Ferrosalen and ferrosalen-type ligands: Structural modulation and applications in asymmetric catalysis

Article abstract of DOI:10.1021/om2002206

Several ferrosalen and ferrosalen-type ligands, 1-10, were prepared and fully characterized. The structure of one of these ligands ligated to Cu(II) was determined by single-crystal X-ray diffraction analysis. In comparison with the parent ligand 1, the two six-membered rings of ligand 2 are not aromatized and the synthesis was more facile. Diastereoisomers 3 and 4, containing substituents on the ethylene chain, were synthesized. The aromatized versions of 3 and 4, namely 5 and 6, were also prepared. Further modulation of the ethylene backbone produced ligands 7 and 8. Replacing the Cp ligands with Cp* and Cp ^Ph5 gave ligands 9 and 10, respectively. All these ligands were tested for catalytic asymmetric reactions, including the Co(III)-catalyzed carbonyl-ene reaction, Al(III)-catalyzed Strecker reaction, and Al(III)-catalyzed silylcyanation of aldehyde.

Full text of DOI:10.1021/om2002206

ARTICLE
pubs.acs.org/Organometallics
Ferrosalen and Ferrosalen-Type Ligands: Structural Modulation and
Applications in Asymmetric Catalysis
Xiang Zhang, Rudy L. Luck, and Shiyue Fang*
Department of Chemistry, Michigan Technological University, 1400 Townsend Drive, Houghton, Michigan 49931, United States
S Supporting Information
b
ABSTRACT: Several ferrosalen and ferrosalen-type ligands,
1ꢀ10, were prepared and fully characterized. The structure of
one of these ligands ligated to Cu(II) was determined by single-
crystal X-ray diffraction analysis. In comparison with the parent
ligand 1, the two six-membered rings of ligand 2 are not
aromatized and the synthesis was more facile. Diastereoisomers
3 and 4, containing substituents on the ethylene chain, were
synthesized. The aromatized versions of 3 and 4, namely 5 and 6,
were also prepared. Further modulation of the ethylene backbone
produced ligands 7 and 8. Replacing the Cp ligands with Cp* and
CpPh5 gave ligands 9 and 10, respectively. All these ligands were
tested for catalytic asymmetric reactions, including the Co(III)-
catalyzed carbonyl-ene reaction, Al(III)-catalyzed Strecker reaction, and Al(III)-catalyzed silylcyanation of aldehyde.
’ INTRODUCTION
Salen and salen-type ligands have been widely used in asym-
metric catalysis. Most of these ligands were rendered chiral by
introduction of two central chiral centers at the 8- and 80-positions in
their backbone. To solve certain selected problems such as en-
antioselective epoxidation of conjugated cis-olefins and unfunctio-
nalized olefins, Katsuki’s group designed and synthesized salen
ligands that contain central or axial chiral centers at the 3- and 30-
positions.1 Recently, salen and salen-type ligands that contain the
Figure 1. The two structural motifs of a new class of chiral ligands.
planar chiral ferrocenyl moieties were also reported in the literature.
For example, Ballistreri and co-workers used ferrocene-containing
diamines for salen-type ligand synthesis. The resulting ligands
contained one or more ferrocenyl groups in their backbone.2
Bildstein’s group incorporated one or more ferrocenyl groups into
the front part of salen-type ligands.3 Erker’s group used hydro-
xyferrocene as the building block for salen-type ligand synthesis. In
this case, the bulky FeCp groups are very close to the catalytic center,
which may be beneficial for stereocontrol.4
Three years ago, we started to develop a new class of chiral
ferrocenyl ligands based on two common structural motifs
(Figure 1). Our preliminary results showed that such ligands
are chemically and configurationally stable and are compatible with
several catalytic reaction conditions.5 More recently, we have success-
fully developed a stereoselective method to access this class of ligands
such as 1 (Figure 2). As a result, we no longer need to rely on chiral
HPLC resolution to obtain them in enantiopure form, and gram-
sized quantities can be synthesized conveniently.6 In addition, this
synthetic route provided an opportunity to modulate the steric
hindrance at the ethylene backbone and at the FeCp groups. In
this paper, we wish to report the synthesis and characterization of
ligands 2ꢀ10 (Figure 2) and their use for the Co(III)-catalyzed
carbonyl-ene reaction, Al(III)-catalyzed Strecker reaction, and
Al(III)-catalyzed silylcyanation of aldehyde.
’ RESULTS AND DISCUSSION
The synthesis of ligand 1 (both enantiomers are accessible)
has been reported previously.6 Ligand 2 is the unaromatized version
of 1. As the synthesis of 2 is several steps shorter, it was prepared to
evaluate usefulness in asymmetric catalysis. This unaromatized
ligand may also display useful electronic and steric properties in
catalysis. As shown in Scheme 1, enantiopure 11 (both enantiomers
are accessible; the R enantiomer was used)6 was condensed with
1,2-diaminoethane in anhydrous methanol at room temperature.7
Ligand 2 was obtained in quantitative yield as a red foam. Stirring 2
with cupric acetate in a solvent mixture of ethanol and water at room
temperature gave the Cu(II) complex 12 in 75% yield (Scheme 1).8
Compound 12 is paramagnetic and was not characterized by NMR,
but HRMS contained a peak equal to the calculated molecular
Received: March 10, 2011
Published: April 11, 2011
r
2011 American Chemical Society
2609
dx.doi.org/10.1021/om2002206 Organometallics 2011, 30, 2609–2616
|

Organometallics
ARTICLE
Figure 2. Ferrosalen and ferrosalen-type ligands.
this is typical for ferrocenyl compounds. One would predict that
the aromatized compounds (5ꢀ8) would be less stable than the
unaromatized ones (2ꢀ4) due to the reduced aromaticity of
their ferrocenyl units. However, we did not observe any obvious
difference in their stabilities in the solid state as well in solution.
Our attempts to obtain crystals of these ligands chelating to metal
centers such as Cu(II), Co(II), and Ru(II) complexes for X-ray
diffraction analysis have not been successful so far.
Scheme 1. Synthesis of Ligand 2 and the Cu(II) Complex 12
A significant advantage of using the FeCp group in ligands to
control stereoselectivity of catalytic reactions is the ability to
modulate its size. For example, the Cp group can be changed to
Cp* (C5Me5) and CpPh5 (C5Ph5). With these more bulky
groups, the apical positions of the catalytic center of the
ferrosalen-metal complex may be shielded to varying degrees,
which may only allow substrates to react through one specific
pathway. In order to evaluate this, enantiopure 9 and 10 were
synthesized (Scheme 3). For the synthesis of 9, compound 16a11
was reacted with succinic anhydride in the presence of AlCl3 to
give the ferrocenyl ketone 17a. Reduction of the ketone with Zn/
HgCl2 resulted in compound 18a. Compound 18a was cyclized
through an intramolecular FriedelꢀCrafts reaction using trifluor-
oacetic anhydride as the activation agent to give the racemic
ferrocenyl cyclohexanone 19a. To resolve the enantiomers,
commercially available enantiopure (þ)-20 was deprotonated
with n-BuLi and the resulting anion reacted with ketone 19a to
give diastereoisomers 21xa and 21ya. These isomers could be
resolved on TLC with Rf values being 0.55 and 0.40, respectively,
when the developing solvent mixture was hexanes/ether (1/1).
However, we only obtained 21xa in pure form. During flash
column chromatography, 21xa and 21yb slowly decomposed to
give 20 and the parent ketones (þ)- and (ꢀ)-19; the other
diastereoisomer 21ya was contaminated with ketones and could
not be purified. Pure 21xa was decomposed in refluxing toluene
to give enantiopure (þ)-19a.6,12 Formylation of 19a with ethyl
weight. We were also successful in growing crystals for X-ray
diffraction analysis (Figure 3). In the solid-state structure, like most
metallosalen complexes in the absence of multidentate ancillary
ligands, 12 adopts a trans configuration. Although there is no
substituent at the ethylenediamine backbone, the five-membered
ring containing Cu(II) and two nitrogen atoms are in a half-chair
conformation. This produces an overall stepped conformation for
the metallosalen complex.9
Ligands 3 and 4 are diastereoisomers. In catalytic applications,
they should display different efficiencies in stereocontrol. Their
syntheses were achieved by condensing the commercially avail-
able enantiopure 13 with (þ)- and (ꢀ)-11 in anhydrous metha-
nol, respectively (Scheme 2). Good isolated yields were ob-
tained. Ligands 5 and 6 are also diastereoisomers. They are the
aromatized version of compounds 3 and 4. Their syntheses were
accomplished under similar conditions for the synthesis of 3 and
4 using (þ)-13 and the two enantiomers of compound 14
(Scheme 2).6 The ethylenediamine backbone of ferrosalen 5
and 6 was changed to 1,2-diaminocyclohexane (15) to give
ligands 7 and 8 (Scheme 2) utilizing similar synthetic conditions.
Ligands 3ꢀ8 were fully characterized by 1H and 13C NMR and
HRMS. They are stable deep red crystalline solids, and in
solution, they are stable under inert atmospheres. Upon exposure
to air, the solutions turn green, indicating oxidation occurred;
2610
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616

Organometallics
ARTICLE
Figure 3. ORTEP-310 structure of 12. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented by circles of arbritary
radii. Selected bond lengths (Å) and angles (deg) for 12: Fe1ꢀC1 = 2.012(12), Fe1ꢀC2 = 2.041(14), Fe1ꢀC3 = 2.006(14), Fe1ꢀC4 = 2.024(11),
Fe1ꢀC5 = 2.028(11), Fe1ꢀC6 = 2.023(11), Fe1ꢀC7 = 2.009(12), Fe1ꢀC8 = 2.037(11), Fe1ꢀC9 = 2.067(10), Fe1ꢀC10 = 2.082(11), Cu1ꢀO1 =
1.927(7), Cu1ꢀN1 = 1.936(8), N1ꢀC15 = 1.326(14), N1ꢀC16 = 1.453(13); O1ꢀCu1ꢀO10 = 91.8(4), O1ꢀCu1ꢀN10 = 165.6(3), O1ꢀCu1ꢀN1 =
1
93.9(4), N10ꢀCu1ꢀN1 = 83.7(6). Equivalent atoms (denoted by a prime) generated by ꢀx þ 2, ꢀx þ y þ 1, ꢀz þ /3.
formate in the presence of sodium hydride gave 22a, which was
condensed with 1,2-diaminoethane in anhydrous methanol to
give ligand (þ)-9.
reaction, the best ee was 26% in an 89% yield. This was achieved using
(þ)-3-AlCl as the catalyst at a loading of 5 mol %. The configuration
of the major enantiomer is S.14 With (þ)-5-AlCl as catalyst and
under similar conditions, the selectivity and yield were lowered to
18% ee and 84%, respectively. We believe that the low ee's obtained
with ligands 1ꢀ10 can be attributed in part to the lack of steric
hindrance at the 5- and 50-positions. Without any bulky groups at
these positions, a large area at the side opposite to the FeCp group is
open. Assuming that there are no secondary interactions between the
substrates and the catalysts, the conformations of the transition states
are flexible.
For the synthesis of 10, compound 16b was prepared accord-
ing to a modified literature procedure.13 This compound was
converted to racemic 19b following the same sequence of reactions
used for the preparation of 19a. Racemic 19b was then resolved using
(þ)-20 according to the procedure described for resolution of 19a.
The two diastereoisomers 21xb and 21yb have Rf values of 0.35 and
0.20, respectively, when the developing solvent mixture was hexanes/
ether (2/1). Similar to compounds 21xa and 21ya, these two dias-
tereoisomers were not stable; they decompose slowly, resulting in 20
and the parent ketones (þ)- and (ꢀ)-19. Because 21xb has an Rf
value similar to that of ketone 19, we were only able to obtain pure
21yb. Removal of the chiral auxiliary 20 from 21yb in refluxing
toluene gave enantiopure (ꢀ)-19b (Scheme 3). At this time, we
were not able to obtain enantiopure (þ)-19b. With enantiopure
(ꢀ)-19b in hand, the synthesis of (ꢀ)-10 was straightforward, even
though the highly bulky FeCpPh5 group could have hindered the
synthesis during the formylation and imine formation reactions. For
formylation, compound 22b was obtained in 77% yield. Condensa-
tion of 22b with 1,2-diaminoethane gave ligand (ꢀ)-10 in 68% yield
(Scheme 3).
All the ligands (1ꢀ10) were tested in the Co(III)-catalyzed
carbonyl-ene reaction (eq 1), Al(III)-catalyzed Strecker reaction
(eq 2; for ease of isolation, the product was acylated with benzoyl
chloride), and Al(III)-catalyzed silylcyanation of aldehyde (eq 3).
Under the conditions we have investigated, all reactions resulted in
good yields but unsatisfactory enantioselectivity. The best selectivity
we achieved for the carbonyl-ene reaction was 29% using (ꢀ)-8-
Co(III) as the catalyst with a 5 mol % loading and with a 78% yield.
The major enantiomer has an R configuration. Using (þ)-7, a
diastereoisomer of (ꢀ)-8, as the ligand, under the same conditions,
the ee was 10% but the yield was higher at 99%. In this case, the major
enantiomer had an Sconfiguration. For the Strecker reaction, the best
ee we obtained was 20%. The catalyst used was (ꢀ)-1-AlCl gene-
rated in situ with 10 mol % ligand and 9 mol % Et2AlCl. Under these
conditions, the yield was quantitative. For the aldehyde silylcyanation
In conclusion, we have synthesized and fully characterized
nine enantiopure ferrosalen ligands and investigated their appli-
cations in enantioselective carbonyl-ene, Strecker, and silylcya-
nation of aldehyde reactions. All the ligands are compatible with
these reaction conditions, and high yields were obtained. How-
ever, the enantionselectivity was low under the conditions we
tested. The low selectivity may be a result of the lack of steric
hindrance at the 5- and 50-positions of the ligands. Future work
will be directed to the modulation of steric hindrance at these
2611
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616

Organometallics
ARTICLE
positions and to the evaluation of the resulting new ligands for
catalytic enantioselective reactions.
1H and 13C NMR spectra were measured at 400 and 100 MHz, respectively;
chemical shifts (δ) were reported in reference to solvent peaks (residue
CHCl3 at δ 7.24 ppm for 1H and CDCl3 at δ 77.00 ppm for 13C, C6D5H at
δ7.16 ppm for 1HandC6D6 at δ128.4 ppm for 13C). GC-MS were measured
on a Shimadzu GCMS-QP5050A instrument: column, DB-5MS; thickness,
0.25 μm; diameter, 0.25 mm; length, 25 m; MS, positive EI. HPLC was
performed on a JASCO LC-2000Plus System: pump, PU-2089Plus Qua-
ternary Gradient; detector, UV-2075Plus; chiral analytical column, Chiracel
AS-H (5 μm diameter, 100 Å, 250 ꢁ 4.6 mm). All profiles were generated by
detection of UV absorbance at 260 nm using a linear gradient solvent system:
1ꢀ10% 2-propanol in hexanes over 30 min at a flow rate of 1 mL/min.
Ferrosalen (ꢀ)-2. A solution of enantiopure (ꢀ)-11 (213 mg,
0.755 mmol) and 1,2-diaminoethane (22.7 mg, 0.378 mmol) in dry
toluene (5 mL) was stirred under a nitrogen atmosphere at room
temperature overnight. The solvent was removed under reduced
pressure. Pure product (ꢀ)-2 was given as a red foam (222 mg, 0.376
’ EXPERIMENTAL SECTION
General Considerations. All reactions were performed in oven-
dried glassware under a nitrogen atmosphere using standard Schlenk
techniques. Reagents and solvents available from commercial sources were
used as received unless otherwise noted. THF was distilled from Na/
benzophenone ketyl. MeOH, CH2Cl2, and toluene were distilled over CaH2.
Thin-layer chromatography (TLC) was performed using plates with silica
gel 60F-254 over glass support, 0.25 μm thickness. Flash column chroma-
tography was performed using silica gel with a particle size of 32ꢀ63 μm.
Scheme 2. Synthesis of Ligands 3ꢀ8
mmol, 100%): Rf = 0.1 (hexanes/CH2Cl2/Et3N 1/1/0.05); [R]21
=
D
ꢀ308.2° (c = 0.0036, CH2Cl2); 1H NMR (CDCl3) δ 9.54 (br s, 2H),
6.48 (s, 1H), 6.45 (s, 1H), 4.67 (br s, 2H), 4.31 (t, J = 2.4 Hz, 2H), 4.23
(br s, 2H), 4.12 (s, 10H), 3.34ꢀ3.10 (m, 4H), 2.94ꢀ2.82 (m, 2H),
2.39ꢀ2.02 (m, 6H); 13C NMR (CDCl3) δ 193.0, 149.8, 101.8, 91.6,
78.7, 69.5, 69.2, 68.8, 63.8, 50.0, 28.5, 23.6; HRMS (FAB) m/z calcd for
C32H32Fe2N2O2 [M]þ 588.1163, found 588.1160.
Ferrosalen (þ)-3. Following the procedure for the preparation of
(ꢀ)-2, (þ)-11 (176 mg, 0.624 mmol) and (þ)-13 (66.3 mg, 0.312
mmol) in MeOH (6 mL) were stirred at room temperature overnight.
The product was purified with flash column chromatography (SiO2,
hexanes/Et2O/MeOH 1/1/0.03), and (þ)-3 was obtained as a red foam
(168 mg, 0.227 mmol, 73%): Rf = 0.25 (SiO2, hexanes/Et2O/MeOH 1/
1/0.03); [R]21D = þ105.6° (c = 0.011, CH2Cl2); 1H NMR (CDCl3) δ
10.50 (br s, 2H), 7.20ꢀ7.10 (m, 6H), 7.02ꢀ6.92 (m, 4H), 6.71 (s, 1H),
6.68 (s, 1H), 4.74 (br s, 2H), 4.36 (t, J = 2.4 Hz, 2H), 4.28 (br s, 2H),
4.21 (s, 10H), 4.15 (s, 1H), 4.14 (s, 1H), 3.10ꢀ2.98 (m, 2H), 2.47ꢀ2.16
(m, 6H); 13C NMR (CDCl3) δ 193.4, 148.7, 138.4, 128.5, 127.7, 127.4,
Scheme 3. Synthesis of Ligands 9 and 10
2612
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616

Organometallics
ARTICLE
102.7, 91.9, 78.9, 69.8, 69.6, 69.4, 69.0, 63.9, 28.8, 23.6; HRMS (ESI) m/z
calcd for C44H40Fe2N2O2 [M þ H]þ 741.1861, found 741.1840.
Table 1. Crystal Data and Data Collection and Structure
Refinement Details for 12.
Ferrosalen (ꢀ)-4. Following the procedure for the preparation of
(ꢀ)-2, (ꢀ)-11 (359 mg, 1.27 mmol) and (þ)-13 (108 mg, 0.508 mmol)
in MeOH (15 mL) were stirred at room temperature overnight. The
product was purified with flash column chromatography (SiO2, hexanes/
Et2O/MeOH 1/1/0.03), and (ꢀ)-4 was obtained as a red foam (300 mg,
0.405 mmol, 80%): Rf = 0.25 (SiO2, hexanes/Et2O/MeOH 1/1/0.03);
[R]21D = ꢀ541.3° (c = 0.009, CH2Cl2); 1H NMR (CDCl3) δ 10.32 (br s,
2H), 7.22ꢀ6.97 (m, 10H), 6.58 (s, 1H), 6.55 (s, 1H), 4.71 (br s, 2H), 4.33
(t, J= 2.4 Hz, 2H), 4.21 (br s, 2H), 4.14 (s, 1H), 4.13 (s, 1H), 4.09 (s, 10H),
2.85ꢀ2.72 (m, 2H), 2.26ꢀ2.09 (m, 4H), 1.92ꢀ1.79 (m, 2H); 13C NMR
(CDCl3) δ 193.1, 148.3, 138.1, 128.4, 127.6, 127.0, 102.5, 91.7, 78.8, 70.7,
69.6, 69.5, 69.3, 68.7, 63.7, 28.3, 23.4; HRMS (ESI) m/z calcd for
C44H40Fe2N2O2 [M þ H]þ 741.1846, found 741.1846.
empirical formula
Mr
C32H30CuFe2N2O2
649.83
cryst syst
trigonal
space group
a, b, c/Å
V/Å3
P3121 (No. 152)
11.314(3), 11.314(3), 17.897(4)
1984.0(8)
μ/mmꢀ1
1.913
Dcalcd/g cmꢀ3
cryst size/mm
Z
1.632
0.15 ꢁ 0.25 ꢁ 0.40
3
T/K
291
2θmax/deg
50
Ferrosalen (þ)-5. Following the procedure for the preparation of
(ꢀ)-2, (þ)-14 (107 mg, 0.382 mmol) and (þ)-13 (36.9 mg, 0.174
mmol) in THF (5 mL) were stirred at room temperature for 10 h. The
product was purified with flash column chromatography (SiO2, hex-
anes/EtOAc 2/3), and (þ)-5 was obtained as a red foam (53 mg, 0.072
mmol, 76%; recovered 54 mg of ferrocenyl aldehyde): Rf = 0.20 (SiO2,
hexanes/EtOAc 2/3); [R]21D = þ2380° (c = 0.002, CH2Cl2); 1H NMR
(CDCl3) δ 7.41 (s, 1H), 7.38 (s, 1H), 7.23ꢀ7.08 (m, 10H), 6.28 (d, J =
8.8 Hz, 2H), 6.24 (d, J = 8.8 Hz, 2H), 5.11 (br s, 2H), 4.65 (br s, 2H),
4.61 (br s, 1H), 4.60 (br s, 1H), 4.34 (t, J = 2.4 Hz, 2H), 3.98 (br s, 10H);
13C NMR (CDCl3) δ 191.7, 154.7, 136.8, 129.1, 128.6, 127.5, 126.3,
113.8, 108.0, 89.4, 78.1, 71.2, 70.9, 70.5, 66.6, 64.5; HRMS (ESI) m/z
calcd for C44H36Fe2N2O2 [M]þ 736.1470, found 736.1455.
Ferrosalen (ꢀ)-6. Following the procedure for the preparation of
(ꢀ)-2, (ꢀ)-14 (96 mg, 0.343 mmol) and (þ)-13 (33.1 mg, 0.156
mmol) in THF (5 mL) were stirred at room temperature for 10 h. The
product was purified with flash column chromatography (SiO2, hex-
anes/Et2O/MeOH 1/1/0.03), and (ꢀ)-6 was obtained as a red foam
(53 mg, 0.072 mmol, 72%; 40 mg of (ꢀ)-14 was recovered): Rf = 0.25
(SiO2, hexanes/Et2O/MeOH 1/1/0.03); [R]21D = ꢀ2635° (c = 0.003,
CH2Cl2); 1H NMR (CDCl3) δ 7.30ꢀ7.09 (m, 12H), 6.12 (d, J = 9.2 Hz,
2H), 6.07 (d, J = 8.8 Hz, 2H), 5.09 (br s, 2H), 4.62 (br s, 2H), 4.54 (br s,
1H), 4.52 (br s, 1H), 4.32 (t, J = 2.4 Hz, 2H), 3.86 (s, 10H); 13C NMR
(C6D6) δ 191.4, 154.3, 136.5, 128.8, 128.3, 127.2, 125.9, 113.4, 108.0,
89.2, 77.8, 70.8, 70.0, 66.2, 64.1; HRMS (ESI) m/z calcd for C44H36Fe2-
N2O2 [M]þ 736.1470, found 736.1463.
total, unique no. of data; Rint
no. of params/restraints
R1(I g 2σ(I)), wR2, Sa
1471, 1353; 0.067
177/0
0.0554, 0.1175, 1.08
min/max resid density/e Åꢀ3
ꢀ0.35, 0.42
2
2
a w = 1/[σ2(Fo ) þ (0.0384P)2 þ 1.9441P], where P = (Fo þ 2Fc2)/3.
7.23 (d, J = 12.0 Hz, 1H), 7.06 (d, J = 12.0 Hz, 1H), 6.20 (d, J = 9.6 Hz,
1H), 6.15 (d, J = 9.2 Hz, 1H), 6.07 (d, J = 9.2 Hz, 1H), 5.98 (d, J = 8.8 Hz,
1H), 5.04 (br s, 1H), 5.01 (br s, 1H), 4.60 (br s, 1H), 4.58 (br s, 1H),
4.28 (t, J = 2.0 Hz, 1H), 4.26 (t, J = 1.6 Hz, 1H), 3.89 (s, 5H), 3.85 (s,
5H), 3.09ꢀ2.92 (m, 2H), 2.24ꢀ1.20 (m, 8H); 13C NMR (CDCl3) δ
191.1, 154.9, 126.2, 126.1, 112.9, 112.7, 106.9, 106.6, 89.4, 77.9, 70.7,
70.5, 69.9, 69.8, 66.0, 65.9, 64.4, 64.1, 63.9, 63.7, 32.2, 32.0, 24.2, 24.1;
HRMS (ESI) m/z calcd for [M]þ 638.1314, found 638.1302.
FerrosalenꢀCu(II) Complex (ꢀ)-12. A two-necked round-bot-
tom flask was charged with (ꢀ)-2 (33.6 mg, 0.057 mmol) and the
solvent mixture EtOH/H2O (9/1, 3.3 mL). Cupric acetate (11.44 mg,
0.057 mmol) was added under positive N2 pressure. After the mixture was
stirred at room temperature for 2 h, volatile components were removed
under reduced pressure. The deep red mixture was suspended in EtOH
(2 mL) and poured onto a pad of Celite. The solid on the Celite was further
washed with cold EtOH (1 mL ꢁ 2). Then, to the filter cake was added
CH2Cl2 (3 mL). The red solid was dissolved and was filtered into a clean
round-bottom flask. The Celite was further washed with CH2Cl2 (3 mL ꢁ
2). The combined red filtrate was evaporated under reduced pressure, giving
Ferrosalen (þ)-7. Following the procedure for the preparation of
(ꢀ)-2, (þ)-14 (275 mg, 0.983 mmol) and (ꢀ)-15 (56 mg, 0.492 mmol)
in MeOH (10 mL) were stirred at room temperature overnight. The
product was purified with flash column chromatography (SiO2, hexanes/
Et2O/MeOH/Et3N 10/10/1/1), and (þ)-7 was obtained as a red foam
compound (ꢀ)-12 as a red crystalline solid (28.0 mg, 75%): [R]22
=
D
ꢀ1564.7° (c = 0.002, CH2Cl2); HRMS (ESI) m/z calcd for C32H30CuFe2-
N2O2 [M]þ 649.0302, found 649.0275. This compound is paramagnetic
and was not characterized with NMR. The structure of this complex was
further confirmed with single-crystal X-ray diffraction analysis. A crystal
suitable for the analysis was grown by slowly diffusing pentane into a solution
of (ꢀ)-12 in CH2Cl2 at room temperature. Crystal data collection and
processing parameters are given in Table 1. All calculations were performed
using the SHELXL-97 program suite15 under the GUI WinGX.16 The
structures were solved by direct methods and successive interpretation of the
difference Fourier maps, followed by full-matrix least-squares refinement. All
non-hydrogen atoms were refined anisotropically. The contribution of the
hydrogen atoms, in their calculated positions, was included in the refinement
using a riding model. Upon convergence, the final Fourier difference map of
the X-ray structures showed no significant peaks. All details of the structure
solution and refinements are given in the Supporting Information (CIF
data). As is evident in a packing diagram supplied as Supporting Information,
the molecules are arranged so that the cyclopentadiene ligands are involved in
πꢀπ stacking with opposite sides of the salen moiety. These packing
interactions may be responsible for the slight twist away from planarity of the
salen ligand. Full listings of atomic coordinates, bond lengths and angles, and
displacement parameters for all the structures have been deposited at the
(252 mg, 0.394 mmol, 80%): Rf = 0.20ꢀ0.25 (SiO2, hexanes/Et2O/
1
MeOH/Et3N 10/10/1/1); [R]21 = þ5605° (c = 0.005, CH2Cl2); H
D
NMR (CDCl3) δ 7.25 (d, J = 11.2 Hz, 1H), 7.09 (d, J = 12.0 Hz, 1H), 6.22
(d, J = 9.2 Hz, 1H), 6.18 (d, J = 9.2 Hz, 1H), 6.09 (d, J = 9.2 Hz, 1H), 6.01
(d, J = 9.2 Hz, 1H), 5.07 (br s, 1H), 5.04 (br s, 1H), 4.63 (br s, 1H), 4.62 (br
s, 1H), 4.32 (t, J= 2.4 Hz, 1H), 4.30 (t, J= 2.4 Hz, 1H), 3.92 (s, 5H), 3.90 (s,
5H), 3.14ꢀ2.94 (m, 2H), 2.31ꢀ2.10 (m, 2H), 1.96ꢀ1.76 (m, 2H),
1.66ꢀ1.28 (m, 4H); 13C NMR (CDCl3) δ 191.5, 191.4, 155.2, 126.5,
126.4, 113.3, 113.1, 107.3, 107.0, 89.7, 89.5, 78.3, 71.1, 70.9, 70.3, 70.2, 66.4,
66.2, 64.9, 64.6, 64.3, 64.1, 32.6, 32.3, 24.7, 24.5; HRMS (ESI) m/z calcd for
C36H34Fe2N2O2 [M]þ 638.1314, found 638.1308.
Ferrosalen (ꢀ)-8. Following the procedure for the preparation of
(ꢀ)-2, (ꢀ)-14 (404 mg, 1.443 mmol) and (ꢀ)-15 (82.4 mg, 0.722
mmol) in MeOH (15 mL) were stirred at room temperature overnight.
The product was purified with flash column chromatography (SiO2,
hexanes/Et2O/MeOH 1/1/0.03), and (ꢀ)-8 was obtained as a red foam
(302 mg, 0.473 mmol, 65%): Rf = 0.25 (SiO2, hexanes/Et2O/MeOH 1/
1/0.03); [R]21D = ꢀ3861° (c = 0.007, CH2Cl2); 1H NMR (CDCl3) δ
2613
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616

Organometallics
ARTICLE
Cambridge Crystallographic Data Centre (deposition number: CCDC
816340).
being warmed to ꢀ20 °C gradually. Saturated ammonium chloride
(50 mL) was then added. The mixture was diluted with water (50 mL)
and extracted with ether (50 mL ꢁ 3). The ether phase was washed with
brine (100 mL), dried over anhydrous Na2SO4, and concentrated to
dryness under reduced pressure at room temperature. The two diaster-
eoisomers 21xa and 21ya were not very stable; they lose their chiral
auxiliary slowly even at room temperature. A quick separation with flash
column chromatography (SiO2, hexanes/Et2O 2/1) gave pure 21xa, as
indicated by TLC (Rf = 0.55, SiO2, hexanes/Et2O 1/1). However, 21ya
was found to be contaminated with (()-19a. Because 21ya and (()-19a
have similar Rf values (Rf = 0.45, SiO2, hexanes/Et2O 1/1), attempts to
separate them were not successful. The pure 21xa was dissolved in dry
toluene (30 mL), and the solutions were heated to reflux for 12 h. After
the solution was cooled to room temperature, volatiles were removed.
The residue was purified with flash chromatography (SiO2, hexanes/
Et2O 2/1). Enantiopure (þ)-19a was obtained as a red solid (1.11 g,
91%): Rf = 0.45 (SiO2, hexanes/Et2O 1/1); mp 110 °C; [R]23D = þ532°
(c = 0.018, CH2Cl2); 1H NMR (C6D6) δ 4.32 (br s, 1H), 3.63 (t, J = 2.4
Hz, 1H), 3.56 (br s, 1H), 2.30ꢀ2.22 (m, 1H), 2.16ꢀ2.08 (m, 1H),
2.03ꢀ1.76 (m, 4H), 1.57 (s, 15H); 13C NMR (C6D6) δ 201.2, 90.6,
80.6, 77.2, 75.5, 73.7, 69.8, 39.5, 23.9, 21.7, 10.3; HRMS (ESI) m/z calcd
for C19H24FeO [M]þ 324.1182, found 324.1173. The impure 21ya was
also heated in toluene to give (ꢀ)-19a, which was contaminated with
(þ)-19a (totally 1.20 g). The chiral auxiliary 20 was recovered without
losing any optical purity. The combined yield of 20 from 21xa and 21ya
was 89% (2.50 g).
Ferrocenyl Ketocarboxylic Acid 17a. An oven-dried two-
necked round-bottom flask was flushed with argon. AlCl3 (3.195 g,
23.96 mmol) and CH2Cl2 (30 mL) were added. Compound 16a11 (5.113 g,
19.97 mmol) in CH2Cl2 (50 mL) was then added dropwise via a cannula.
The solution turned dark brown. After addition, succinic anhydride (2.398 g,
23.96 mmol) was added under positive argon pressure. The mixture was
stirred at room temperature overnight. The reaction flask was cooled with an
ice bath. Ice water (80 mL) was added to the mixture slowly over about 5
min. The contents were transferred to a separation funnel. The organic and
aqueous phases were separated. The organic phase was washed with water
(50 mL ꢁ 3), dried over anhydrous Na2SO4, and filtered. Solvents were
removed under reduced pressure. The residue was purified with flash
column chromatography (SiO2, hexanes/Et2O/CH2Cl2 2/1/1), giving
17a as a red solid (5.23 g, 74%): Rf = 0.20 (SiO2, hexanes/Et2O/CH2Cl2
2/1/1); mp 135 °C dec; 1H NMR (CDCl3) δ 4.24 (br s, 1H), 3.99 (br s,
2H), 2.90 (br s, 2H), 2.61 (br s, 2H), 1.76 (s, 15H); 13C NMR (CDCl3) δ
202.7, 178.6, 81.5, 80.0, 76.5, 71.7, 35.4, 29.5, 10.6; HRMS (ESI) m/z calcd
for C19H24FeO3 [M]þ 356.1080, found 356.1071.
Ferrocenyl Carboxylic Acid 18a. In a two-necked round-bottom
flask containing 17a (3.80 g, 10.67 mmol) and toluene (100 mL) was
added Zn dust (20.90 g, 319.6 mmol) and HgCl2 (1.94 g, 7.143 mmol)
sequentially under positive argon pressure. The mixture was stirred
vigorously while H2O (100 mL) and then HCl (12.1 M, 100 mL) were
added via syringe. After addition, the mixture was heated to reflux for
about 3 h. TLC indicated that 17a was completely consumed. The
reaction mixture was cooled to room temperature. Some solids were
formed, which were removed by filtration. The mother liquor was
transferred into a separation funnel. The aqueous phase was removed.
The organic phase was washed with brine (80 mL ꢁ 2), dried over
anhydrous Na2SO4, and filtered. Solvents were evaporated under
reduced pressure, giving pure 18a as a red solid (3.47 g, 95%): Rf =
0.45 (short SiO2 column, hexanes/Et2O/CH2Cl2 2/1/1); mp
Ferrocenyl Ketoformaldehyde (þ)-22a. In a two-necked
round-bottom-flask was charged (þ)-19a (124.0 mg, 0.380 mmol)
and NaH (153.0 mg, 3.82 mmol) under nitrogen. THF (15 mL) and
ethyl formate (0.308 mL, 3.82 mmol) were added via syringe sequen-
tially. The mixture was heated to reflux for 3 h. TLC indicated that the
reaction was complete. After the mixture was cooled to room tempera-
ture, water (30 mL) was added, and the contents were transferred into a
separation funnel. The mixture was extracted with ether (15 mL ꢁ 3).
The combined ether extracts were washed with brine (30 mL), dried
over anhydrous Na2SO4, and concentrated under reduced pressure.
Purification with flash column chromatography (SiO2, hexanes/Et2O 4/
1) gave (þ)-22a as a red solid (125.0 mg, 93%): Rf = 0.60 (SiO2,
1
61ꢀ64 °C; H NMR (CDCl3) δ 3.69 (br s, 2H), 3.59 (br s, 2H),
2.40 (t, J = 7.2 Hz, 2H), 2.34 (t, J = 7.2 Hz, 2H), 1.95 (s, 15H),
1.87ꢀ1.80 (m, 2H); 13C NMR (CDCl3) δ 180.2, 86.7, 79.8, 71.6, 70.8,
33.5, 27.0, 26.5, 10.9; HRMS (ESI) m/z calcd for C19H26FeO2 [M]þ
342.1288, found 342.1276.
hexanes/Et2O 1/1); mp 130 °C (dec); [R]23 = þ659° (c = 0.018,
D
CH2Cl2); 1H NMR (C6D6) δ 7.21 (br s, 1H), 4.29 (m, 1H), 3.72 (t, J =
2.8 Hz, 1H), 3.58 (m, 1H), 2.33ꢀ2.23 (m, 1H), 2.12ꢀ1.92 (m, 4H),
1.54 (s, 15H); 13C NMR (C6D6) δ 195.4, 164.6, 109.2, 90.4, 81.2, 76.4,
74.2, 68.9, 24.6, 20.9, 10.3; HRMS (ESI) m/z calcd for C20H24FeO2
[M]þ 352.1131, found 352.1117.
Racemic Ferrocenyl Cyclohexanone (()-19a. A two-necked
round-bottom flask was charged with 18a (3.470 g, 10.14 mmol) and
CCl4 (100 mL), and wrapped with aluminum foil. The solution was
bubbled with argon for 10 min. After the solution was cooled to 0 °C,
trifluoroacetic anhydride (5.60 mL, 40.30 mmol) was added via a syringe.
The mixture was stirred on an ice bath and warmed to room temperature
gradually. TLC indicated that the reaction was complete in 3 h. The contents
were transferred into a separation funnel and partitioned between 10%
NaOH (120 mL) and CH2Cl2 (80 mL). The organic phase was washed with
brine (100 mL ꢁ 2), dried over anhydrous Na2SO4, and filtered. Volatiles
were removed under reduced pressure. Purification with flash column
chromatography (SiO2, hexanes/Et2O 2/1) gave (()-19a as a red solid
(2.44 g, 74%): Rf = 0.30 (SiO2, hexanes/Et2O 1/1); mp 102 °C; 1H NMR
(C6D6) δ 4.28ꢀ4.26 (m, 1H), 3.63 (t, J = 2.4 Hz, 1H), 3.58ꢀ3.56 (m, 1H),
2.28ꢀ2.20 (m, 1H), 2.17ꢀ2.09 (m, 1H), 2.04ꢀ1.77 (m, 4H), 1.56 (s,
15H); 13CNMR(C6D6) δ201.2, 90.6, 80.6, 77.1, 75.6, 73.7, 69.7, 39.5, 23.9,
21.7, 10.3; HRMS (ESI) m/z calcd for C19H24FeO [M]þ 324.1182, found
324.1172.
Ferrosalen (þ)-9. Following the procedure for the preparation
of (ꢀ)-2, (þ)-22a (122.0 mg, 0.345 mmol) and 1,2-diaminoethane
(11.5 μL, 0.172 mmol) in MeOH (5 mL) were stirred at 50 °C for 2 h.
The product was purified with flash column chromatography (SiO2,
hexanes/Et2O/MeOH 1/1/0.08), and (þ)-9 was obtained as a red solid
(101 mg, 80%): Rf = 0.35 (SiO2, hexanes/Et2O/MeOH 1/1/7.5%); mp
82 °C dec; [R]23D = þ120° (c = 0.015, CH2Cl2); 1H NMR (C6D6) δ
9.72 (br s, 2H), 6.12 (s, 1H), 6.09 (s, 1H), 4.50 (br s, 2H), 3.70 (t, J = 2.4
Hz, 2H), 3.57 (br s, 2H), 2.70ꢀ2.57 (m, 2H), 2.50ꢀ2.11 (m, 10H), 1.71
(s, 30H); 13C NMR (C6D6) δ 192.3, 148.9, 102.3, 89.9, 80.5, 79.8, 74.7,
72.6, 69.0, 49.9, 28.5, 22.0, 10.5; HRMS (ESI) m/z calcd for C42H52Fe2-
N2O2 [M]þ 728.2733, found 728.2730.
Ferrocene 16b. This compound was synthesized using a modified
literature procedure.13 To a solution of 1-bromopentaphenylcyclopen-
tadiene (132 mg, 0.25 mmol) in benzene (5 mL) was added Fe(CO)5
(59.0 mg, 0.30 mmol) under nitrogen. The mixture was heated to reflux
for 3 h. After this mixture was cooled to room temperature, a solution of
CpNa (0.263 mL of 2.0 M in THF, 0.525 mmol) was added via syringe.
The mixture was stirred at room temperature for 18 h. The resulting
orange mixture was filtered through Celite. The filtrate was collected,
Enantiopure Ferrocenyl Cyclohexanone (þ)-19a. To a
solution of (þ)-(S)-N,S-dimethyl-S-phenylsulfoximine (20; 2.80 g,
16.5 mmol) in dry THF (40 mL) at 0 °C was added a solution of n-
butyllithum in hexane (2.0 M, 8.30 mL). After it was stirred for 15 min at
this temperature, the mixture was cooled to ꢀ78 °C. The racemic (()-
19a (2.44 g, 7.53 mmol) in dry THF (60 mL) was added via cannula
dropwise over 10 min. The mixture was stirred for an additional 3 h while
2614
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616

Organometallics
ARTICLE
and solvents were removed under reduced pressure. The orange residue
was heated to 160 °C under vacuum for 3 h. After it was cooled to room
temperature, the remaining mixture was suspended in toluene and
filtered through Celite. The filtrate was collected, and solvents were
removed. Purification by recrystallization in hot toluene gave 16b as a
red crystalline solid (115 mg, 81%).
Ferrocenyl Ketocarboxylic Acid 17b. Following a procedure
similar to that for the preparation of 17a, the reaction of 16b (1.882 g,
3.325 mmol), AlCl3 (0.935 g, 7.012 mmol), and succinic anhydride
(0.332 g, 3.323 mmol) in CH2Cl2 at reflux temperature in 24 h gave 17b
as a red foam after purification with flash column chromatography (SiO2,
hexanes/Et2O 1/1; 1.65 g, 75%): Rf = 0.15 (SiO2, hexanes/Et2O 1/1);
1H NMR (CDCl3) δ 7.18ꢀ7.01 (m, 25H), 4.88 (br s, 2H), 4.50 (br s,
2H), 2.80 (t, J = 7.2 Hz, 2H), 2.39 (t, J = 7.2 Hz, 2H); 13C NMR
(CDCl3) δ 201.9, 178.3, 134.7, 132.1, 127.2, 126.6, 88.2, 83.1, 79.0, 74.8,
36.2, 27.9; HRMS (ESI) m/z calcd for C44H34FeO3 [M þ H]þ
667.1936, found 667.1948.
Ferrocenyl Carboxylic Acid 18b. Following a procedure similar
to that for the preparation of 18a, the reduction of 17b (1.65 g, 2.477
mmol) with Zn dust (4.860 g, 74.31 mmol) and HgCl2 (0.450 g, 1.657
mmol) in toluene (20 mL), H2O (20 mL), and HCl (12.1 M, 20 mL) at
reflux temperature in 24 h gave 18b as a red solid after purification with
flash column chromatography (short SiO2 column, hexanes/Et2O 2/1;
1.35 g, 84%): Rf = 0.30 (SiO2, hexanes/Et2O 1/1); mp 192 °C; 1H NMR
(CDCl3) δ 7.15ꢀ7.01 (m, 25H), 4.15 (br s, 2H), 4.12 (br s, 2H),
2.30ꢀ2.18 (m, 4H), 1.79ꢀ1.68 (m, 2H); 13C NMR (CDCl3) δ 179.1,
135.9, 132.4, 127.1, 126.1, 90.5, 87.6, 75.0, 74.1, 33.2, 26.7, 26.5; HRMS
(ESI) m/z calcd for C44H36FeO2 [M]þ 652.2065, found 652.2075. The
compound may decompose slowly at room temperature, and storing
at ꢀ20 °C is suggested.
impure 21xb was also heated in toluene to give (þ)-19b, which was
contaminated with (ꢀ)-19b (total 262 mg). The chiral auxiliary 20 was
recovered without losing any optical purity. The combined yield of 20
from 21xb and 21yb was 86% (300 mg).
Ferrocenyl Ketoaldehyde (ꢀ)-22b. A procedure similar to that
for the synthesis of (þ)-22a was followed. Compound (ꢀ)-19b 171.0
mg, 0.269 mmol), NaH (214.0 mg, 5.380 mmol), and ethyl formate
(0.434 mL, 5.380 mmol) in THF (20 mL) were heated to reflux
overnight. After the mixture was cooled to room temperature, saturated
NH4Cl (30 mL) was added. The mixture was extracted with EtOAc
(15 mL ꢁ 2). The organic phase was washed with brine (30 mL), dried
over anhydrous Na2SO4, and concentrated under reduced pressure.
Purification by flash column chromatography (short SiO2 column,
hexanes/CH2Cl2/EtOAc 40/10/1) gave (ꢀ)-22b as a red solid
(138.0 mg, 77%). The product may decompose slowly on silica gel.
Enantiopure (ꢀ)-22b: Rf = 0.25 (SiO2, hexanes/Et2O 5/1); mp 210 °C
dec; [R]22 = ꢀ197° (c = 0.009, CH2Cl2); 1H NMR (CDCl3) δ
D
7.50ꢀ7.43 (br s, 1H), 7.20ꢀ6.96 (m, 25H), 4.86 (t, J = 2.0 Hz, 1H), 4.42
(br s, 1H), 4.41 (br s, 1H), 2.68ꢀ2.58 (m, 1H), 2.44ꢀ2.24 (m, 3H); 13C
NMR (CDCl3) δ 194.7, 165.4, 134.6, 132.5, 127.4, 126.7, 111.1, 91.4,
88.3, 78.7, 78.4, 77.7, 73.2, 25.6, 21.4; HRMS (ESI) m/z calcd for
C45H34FeO2 [M]þ 662.1914, found 662.1904.
Ferrosalen (ꢀ)-10. Following the procedure for the preparation of
(ꢀ)-2, (ꢀ)-22b (40.0 mg, 0.0604 mmol) and 1,2-diaminoethane
(1.68 μL, 0.0251 mmol) in MeOH (5 mL) were stirred at 50 °C for
24 h. Purification by flash column chromatography (SiO2, hexanes/
Et2O/MeOH 1/1/0.02) gave (ꢀ)-10 as a red solid (23.0 mg, 68%): Rf =
0.10 (SiO2, hexanes/Et2O 1/1); mp 124ꢀ127 °C; [R]22D = ꢀ69° (c =
0.0225, CH2Cl2); 1H NMR (CDCl3) δ 9.38 (br s, 2H), 7.14ꢀ6.96 (m,
50H), 6.46 (s, 1H), 6.43 (s, 1H), 4.75 (br s, 2H), 4.24 (br s, 4H),
3.32ꢀ3.20 (br s, 2H), 3.14ꢀ3.00 (br s, 2H), 2.58ꢀ2.06 (m, 8H); 13C
NMR (CDCl3) δ 192.0, 149.1, 135.2, 132.7, 127.2, 126.3, 103.9, 91.3,
87.9, 82.0, 77.0, 76.6, 72.7, 50.4, 29.2, 22.2; HRMS (ESI) m/z calcd for
C92H72Fe2N2O2 [M]þ 1348.4293, found 1348.4292; calcd for [M þ
H]þ 1349.4365, found 1349.4360.
Racemic Ferrocenyl Cyclohexanone (()-19b. Following a
procedure similar to that for the preparation of (()-19a, cyclization of
18b (424.0 mg, 0.650 mmol) to give (()-19b was achieved with
trifluoroacetic anhydride (1.0 mL, 7.195 mmol) in CCl4 (15 mL) at
50 °C overnight. Purification with flash column chromatography (SiO2,
hexanes/CH2Cl2/Et2O 20/20/1) gave the product as a red solid (375.0
mg, 91%): Rf = 0.30 (hexanes/CH2Cl2/Et2O 20/20/1); mp 220 °C dec;
1H NMR (CDCl3) δ 7.16ꢀ6.98 (m, 25H), 4.84ꢀ4.82 (m, 1H),
4.45ꢀ4.43 (m, 1H), 4.37 (t, J = 2.4 Hz, 1H), 2.65ꢀ2.55 (m, 1H),
2.44ꢀ2.28 (m, 3H), 2.02ꢀ1.94 (m, 1H), 1.77ꢀ1.64 (m, 1H); 13C NMR
(CDCl3) δ 203.9, 134.5, 132.2, 127.2, 126.5, 94.4, 87.7, 78.4, 77.8, 77.2,
72.8, 39.5, 24.9, 21.8; HRMS (ESI) m/z calcd for C44H34FeO [M]þ
634.1965, found 634.1959.
Enantiopure Ferrocenyl Cyclohexanone (ꢀ)-19b. Following
a procedure similar to that for the resolution of (()-19a, (()-19b
(437.0 mg, 0.688 mmol) was first converted to 21xb and 21yb using
(þ)-(S)-20 (349.0 mg, 2.065 mmol) and n-butyllithum in hexane (2.0
M, 1.032 mL) in THF. Because the two diastereoisomers 21xb and 21yb
slowly lose the chiral auxiliary even at room temperature, they were
quickly separated with flash column chromatography (short SiO2
column, hexanes/CH2Cl2/EtOAc 20/10/1). TLC analysis indicated
that 21xb was still contaminated with (()-19b. Because their Rf values
were very close (Rf = 0.35, SiO2, hexanes/Et2O 2/1), attempts to
separate them were not successful. However, the other diastereoisomer
21yb, which had an Rf value of 0.20 (SiO2, hexanes/Et2O 2/1), was
obtained in pure form. The solution of 21yb in dry toluene (10 mL) was
then heated to reflux overnight. Enantiopure (ꢀ)-19b was obtained as a
red solid (171 mg, 78%): Rf = 0.35 (SiO2, hexanes/CH2Cl2/EtOAc 20/
10/1); mp 220 °C dec; [R]23D = ꢀ311° (c = 0.0095, CH2Cl2); 1H NMR
(CDCl3) δ 7.17ꢀ6.96 (m, 25H), 4.83 (br s, 1H), 4.44 (br s, 1H), 4.38
(br s, 1H), 2.66ꢀ2.55 (m, 1H), 2.45ꢀ2.28 (m, 3H), 2.02ꢀ1.93 (m,
1H), 1.79ꢀ1.64 (m, 1H); 13C NMR (CDCl3) δ 204.0, 134.5, 132.2,
127.2, 126.5, 94.4, 87.7, 78.4, 77.8, 77.2, 72.8, 39.5, 24.9, 21.8; HRMS
(ESI) m/z calcd for C44H34FeO [M]þ 634.1965, found 634.1956. The
Enantioselective Carbonyl-Ene Reaction Catalyzed with
Ferrosalen-Co(III) Complexes.17. Ligand (ꢀ)-8 is used as an
example. In a round-bottom flask containing (ꢀ)-8 (190 mg, 0.298
mmol) and MeOH (10 mL) was added Co(OAc)2 4H2O (74.2 mg,
3
0.298 mmol) in MeOH (5 mL) via a cannula. The mixture was stirred at
room temperature for 1 h. The solvent was removed under reduced
pressure on a rotary evaporator. The flask, which contained the residue,
was then wrapped with an aluminum foil. CH2Cl2 (15 mL) was added
via syringe, which was followed by addition of AgSbF6 (205 mg, 0.596
mmol). The mixture was stirred at room temperature overnight. The
resulting black suspension was poured onto a pad of Celite, which was
washed with CH2Cl2. The filtrate was discarded. The Celite pad was
then washed with acetone. The filtrate was concentrated to dryness
under reduced pressure to give the (ꢀ)-8ꢀCo(III) complex. The com-
pound was used directly as a catalyst for the carbonyl-ene reaction
without further purification. Ethyl glyoxylate (50% in toluene; 250.9 mg,
1.23 mmol) was heated to reflux under nitrogen for 1 h to crack its dimer.
After it was cooled to room temperature, the solution was added to a
round-bottom flask containing (ꢀ)-8ꢀCo(III) (19.0 mg, 0.02 mmol) in
dry toluene (3 mL). The mixture was stirred at room temperature for 10
min. R-Methylstyrene (48.2 mg, 0.41 mmol) was then added via syringe
in one portion. The reaction was allowed to proceed at room tempera-
ture, and the progress was monitored with GC-MS. After 16 h, the
mixture was passed through a pad of Celite, which was washed with
CH2Cl2 (3 mL ꢁ 3). Volatiles were removed under reduced pressure.
The residue was purified with flash column chromatography (SiO2,
hexanes/Et2O 4/1). The product 2317 was obtained as a colorless oil
(70.0 mg, 78%). The ee was determined with chiral HPLC using the con-
ditions described in General Considerations. The enantiomers S-23 and
2615
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616

Organometallics
ARTICLE
R-23 were eluted at 17.0 and 21.0 min, respectively. The ee was 29%,
with R being the major enantiomer. In addition to ligand (ꢀ)-8, all other
ligands, including (ꢀ)-1, (ꢀ)-2, (þ)-3, (ꢀ)-4, (þ)-5, (ꢀ)-6, (þ)-7,
(þ)-9, and (ꢀ)-10, were also tested for the reaction. The yields ranged
from 20% to 99%. The ee's ranged from 0% to 10%.
MTU Chemistry Department and assistance from Mr. Jerry L.
Lutz (NMR), Mr. Shane Crist (computation), and Mr. Dean W.
Seppala (electronics) are gratefully acknowledged.
Enantioselective Strecker Reaction Catalyzed with Ferro-
salen-Al(III) Complexes.18. Ligand (ꢀ)-1 is used as an example. In a
round-bottom flask containing ligand (ꢀ)-1 (18.0 mg, 0.031 mmol) and dry
CH2Cl2 (5 mL) was added Et2AlCl (1.0 M solution in hexanes, 27.8 μL,
0.028 mmol) via syringe. The mixture was stirred at room temperature for 2 h
under nitrogen. (E)-N-Butylideneprop-2-en-1-amine (34.5 mg, 0.31 mmol)
was added via syringe. After the mixture was cooled to ꢀ78 °C, the solution of
TMSCN (62 μL, 0.456 mmol) in CH2Cl2 (2 mL) was added via a cannula
dropwise. The reaction mixture was warmed to room temperature gradually
over 12 h. Pyridine (2 mL) was added, which was followed by benzoyl
chloride (0.5 mL). The mixture was stirred for 1 h. Solvent was removed
under reduced pressure. The residue was purified by flash column chroma-
tography (SiO2, hexanes/Et2O 10/1 to 5/1) to give pure product 24 as a
colorless oil (77.9 mg, 100%).18 The ee was determined with chiral HPLC
using the conditions described in General Considerations. The enantiomers
(ꢀ)-24 and (þ)-24 were eluted at 19.1 and 20.0 min, respectively. The ee
was 20%, with (þ)-24 being the major enantiomer. In addition to ligand
(ꢀ)-1, all other ligands, including (ꢀ)-2, (þ)-3, (ꢀ)-4, (þ)-5, (ꢀ)-6, (þ)-
7, (ꢀ)-8, (þ)-9, and (ꢀ)-10, were also tested for the reaction. The yields
were all quantitative. The ee's ranged from 0% to 18%.
’ REFERENCES
(1) (a) Irie, R.; Noda, K.; Ito, Y.; Katsuki, T. Tetrahedron Lett. 1991,
32, 1055–1058. (b) Hosoya, N.; Hatayama, A.; Irie, R.; Sasaki, H.;
Katsuki, T. Tetrahedron 1994, 50, 4311–4322. (c) Irie, R.; Noda, K.; Ito,
Y.; Matsumoto, N.; Katsuki, T. Tetrahedron Lett. 1990, 31, 7345–7348.
(d) Sasaki, H.; Irie, R.; Hamada, T.; Suzuki, K.; Katsuki, T. Tetrahedron
1994, 50, 11827–11838.
(2) Ballistreri, F. P.; Patti, A.; Pedotti, S.; Tomaselli, G. A.; Toscano,
R. M. Tetrahedron: Asymmetry 2007, 18, 2377–2380.
(3) Wolfle, H.; Kopacka, H.; Wurst, K.; Ongania, K. H.; Gortz, H. H.;
Preishuber-Pflugl, P.; Bildstein, B. J. Organomet. Chem. 2006, 691,
1197–1215.
(4) (a) Niemeyer, J.; Kehr, G.; Frohlich, R.; Erker, G. Eur. J. Inorg.
Chem. 2010, 680–684. (b) Niemeyer, J.; Cloppenburg, J.; Frohlich, R.;
Kehr, G.; Erker, G. J. Organomet. Chem. 2010, 695, 1801–1812.
(5) (a) Thimmaiah, M.; Luck, R. L.; Fang, S. Open Org. Chem. J.
2008, 2, 1–9. (b) Thimmaiah, M.; Luck, R. L.; Fang, S. J. Organomet.
Chem. 2007, 692, 1956–1962. (c) Thimmaiah, M.; Zhang, X.; Fang, S.
Tetrahedron Lett. 2008, 49, 5605–5607. (d) Thimmaiah, M.; Fang, S.
Tetrahedron 2007, 63, 6879–6886.
(6) Zhang, X.; Luck, R. L.; Fang, S. J. Organomet. Chem. 2010,
Enantioselective Silylcyanation of Aldehyde.4b. Ligand (þ)-
3 is used as an example. In a round-bottom flask under nitrogen was
charged (þ)-3 (15.2 mg, 0.0205 mmol) and CH2Cl2 (1 mL). Et2AlCl (20.5
uL of 1.0 M solution in hexanes, 0.0205 mmol) was added via syringe. The
mixture was stirred at room temperature for 5 h. Oct3PO (23.8 mg, 0.0616
mmol) in CH2Cl2 (1 mL) was then added via cannula. After the mixture was
cooled to ꢀ20 °C, freshly distilled benzaldehyde (43.6 mg, 0.41 mmol) and
trimethylsilyl cyanide (136 μL, 1.025 mmol) were added via syringe sequen-
tially. The reaction was allowed to proceed at ꢀ20 °C, monitored with GC-
MS, and and found complete in 24 h. Volatiles were removed under reduced
pressure. The residue was suspended inetherandpassedthrougha1in. padof
silica gel to remove the catalyst. The filtrate was concentrated to dryness.
Purification with flash column chromatography (SiO2, hexanes/Et2O 10/1)
gave product 254b as a colorless liquid (76.0 mg, 89%). The ee was determined
with chiral HPLC using the conditions described in General Considerations.
The enantiomers S-25 and R-25 were eluted at 4.9 and 6.0 min, respectively.
The ee was 26%, with R being the major enantiomer. In addition to ligand
(þ)-3, all other ligands, including (ꢀ)-1, (ꢀ)-2, (ꢀ)-4, (þ)-5, (ꢀ)-6, (þ)-
7, (ꢀ)-8, (þ)-9, and (ꢀ)-10, were also tested for the reaction. The yields
ranged from 63% to 99%. The ee's ranged from 0% to 26%.
doi:10.1016/j.jorganchem.2010.1010.1064.
(7) Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am.
Chem. Soc. 1990, 112, 2801–2803.
(8) Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki, M. J. Am.
Chem. Soc. 2007, 129, 4900–4901.
(9) Katsuki, T. Chem. Soc. Rev. 2004, 33, 437–444.
(10) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
(11) Raabe, E.; Koelle, U. J. Organomet. Chem. 1985, 279, C29–C32.
(12) Kuehne, M. E.; Dai, W. N.; Li, Y. L. J. Org. Chem. 2001,
66, 1560–1566.
(13) Butler, D. C. D.; Richards, C. J. Organometallics 2002,
21, 5433–5436.
(14) Kurono, N.; Arai, K.; Uemura, M.; Ohkuma, T. Angew. Chem.,
Int. Ed. 2008, 47, 6643–6646.
(15) Sheldrick, G. M. SHELX-97, Programs for Crystal Structure
Analysis (Release 97-2); University of Gottingen, Gottingen, Germany,
1998.
(16) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837–838.
(17) Hutson, G. E.; Dave, A. H.; Rawal, V. H. Org. Lett. 2007,
9, 3869–3872.
(18) Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998,
120, 5315–5316.
’ ASSOCIATED CONTENT
Supporting Information. Figures giving 1H and 13C
S
b
NMR spectra and MS of all new compounds, chiral HPLC profiles,
and a crystal packing diagram and a CIF file giving X-ray crystal-
lographic data for the structure determination of 12. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Tel: þ001 (906) 487-2023. Fax: þ001 (906) 487-2061. E-mail:
shifang@mtu.edu.
’ ACKNOWLEDGMENT
Financial support from the US NSF (No. CHE-0647129),
Michigan Universities Commercialization Initiative, and the
2616
dx.doi.org/10.1021/om2002206 |Organometallics 2011, 30, 2609–2616