2985, 2962, 2927, 2872, 2847, 1640, 1450,
1397, 1328, 1265, 1235, 1152, 1083, 1040, 926, 826 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.08 (s, 6 H, 2 × CH3), 1.16 (s, 6
H, 2 × CH3), 1.30 (d, J = 6 Hz, 6 H, 2 × CHCH3), 1.35 (d, J = 6.4
Hz, 2 H, 2 × NCH), 1.60–1.64 (m, 2 H, 2 × CHCH3), 2.89 (br s, 2
H, 2 × OH), 3.15(d, J = 12.8 Hz, 2 H, FcCH2), 3.52 (d, J = 12.8 Hz,
2 H, FcCH2), 4.04–4.08 (m, 6 H, Fc), 4.16 (d, J = 1.2 Hz, 2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 13.68, 25.62, 31.89, 40.01, 50.00,
59.54, 67.21, 68.45, 68.95, 69.32, 69.66, 84.77.
IR (KBr): 3106, 2999, 2953, 2933, 2823, 1746, 1439, 1395, 1361,
1327, 1291, 1261, 1235, 1196, 1176, 1147, 1122, 1056, 1025, 924,
825, 804 cm–1.
MS (ESI): m/z = 441 [M + H]+, 463 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 1.20 (d, J = 5.6 Hz, 6 H, 2 ×
CHCH3), 1.89–1.95 (m, 2 H, 2 × CH3CH), 2.18 (d, J = 6.8 Hz, 2 H,
2 × COCH), 3.32 (d, J = 13.2 Hz, 2 H, 2 × NCHH), 3.36 (d, J = 13.2
Hz, 2 H, 2 × NCHH), 3.70 (s, 6 H, 2 × OCH3), 4.05 (d, J = 0.8 Hz,
4 H, Fc), 4.11 (s, 4 H, Fc).
13C NMR (100 MHz, CDCl3): d = 13.17, 40.87, 41.79, 51.91, 58.65,
68.73, 68.82, 69.48, 69.64, 83.32,170.29.
Anal. Calcd for C24H36FeN2O2: C, 65.45; H, 8.24; N, 6.36. Found:
C, 65.58; H, 8.10; N, 6.27.
Aziridino Alcohols 8c–j; General Procedure
A Grignard reagent was prepared in the usual way from Mg (87 mg,
3.6 mmol) and alkyl bromide (3.6 mmol) in THF (5 mL). The soln
was cooled to –20 °C and then a soln of 7 (100 mg, 0.227 mmol) in
THF (1 mL) was added. The temperature of the reaction mixture
was allowed to reach r.t. and was stirred for 24 h. A sat. aq soln of
NH4Cl (10 mL) was added at 0 °C. The aqueous phase was extract-
ed with Et2O (3 × 10 mL). The combined organic phases were
washed with brine (15 mL), dried over Na2SO4, filtered, and the sol-
vent was removed under reduced pressure. The resulting residue
was purified by preparative TLC to afford 8c–j.
MS (ESI): m/z = 463 [M + Na]+, 479 [M + K]+.
HRMS (MALDI): m/z calcd for C22H28FeN2O4 [M + Na]+:
463.1291; found: 463.1291.
1,1¢-Bis[(2S,3S)-2-hydroxymethyl-3-methylaziridin-1-methyl-
enyl]ferrocene (8a)
To a stirred suspension of LiAlH4 (83 mg, 2.1 mmol) in anhyd THF
(4 mL), under N2, cooled to 0 °C, a soln of 7 (100 mg, 0.23 mmol)
in anhyd THF (2 mL) was added dropwise over 15 min. The result-
ing mixture was stirred for 8 h, then wet Et2O (10 mL) and a sat. aq
soln of NH4Cl (10 mL) were added carefully at 0 °C. The resultant
gel was filtered through glass wool and washed carefully with Et2O.
The filtrate was dried over Na2SO4 and the solvents were removed
under reduced pressure giving a orange red oil, which was further
purified by preparative TLC (hexane–EtOAc–MeOH, 2:2:1) to af-
1,1¢-Bis[(2S,3S)-2-diethylhydroxymethyl-3-methylaziridin-1-
methylenyl]ferrocene (8c)
Preparative TLC (hexane–EtOAc, 1:1) afforded 8c in 62% yield (70
mg); [a]D20 –28.3 (c 0.61, CHCl3).
IR (KBr): 3425, 3129, 2966, 2929, 1455, 1401, 1319, 1152, 1082,
1034, 972, 819 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.91–0.94 (m, 12 H, 4 × CH3),
1.30 (d, J = 6 Hz, 6 H, 2 × CHCH3), 1.25–1.55 (m, 10 H, 4 × CH2,
2 × NCH), 1.57–1.63 (m, 2 H, 2 × CHCH3), 2.93 (br s, 2 H, 2 × OH),
3.20 (d, J = 12.8 Hz, 2 H, 2 × FcCH2), 3.49 (d, J = 12.8 Hz, 2 H,
2 × FcCH2), 4.07 (d, J = 1.6 Hz, 6 H, Fc), 4.13 (d, J = 1.6 Hz, 2 H,
Fc).
20
ford 8a as a orange red oil in 66% yield (60 mg); [a]D +20.3 (c
1.08, CHCl3).
IR (KBr): 3481–3130, 3039, 3011, 2986, 2962, 1399, 1323, 1158,
1123, 1086, 1029, 955, 816 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.14 (d, J = 6 Hz, 6 H, 2 × CH3),
1.66–1.76 [m, 4 H, 2 × (CH)2N], 3.20 (d, J = 12.8 Hz, 2 H, 2 ×
CHHN), 3.34 (d, J = 12.8 Hz, 2 H, 2 × CHHN), 3.45 (dd, J = 7.2 Hz,
J = 4.4 Hz, 2 H, 2 × CHHOH), 3.68 (dd, J = 7.2, 4.4 Hz, 2 H, 2 ×
CHHOH), 4.08 (s, 4 H, Fc), 4.11 (d, J = 1.6 Hz, 2 H, Fc), 4.21 (s,
2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 7.74, 8.02, 14.15, 28.92, 32.81,
39.21, 47.63, 59.07, 68.47, 68.78, 69.13, 69.47, 68.84, 71.22, 84.71.
MS (ESI): m/z = 497 [M + H]+, 519 [M + Na]+.
Anal. Calcd for C28H44FeN2O2: C, 67.73; H, 8.93; N, 5.64. Found:
C, 67.68; H, 8.81; N, 5.72.
13C NMR (100 MHz, CDCl3): d = 13.29, 38.91, 44.18, 59.49, 60.10,
1,1¢-Bis[(2S,3S)-2-dipropylhydroxymethyl-3-methylaziridin-1-
methylenyl]ferrocene (8d)
68,63, 68.66, 68.98, 69.21, 85.00.
MS (ESI): m/z = 427 [M + Na]+, 443 [M + K]+.
Preparative TLC (hexane–EtOAc, 1:1) afforded 8d in 64% yield
Anal. Calcd for C20H28FeN2O2: C, 62.51; H, 7.34; N, 7.29. Found:
C, 62.55; H, 7.29; N, 7.26.
(80 mg); [a]D20 –16.1 (c 1.128, CHCl3).
IR (KBr): 3429, 3093, 2957, 2930, 2871, 1456, 1403, 1378, 1326,
1265, 1235, 1149, 1123, 1086, 1037, 1025, 1000, 925, 907, 825,
812 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.86–0.92 (m, 12 H, 4 × CH2CH3),
1.31 (d, J = 6 Hz, 6 H, 2 × CHCH3), 1.32–1.46 (m, 18 H, 4 ×
CH2CH2CH3, 2 ×NCH), 1.57–1.60 (m, 2 H, 2 × CH3CH), 2.94 (s, 2
H, 2 × OH), 3.23 (d, J = 12.8 Hz, 2 H, 2 × CHHN), 3.44 (d, J = 12.8
Hz, 2 H, 2 × CHHN), 4.06–4.08 (m, 6 H, Fc), 4.13 (s, 2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 14.25, 14.71, 14.92, 16.74, 16.98,
39.48, 43.78, 48.26, 59.21, 68.52, 68.86, 69.18, 69.55, 71.01, 84.83.
MS (ESI): m/z = 553 [M + H]+.
1,1¢-Bis[(2S,3S)-2-dimethylhydroxymethyl-3-methylaziridin-1-
methylenyl]ferrocene (8b)
A Grignard reagent was prepared in the usual way from Mg (87 mg,
3.6 mmol) and MeI (0.224 mL, 3.6 mmol) in Et2O (5 mL). The soln
was cooled to 0 °C and a soln of 7 (100 mg, 0.227 mmol) in Et2O (2
mL) was added. The reaction mixture was stirred for 3 h at 0 °C and
then heated at reflux for 5 h. The reaction was quenched by the ad-
dition of a sat. aq soln of NH4Cl (10 mL) at 0 °C. The aqueous phase
was separated and extracted with Et2O (3 × 10 mL). The combined
organic phases were washed with brine (10 mL), dried over Na2SO4,
filtered, and the solvent was removed under reduced pressure. The
Anal. Calcd for C32H52FeN2O2: C, 69.55; H, 9.48; N, 5.07. Found:
C, 69.44; H, 9.69; N, 4.85.
Synthesis 2005, No. 20, 3620–3626 © Thieme Stuttgart · New York

PAPER
Ferrocenyl Aziridino Alcohol Ligands
3625
1,1¢-Bis[(2S,3S)-2-diisopropylhydroxymethyl-3-methylaziridin-
1-methylenyl]ferrocene (8e)
IR (KBr): 3434, 3095, 2953, 2930, 2863, 1460, 1403, 1380, 1327,
1265, 1155, 1125, 1086, 1038, 822 cm–1.
Preparative TLC (hexane–EtOAc, 2:1) afforded 8e in 62% yield (78
1H NMR (400 MHz, CDCl3): d = 0.88–0.94 (m, 12 H, 4 × CH2CH3),
1.21–1.50 [m, 40 H, 4 × (CH2)4, 2 × CHCH3, 2 × NCH], 1.58–1.62
(m, 2 H, 2 × CH3CH), 2.93 (br s, 2 H, 2 × OH), 3.27 (d, J = 12.8 Hz,
2 H, 2 × CHHN), 3.41 (d, J = 12.8 Hz, 2 H, 2 × CHHN), 4.07 (d,
J = 1.2 Hz, 6 H, Fc), 4.13 (s, 2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 14.09, 14.15, 22.62, 22.71, 23.10,
23.38, 32.43, 32.64, 36.95, 41.24, 39.60, 48.31, 59.18, 68.54, 68.92,
69.25, 71.03, 84.77.
mg); [a]D20 –48 (c 0.68, CHCl3).
IR (KBr): 3422, 3118, 2962, 2935, 2879, 1643, 1399, 1326, 1274,
1155, 1126, 1087, 1026, 924, 823 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.97–1.01 (m, 24 H, 8 × CH3),
1.29 (d, J = 6 Hz, 6 H, 2 × CHCH3), 1.47 (d, J = 6.4 Hz, 2 H, 2 ×
NCH), 1.51–1.54 (m, 2 H, 2 × CH3CH), 1.90–2.02 [m, 4 H, 4 ×
CH(CH3)2], 2.79 (d, J = 13.9 Hz, 2 H, CHHN), 3.97 (d, J = 13.9 Hz,
2 H, CHHN), 2.86 (s, 2 H, 2 × OH), 4.09–4.10 (m, 6 H, Fc), 4.15 (s,
2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 15.27 15.32, 17.86, 18.05, 18.17,
18.38, 34.43, 35.59, 38.37, 45.24, 58.38, 68.76, 69.17, 69.42, 74.75,
84.67.
MS (ESI): m/z = 665 [M + H] +, 687 [M + Na] +.
Anal. Calcd for C40H68FeN2O2: C, 72.26; H, 10.31; N, 4.21. Found:
C, 72.38; H, 10.23; N, 4.06.
1,1′-Bis[(2S,3S)-2-di-iso-pentylhydroxymethyl-3-methylaziri-
din-1-methylenyl]ferrocene (8i)
MS (ESI): m/z = 553 [M + H]+.
Preparative TLC (hexane–EtOAc, 3.5:1) afforded 8i in 64% yield
Anal. Calcd for C32H52FeN2O2: C, 69.55; H, 9.48; N, 5.07. Found:
C, 69.53; H, 9.74; N, 4.79.
(96 mg); [a]D20 –12.7 (c 0.96, CHCl3).
IR (KBr): 3423, 3117, 2954, 2929, 2925, 2869, 1466, 1401, 1367,
1325, 1265, 1234, 1156, 1124, 1085, 1037, 1025, 923, 824, 812
cm–1.
1,1¢-Bis[(2S,3S)-2-dibutylhydroxymethyl-3-methyl-aziridin-1-
methylenyl]ferrocene (8f)
Preparative TLC (hexane–EtOAc, 4:1) afforded 8f in 58% yield (80
1H NMR (400 MHz, CDCl3): d = 0.85–0.91 (m, 24 H, 8 × CH3),
1.33 (d, J = 6.8 Hz, 6 H, 2 × CHCH3), 1.16–1.50 (m, 22 H, 4 ×
CH2CH2CH, 2 × NCH), 1.58–1.61 (m, 1 H, CH3CH), 2.93 (s, 2 H,
2 × OH), 3.31 (d, J = 12.8 Hz, 2 H, 2 × CHHN), 3.36 (d, J = 12.8
Hz, 2 H, 2 × CHHN), 4.06–4.08 (m, 6 H, Fc), 4.14 (s, 2 H, Fc).
13C NMR (100 MHz, CDCl3):d = 14.23, 22.49, 22.54, 22.66, 22.79,
28.56 28.64, 32.25, 32.69, 34.50, 38.84, 39.59, 48.30, 59.29, 68.49,
68.92, 69.23, 70.98, 84.81.
mg); [a]D20 –14.9 (c 1.43, CHCl3).
IR (KBr): 3434, 3100, 2955, 2932, 2862, 1458, 1403, 1379, 1326,
1263, 1234, 1154, 1123, 1058, 1073, 1005, 822 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.87–0.92 (m, 12 H, 4 × CH2CH3),
1.36 (d, J = 5.6 Hz, 6 H, 2 × CH3), 1.24–1.35 [m, 24 H, 4 × (CH2)3],
1.52 (d, J = 6.8 Hz, 2 H, 2 × NCH), 1.71–1.74 (m, 2 H, 2 × CH3CH),
3.14 (d, J = 12.8 Hz, 2 H, CHHN), 3.59 (d, J = 12.8 Hz, 2 H,
CHHN), 4.08–4.11 (m, 6 H, Fc), 4.16 (d, J = 0.8 Hz, 2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 13.66, 14.06, 14.14, 23.23, 23.43,
25.58, 25.82, 36.27, 40.78, 40.22, 48.78, 58.43, 67.25, 68.78, 69.21,
69.49, 69.78, 71.10, 83.79.
MS (ESI): m/z = 665 [M + H]+, 687 [M + Na]+.
Anal. Calcd for C40H68FeN2O2: C, 72.26; H, 10.31; N, 4.21. Found:
C, 72.11; H, 10.52; N, 4.15.
MS (ESI): m/z = 609 [M + H]+, 631 [M + Na]+.
1,1¢-Bis[(2S,3S)-2-diphenylhydroxymethyl-3-methylaziridin-1-
methylenyl]ferrocene (8j)
Preparative TLC (hexane–EtOAc, 4:1) afforded 8j in 88% yield
(137 mg); mp 188 °C; [a]D +54.8 (c 0.99, CHCl3).
Anal. Calcd for C36H60FeN2O2: C, 71.03; H, 9.94; N, 4.60. Found:
C, 71.32; H, 9.78; N, 4.42.
1,1¢-Bis[(2S,3S)-2-di-iso-butylhydroxymethyl-3-methylaziri-
din-1-methylenyl]ferrocene (8g)
IR (KBr): 3375–3088, 3058, 3027, 2990, 2953, 2925, 2852, 1599,
1490, 1449, 1405, 1330, 1266, 12378, 1170, 1080, 1015, 813, 728,
700 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.01 (d, J = 5.4 Hz, 6 H, 2 × CH3),
1.83–1.87 (m, 2 H, 2 × CH3CH), 2.32 (d, J = 6.4 Hz, 2 H, 2 ×
CH3CHCH), 3.30 (d, J = 12.8 Hz, 2 H, 2 × CHHN), 3.39 (d,
J = 12.8 Hz, 2 H, 2 × CHHN), 3.80 (s, 2 H, Fc), 3.92 (d, J = 0.8 Hz,
2 H, Fc), 4.00 (s, 4 H, Fc), 4.56 (s, 2 H, 2 × OH), 7.15–7.48 (m, 20
H, Ph).
Preparative TLC (hexane–EtOAc, 4:1) afforded 8g in 53% yield (73
mg); [a]D20 –19.9 (c 0.52, CHCl3).
IR (KBr): 3421, 3133, 2953, 2936, 2868, 1460, 1401, 1324, 1157,
1124, 1086, 1037, 825 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.94 (m, 24 H, 8 × CH3), 1.32 (d,
J = 5.6 Hz, 6 H, 2 × CHCH3), 1.26–1.51 (m, 10 H, 4 × CH2,
2 × NCH), 1.58–1.61 (m, 2 H, 2 × CH3CH), 1.73–1.83 (m, 4 H, 4 ×
CH), 2.98 (s, 2 H, 2 × OH), 3.16 (d, J = 12.8 Hz, 2 H, 2 × CHHN),
3.55 (d, J = 12.8 Hz, 2 H, 2 × CHHN), 4.09 (d, J = 4.4 Hz, 6 H, Fc),
4.13 (s, 2 H, Fc).
13C NMR (100 MHz, CDCl3): d = 13.51, 39.77, 50.74, 58.57, 68.71,
69.01, 69.37, 84.26, 73.59, 125.90, 126.37, 126.41, 126.79,127.88,
128.04.
13C NMR (100 MHz, CDCl3): d = 14.19, 23.89, 24.12, 24.83, 24.87,
25.08, 39.83, 46.41, 49.51, 50.21, 59.15, 68.55, 68.86, 69.11, 69.50,
72.24, 84.96.
MS (ESI): m/z = 689 [M + H]+, 711 [M + Na]+.
Anal. Calcd for C44H44FeN2O2 requires: C, 76.74; H, 6.44; N, 4.07.
Found: C, 76.71; H, 6.57; N, 4.05.
MS (ESI): m/z (%) = 609 [M + H]+, 631 [M + Na]+.
Enantioselective Addition of Et2Zn to Arylaldehydes; General
Procedure
Anal. Calcd for C36H60FeN2O2: C, 71.03; H, 9.94; N, 4.60. Found:
C, 71.21; H, 9.68; N, 4.35.
A soln of Et2Zn (1 M, hexane; 1.1 mL) was added to a soln of a
chiral catalyst (0.025 mmol, 5 mol%) in anhyd toluene under a ni-
trogen atmosphere. The mixture was cooled to 0 °C and stirred for
30 min. Freshly distilled benzaldehyde (0.05 mL, 0.5 mmol) was
added to the mixture. The resulting mixture was stirred at 0–5 °C for
10 h, then allowed to warm to r.t. and stirring was continued for an
additional 38 h. The reaction was quenched by the addition of a sat.
1,1¢-Bis[(2S,3S)-2-dipentylhydroxymethyl-3-methylaziridin-1-
methylenyl]ferrocene (8h)
Preparative TLC (hexane–EtOAc, 4:1) afforded 8h in 73% yield
(110 mg); [a]D20 –15.8 (c 1.12, CHCl3).
Synthesis 2005, No. 20, 3620–3626 © Thieme Stuttgart · New York

3626
M.-C. Wang et al.
PAPER
aq soln of NH4Cl (4 mL) and extracted with Et2O (3 × 8 mL). The
combined organic layers were washed with brine (8 mL), dried over
anhyd Na2SO4, and the solvent was removed under reduced pres-
sure. Purification of the residue by preparative TLC (hexane–
EtOAc, 4:1) afforded the (S)-1-phenyl-1-propanol. The ee was de-
termined by HPLC analysis using a chiral column.
Tetrahedron: Asymmetry 2003, 14, 1763. (m) Da, C.; Han,
Z.; Ni, M.; Yang, F.; Liuj, D.; Zhou, Y.; Wang, R.
Tetrahedron: Asymmetry 2003, 14, 659. (n) Oliveira, L. F.;
Costa, V. E. U. Tetrahedron: Asymmetry 2004, 15, 2583.
(o) Fonseca, M. H.; Eibler, E.; Zabel, M.; Konig, B.
Tetrahedron: Asymmetry 2003, 14, 1989. (p) Lesma, G.;
Danieli, B.; Passarella, D.; Sacchitti, A.; Silvani, A.
Tetrahedron: Asymmetry 2003, 14, 2453. (q) Ko, D.-H.;
Kim, K. H.; Ha, D.-C. Org. Lett. 2002, 4, 3759.
X-Ray Crystallographic Study
An orange-red crystal of approximate dimensions 0.20 ×
0.18 × 0.16 mm was mounted on a glass fiber. Crystallographic data
for 8j were measured on a Rigaku RAXIS-IV imaging plate area de-
tector. The data were collected at 291(2) K using graphite mono-
chromated Mo Ka(l = 0.71073 Å), 2.03°<q<27.51°. The structures
were solved by a direct method and expanded using Fourier tech-
niques. The non-hydrogen atoms were refined anisotropically. Hy-
drogen atoms were included but not refined. All calculations were
performed using the teXsan crystallographic software package.
Crystal data for 8j: Monoclinic P21: a = 10.171 (2), b = 17.682 (4),
c = 10.374 (2) Å, d = 105.13 (3)°; V = 1801.1(6) Å3; formula unit
C44H44FeN2O2 with Z = 2; Dcalcd = 1.270 gcm–3; F(000) = 728;
m(MoKa) = 0.458 mm–1. Full-matrix least-squares refinement on F2
based on 6067 independent reflections (Rint = 0.0249) converged
with 452 parameters. Final R indices [I>2s(I)]: R1 = 0.0460,
wR2 = 0.0982; R indices (all data): R1 = 0.0730, wR2 = 0.1050;
GoF = 0.985.
(3) For review see: (a) Whitesell, J. K. Chem. Rev. 1989, 89,
1581. (b) Ward, R. S. Chem. Soc. Rev. 1990, 1. (c) Fache,
F.; Schulz, E.; Tommasino, M. L.; Lemaire, M. Chem. Rev.
2000, 100, 2159. (d) Seebach, D.; Beck, A. K.; Heckel, A.
Angew. Chem. Int. Ed. 2001, 40, 92. (e)Chen, Y.;Yekta, S.;
Yudin, A. K. Chem. Rev. 2003, 103, 3155. (f) Kočovský,
P.; Vyskočil, Š.; Smrčina, M. Chem. Rev. 2003, 103, 3213.
(g) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029.
(4) For review see: (a) Richards, C. J.; Locke, A. J.
Tetrahedron: Asymmetry 1998, 9, 2377. (b) Sutcliffe, O. B.;
Bryce, M. R. Tetrahedron: Asymmetry 2003, 14, 2297.
(c) Colacot, T. J. Chem. Rev. 2003, 103, 3101.
(5) (a) Bastin, S.; Delebecque, N.; Agbossou, F.; Brocard, J.;
Pélinski, L. Tetrahedron: Asymmetry 1999, 10, 1647.
(b) Bastin, S.; Agbossou-Niedercorn, F.; Brocard, J.;
Pélinski, L. Tetrahedron: Asymmetry 2001, 12, 2399.
(6) (a) Andersson, P. G.; Guijarro, D.; Tanner, D. J. Org. Chem.
1997, 62, 7364. (b) Tanner, D.; Kornø, H. T.; Guijarro, D.;
Andersson, P. G. Tetrahedron 1998, 54, 14213.
Acknowledgment
(c) Lawrence, C. F.; Nayak, S. K.; Thijs, L.; Zwanenburg, B.
Synlett 1999, 1571. (d) ten Holte, P.; Wijgergangs, J.-P.;
Thijs, L.; Zwanenburg, B. Org. Lett. 1999, 1, 1095. (e) Shi,
M.; Jiang, J.-K.; Feng, Y.-S. Tetrahedron: Asymmetry 2000,
11, 4923. (f) Bulman Page, P. C.; Allin, S. M.; Maddocks, S.
J.; Elsegood, M. R. J. J. Chem. Soc., Perkin Trans. 1 2002,
36, 2827. (g) Shadakshari, U.; Nayak, S. K. Tetrahedron
2001, 57, 8185. (h) Tanner, D.; Harden, A.; Johansson, F.;
Wyatt, P.; Andersson, P. G. Acta Chem. Scand. 1996, 50,
361.
We are grateful to the National Natural Sciences Foundation of
China (NNSFC: 20172047), Henan Outstanding Youth Program
2001, and the Education Department of Henan Province for
financial support.
References
(1) (a) Lin, G.-Q.; Li, Y.-M.; Chan, A. S. C. Principle and
Application of Asymmetric Synthesis; Wiley-Interscience /
John Wiley and Sons: New York, 2001. (b) Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H. Comprehensive Asymmetric
Catalysis; Springer-Verlag: Berlin, 1999. (c) Noyori, R.
Asymmetric Catalysis in Organic Synthesis; Wiley: New
York, 1994. (d) Ojima, I. Catalytic Asymmetric Synthesis;
VCH: New York, 1993.
(7) (a) Wang, M.-C.; Wang, D.-K.; Zhu, Y.; Liu, L.-T.; Guo, Y.-
F. Tetrahedron: Asymmetry 2004, 15, 1289. (b) Wang, M.-
C.; Liu, L.-T.; Zhang, J.-S.; Shi, Y.-Y.; Wang, D.-K.
Tetrahedron: Asymmetry 2004, 15, 3853. (c) Wang, M.-C.;
Wang, D.-K.; Lou, J.-P.; Hua, Y.-Z. Chin. J. Chem. 2004,
22, 512.
(2) Reviews on enantioselective organozinc additions to
aldehydes: (a) Noyori, R.; Kitamura, M. Angew. Chem., Int.
Ed. Engl. 1991, 30, 49. (b) Soai, K.; Niwa, S. Chem. Rev.
1992, 92, 833. (c) Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101,
757. For selected recent papers for asymmetric alkylation of
aldehydes, see: (d) Couty, F.; Prim, D. Tetrahedron:
Asymmetry 2002, 13, 2619. (e) Hermsen, P. J.; Cremers, J.
G. O.; Thijs, L.; Zwanenburg, B. Tetrahedron Lett. 2001, 42,
4243. (f) Bastin, S.; Ginj, M.; Brocard, J.; Pelinski, L.;
Novogrocki, G. Tetrahedron: Asymmetry 2003, 14, 1701.
(g) Vilaplana, M. J.; Molina, P.; Arques, A.; Andres, C.;
Pedrosa, R. Tetrahedron: Asymmetry 2002, 13, 5. (h) Chen,
Y.-J.; Lin, R.-X.; Chen, C. Tetrahedron: Asymmetry 2004,
15, 3561. (i) Li, M.; Yuan, K.; Li, Y.-Y.; Cao, B.-X.; Sun, J.;
Hou, X.-L. Tetrahedron: Asymmetry 2003, 14, 3347.
(j) Wu, X.-W.; Zhang, T.-Z.; Yuan, K.; Hou, X.-L.
Tetrahedron: Asymmetry 2004, 15, 2357. (k) Nugent, W. A.
Org. Lett. 2002, 4, 2133. (l) Joshi, S. N.; Malhotra, S. V.
(8) Osgerby, J. M.; Pauson, P. L. J. Chem. Soc. 1961, 4604.
(9) Hauser, C. R.; Lindsay, J. R.; Lednicer, D.; Cain, C. E. J.
Org. Chem. 1957, 22, 717.
(10) Crystallographic data for the structure reported in this paper
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-
272339. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, CAMBRIDGE, CB2
1EZ, UK [fax: +44(1223)336033, e-mail:
deposit@ccdc.cam.ac.uk].
(11) Sibi, M. P.; Chen, J.; Cook, G. R. Tetrahedron Lett. 1999,
40, 3301.
(12) Yang, X.; Shen, J.; Da, C.; Wang, R.; Choi, M. C. K.; Yang,
L.; Wong, K. Tetrahedron: Asymmetry 1999, 10, 133.
(13) Mayers, A.; Schmidt, W.; Mcdennon, M. J. Synthesis 1993,
250.
Synthesis 2005, No. 20, 3620–3626 © Thieme Stuttgart · New York