Iron- and cobalt-catalyzed asymmetric hydrosilylation of ketones and enones with bis(oxazolinylphenyl)amine ligands

Article abstract of DOI:10.1002/chem.200903118

Chiral bis(oxazolinylphenyl)amines proved to be efficient auxiliary ligands for iron and cobalt catalysts with high activity for asymmetric hydrosilylation of ketones and asymmetric conjugate hydrosilylation of enones.

Full text of DOI:10.1002/chem.200903118

DOI: 10.1002/chem.200903118
Iron- and Cobalt-Catalyzed Asymmetric Hydrosilylation of Ketones and
Enones with Bis(oxazolinylphenyl)amine Ligands
Tomohiko Inagaki, Le Thanh Phong, Akihiro Furuta, Jun-ichi Ito, and
Hisao Nishiyama*[a]
Dedicated to Professor Kenji Itoh on the occasion of his 70th birthday
Abstract: Chiral bis(oxazolinylphenyl)amines proved to be efficient auxiliary li-
gands for iron and cobalt catalysts with high activity for asymmetric hydrosilyla-
tion of ketones and asymmetric conjugate hydrosilylation of enones.
Keywords: asymmetric catalysis
·
·
bisoxazoline ligands
·
cobalt
hydrosilylation · iron
Introduction
jugate reduction of enones with a Co–Bopa catalyst and hy-
drosilane.
The creation of new chiral ligands that can control the chiral
environment around active metal centers is of importance
for asymmetric catalysis in organic synthesis. Much attention
has focused on multi-nitrogen ligands such as tridentate
N,N,N-type ligands bearing a chiral oxazoline skeleton to
attain asymmetric catalysis.[1] Among them, tridentate
N,N,N-bis(oxazolinylphenyl)amine (Bopa) ligands 1 have
been used in asymmetric catalytic reactions such as Nozaki–
Hiyama allylation by Guiry and co-workers,[2] and in the
Henry reaction, Friedel–Crafts reaction, and nitroalkane Mi-
chael addition by Du, Xu et al.[3] Bopa can efficiently act as
a chiral tridentate bisoxazoline/amine or bisoxazoline/amide
ligand with C2 symmetry in combination with Zn, Cu, and
Cr atoms. We are interested in the potential of Bopa as a
chiral ligand, and we have reported preliminary data on
asymmetric Fe-catalyzed hydrosilylation of ketones with
Beller et al. reported asymmetric hydrosilylation of ke-
tones with Fe catalysts in combination with several chiral
phosphine ligands, and achieved 99% ee for hindered aro-
matic ketones.[5] Recently, Gade et al. applied new chiral
bis(pyridylimino)isoindoles and their Fe complexes to asym-
metric hydrosilylation to attain high enantioselectivity.[6]
Bopa ligands.[4] Here we present the scope and limitations
of asymmetric hydrosilylation of ketones with chiral Bopa li-
gands in combination with first-row transition metals such
as Fe and Co. In addition, we have performed efficient con-
Chirik et al. also found that iron bisACHTGNUTERNNU(G imino)pyridine and bis-
(oxazolinyl)pyridine catalysts exhibit high catalytic activity
for hydrosilylation of ketones.[7] The use of ubiquitous iron
among the first-row transition metals is very important in
terms of environmentally benign processes that avoid pre-
cious metals. With regard to Fe-catalyzed reduction of ke-
tones, new asymmetric catalyst systems for transfer hydroge-
nation and hydrogenation of ketones were reported recently
by Beller et al., Morris et al., and Casey et al.[8–11]
[a] T. Inagaki, L. T. Phong, A. Furuta, Assist. Prof. Dr. J.-i. Ito,
Prof. Dr. H. Nishiyama
Department of Applied Chemistry
Graduate School of Engineering, Nagoya University
Chikusa, Nagoya, 464–8603 (Japan)
Fax : (+81)52-789-3209
We found that FeACTHNUTRGNEUNG(OAc)2-catalyzed hydrosilylation of ke-
tones with several hydrosilanes can be readily promoted in
the presence of N,N,N’,N’-tetramethylethylenediamine
(TMEDA, Scheme 1).[4a] When we adopted Bopa-tb (1b, 7
mol%) as a chiral ligand in place of TMEDA, we observed
E-mail: hnishi@apchem.nagoya-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200903118.
3090
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 3090 – 3096

FULL PAPER
Table 1. Asymmetric hydrosilylation of methyl-4-phenylphenyl ketone
(2a) with Fe
N
(OAc)2/Bopa catalysts.[a]
ACHTUNGTRENNUNG
Entry
Ligand
Yield [%]
ee [%]
1
2
3
Fe
Fe
Fe
Fe
Fe
Fe
Co
Co
Co
Co
Co
Co
Co
U
1a
1b
1c
1c
1c
1d
none
1a
1b
1c
1d
1d
1d
99
90
99
99
99
92
19
99
99
99
99
10
42
61
68[b]
72
73
72
20
–
70
69
54
94
94
67
4[c]
5[d]
6
7
8
9
10
11
12[e]
13[f]
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
E
AHCTUNGTRENNUNG
Scheme 1. Previously reported iron-catalyzed hydrosilylation reactions.
AHCTUNGTRENNUNG
[a] For Fe cat.: Ketone 2a (1.0 mmol), Fe
(7.0 mol%), (EtO)2MeSiH (2.0 mmol), THF (3.0 mL), 658C, 24 h,
workup with H3O+. For Co cat.: Ketone 2a (1.0 mmol), Co
(OAc)2
ACHTUNGRTEN(NUGN OAc)2 (5.0 mol%), Bopa
the highest enantioselectivity of 79%. We used this as a
starting point to study the scope and limitations of iron cata-
lysts in combination with chiral Bopa ligands.
ACHTUNGTRENNUNG
(5.0 mol%), Bopa (6.0 mol%), (EtO)2MeSiH (2.0 mmol), THF (3.0 mL),
658C, 24 h, workup with KF, tetra-n-butylammonium fluoride (TBAF).
All products have R absolute configuration. [b] 48 h. Previously, 75%
yield and 79% ee at 658C and 48 h were reported.[4a] [c] Fe
ACHTUNGTRENNUNG
(2.0 mol%), Bopa-dpm (3.0 mol%). [d] Fe
dpm (0.6 mol%). [e] In place of Co
ACHTUNGTRENNUNG
Results and Discussion
N
ACHTUNGTRENNUNG
used. [f] In place of (EtO)2MeSiH, NaBH4 (2.0 mmol) was used.
Asymmetric hydrosilylation of ketones with Fe and Co
Bopa catalysts: We previously reported asymmetric hydrosi-
lylation of methyl 4-phenylphenyl ketone (2a) catalyzed by
iron(II) acetate (5 mol%) and Bopa-ip (1a) or Bopa-tb (1b)
(7 mol%) with (EtO)2MeSiH (2.0 equiv) in THF at 658C
for about 24 h with 75–85% yield and 57–79% ee.[4] As
bulky substituents on the oxazoline rings resulted in higher
enantioselectivity, we examined the substrate scope with
Bopa-tb (1b), new ligand Bopa-dpm (1c), and Bopa-ph (1d;
Scheme 2 and Table 1, entries 1–6). The catalyst was pre-
57%. Other hydrosilanes such as PhMe2SiH, Ph2MeSiH,
and Ph2SiH2 did not promote hydrosilylation.
Next we extended the metal catalyst candidates for cata-
lytic hydrosilylation to other commercially available first-
row transition-metal salts such as cobalt acetate, nickel ace-
tate, and copper acetate. Although nickel and copper salts
did not show the expected catalytic activity, cobalt(II) ace-
tate strongly promoted hydrosilylation of ketone 2a in com-
bination with (EtO)2MeSiH. The catalyst prepared by heat-
ing cobalt acetate (5.0 mol%) and
a
Bopa ligand
(6.0 mol%) was subjected to hydrosilylation of the ketone
2a at 658C for 24 h (Table 1, entries 7–11). Without the
ligand, the reaction did not take place (Table 1, entry 7).
Addition of the ligands activated the cobalt salt to promote
the reaction to give the desired secondary alcohol in almost
quantitative yield. Surprisingly, Bopa-ph (1d) attained the
highest enantioselectivity of 94% (Table 1, entry 11) com-
pared to 54–70% with the others (Table 1, entries 8–10).
Scheme 2. Asymmetric hydrosilylation of methyl-4-phenylphenyl ketone
(2a).
Use of [CoACHTUNGRTNENG(U acac)2] (acac=acetylacetonato) decreased the
yield (Table 1, entry 12). Use of sodium borohydride gave
3a in both lower yield and lower enantioselectivity (Table 1,
entry 13). In short, we obtained higher enantioselectivities
of up to 73% ee with the iron–Bopa-dpm catalyst and 94%
ee with cobalt–Bopa-ph catalyst along with high product
yields.
Next, we examined other aromatic ketones to establish
the substrate scope under the optimized conditions with
iron–Bopa-dpm and cobalt–Bopa-ph catalysts (Scheme 3,
Table 2). Among the para-substituted phenyl ketones 2b–
2h, the dimethylamino (2b) and morpholino (2c) deriva-
tives gave the highest ee values of over 80% (Table 2, en-
tries 1 and 3). At 408C, reduction of 2b and 2c gave 85 and
pared by heating a mixture of FeACTHNUTRGNENUG(OAc)2 (5.0 mol%) and
Bopa (7.0 mol%) in THF at 658C in the presence of the
ketone. Then the hydrosilane was added and the mixture
was stirred for 24 h. After hydrolytic workup, the product
secondary alcohol 3a was isolated by column chromatogra-
phy. Compared to 61% ee with Bopa-ip, Bopa-tb and Bopa-
dpm gave slightly higher enantioselectivities of 68 and 73%,
respectively (Table 1, entries 2–5). A lower catalyst loading
of 0.5 mol% with Bopa-dpm resulted in almost the same
result as with 5 mol% (Table 1, entry 5). Two equivalents of
the hydrosilane are required to obtain satisfactory yields.
Use of 1.2 equivalents of the silane decreased the yield to
Chem. Eur. J. 2010, 16, 3090 – 3096
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3091

H. Nishiyama et al.
Table 2. Asymmetric hydrosilylation of other ketones with Fe
Bopa-dpm (1c) and Co
(OAc)2/Bopa-ph (1d) catalysts.[a]
ACHTUNGTRENNUNG(OAc)2/
AHCTUNGTRENNUNG
Entry
Ketone Fe(OAc)2/1c
Yield [%] of 3
(ee [%])
U
Co
Yield [%] of 3
(ee [%])
ACHTUNGRTEN(NUNG OAc)2/1d
N
ACHTUNGTRENNUNG
1
2
3
4
5
6
7
8
2b
2b
2c
2c
2d
2e
2 f
2 f
2g
2h
2i
2i
2j
2k
2l
2m
2n
2o
2p
2q
96 (80)
97 (85)[b]
99 (83)
93 (88)[b]
98 (78)
99 (72)
98 (70)
–
99 (68)
93 (64)
99 (54)
–
99 (58)
99 (56)
95 (50)
99 (73)
93 (22)
99 (65)
99 (71)
88 (58)
98 (87)
99 (38)[c]
99 (93)
99 (54)[c]
99 (91)
99 (94)
99 (96)
99 (98)[d]
99 (91)
96 (93)
98 (96)
98 (96)[d]
99 (95)
98 (94)
95 (93)
99 (93)
95 (60)
99 (92)
99 (91)
99 (95)
9
10
11
12
13
14
15
16
17
18
19
20
[a] For Fe cat.: Ketone 2a (1.0 mmol), Fe
(3.0 mol%), (EtO)2MeSiH (2.0 mmol), THF (3.0 mL), 658C, 24 h,
workup with H3O+. For Co cat.: Ketone (1.0 mmol), Co
(OAc)2
ACHTUNGRTEN(NUNG OAc)2 (2.0 mol%), Bopa-dpm
ACHTUNGTRENNUNG
(5.0 mol%), Bopa-ph (6.0 mol%), (EtO)2MeSiH (2.0 mmol), THF
(3.0 mL), 658C, 24 h, workup with KF, TBAF. All products have R abso-
lute configuration. [b] 408C, 96 h. [c] Bopa-ip was used. [d] 408C, 48 h.
On the other hand, the cobalt–Bopa-ph catalyst largely
improved the enantioselectivities (Table 2, column 4). The
dimethylamino (2b) and morpholino (2c) derivatives gave
higher ee values of 87 and 93%, respectively (Table 2, en-
tries 1 and 3). However, as expected, using Bopa-ip de-
creased the enantioselectivities to 38 and 54% (Table 2, en-
tries 2 and 4). Substituted phenyl ketones 2d–2m were re-
duced with an average ee value of about 94% (Table 2, en-
tries 5–16). para-n-Butylphenyl ketone (2 f) and ortho-me-
thoxyphenyl ketone (2i) were subjected the hydrosilylation
at 408C (Table 2, entries 8 and 12). The reaction proceeded
for 48 h to give the corresponding alcohols 3 f and 3i with
98 and 96% ee, respectively. With the exception of a-naph-
thalene derivative 2n, other ketones 2o–2q gave higher
enantioselectivities of up to 91–95% (Table 2, entries 18–
20). Reduction of 2-phenylethyl methyl ketone as a linear
aliphatic ketone was examined under the same conditions
and resulted in a low ee of 15% and quantitative yield.
In summary, the cobalt–Bopa-ph catalyst attained high
enantioselectivities of up to 98% and higher mean ee values
of over 90%. In the context of asymmetric reduction of ke-
tones using chiral cobalt complexes, Yamada et al. reported
efficient methods for catalytic hydroboration with NaBH4/
alcohols or modified borohydrides.[12] With regard to enan-
tioselective hydrosilylation catalyzed by cobalt complex,
Brunner et al reported 56% ee for the reduction of aceto-
phenone with 0.5 mol% of cobalt pyridine complex and
chiral mono-oxazolinylpyridine ligand in the presence of
Scheme 3. Asymmetric hydrosilylation of other ketones.
88% ee, respectively (Table 2, entries 2 and 4). Ketones 2i–
2m bearing meta and ortho substituents gave lower ee
values in the range of 50–73% (Table 2, entries 11–16). Fur-
thermore, a-naphthalene derivative 2n gave the reverse ab-
solute configuration (Table 2, entry 17). Ketones 2o, 2p, and
2q resulted in only 58–73% (Table 2, entries 18–20). Thus,
the highest enantioselectivity achieved with the iron Bopa-
dpm catalyst was 88%. With Beller and co-workersꢁ Fe
Duphos catalyst[5] and Gade and co-workersꢁ Fe bis(pyridyl-
ACHTUNGTRENNUNG
imino)isoindole catalyst,[6] the hydrosilylation of the bulky
2,4,6-trimethylphenyl methyl ketone resulted in 99 and 93%
ee, respectively. However, the iron–Bopa-ip catalyst slowly
promoted reduction of the bulky ketone to give 22% yield
and 5% ee; about 60% of the ketone was recovered.
3092
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 3090 – 3096

Asymmetric Hydrosilylation of Ketones and Enones
FULL PAPER
Ph2SiH2 in 1991,[13] but since then no other asymmetric hy-
drosilylation with cobalt catalysts has been reported.
ly improved the 1,4-reduction in THF and toluene (Table 3,
entries 2–4). CoCl2 was not effective even with the ligand
(Table 3, entry 5).
Asymmetric conjugate hydrosilylation of enones with Co–
Bopa catalysts: Asymmetric conjugate reduction of a,b-un-
saturated carbonyl compounds with chiral Co catalysts has
been intensively studied in combination with boron hydrides
as reducing agents. Pfaltz et al.[14] reported the first asym-
metric conjugate reduction with a chiral Co semicorrin cata-
lyst and NaBH4, followed by Yamada et al.[15] using a Co oxo-
aldiminato catalyst with NaBH4, and Reiser et al.[16] with
CoCl2 and chiral bisoxazoline ligands. For non-asymmetric
reductions, a stoichiometric [Co2(CO)8]/H2O system, which
can promote the conjugate reduction of a,b-unsaturated ke-
tones, was reported by Lee et al.[17]
We next examined the asymmetric reaction with several
b,b-disubstituted enones (8a–e) as substrates (Scheme 5,
Table 4). b-Methylbenzalacetone (8a) resulted in 71% ee
with Bopa-dpm (1c; Table 4, entry 3). The ee values depend
on the substituents of the ligands (Table 4, entries 1–4).
Moderate ee values of 65–75%, were obtained for the other
enones 8b–8e (Table 4, entries 5–8).
We examined the suitability of Co–Bopa catalysts for con-
jugate reduction of enones in combination with
(EtO)2MeSiH. First, we carried out the reaction with benzal-
acetone (5) as substrate enone and Bopa-dm (4) as achiral
ligand (Scheme 4, Table 3). Even without the ligand, the re-
duction proceeded smoothly to give a mixture of 1,4-reduc-
tion product 6 and 1,2-reduction product 7 in 39:61 ratio
(Table 3, entry 1). However, addition of ligand 4 dramatical-
Scheme 5. Asymmetric cobalt-catalyzed conjugate reduction of some
enones.
Table 4. Asymmetric conjugate hydrosilylation of enones with Co-
AHCTUNGTRENNUNG
(OAc)2/Bopa catalysts.[a]
Entry
Bopa
Enone
Yield of 9 [%]
ee of 9 [%]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1c
1c
1c
1c
8a
8a
8a
8a
8b
8c
8d
8e
87
85
90
89
92
90
91
93
42
15
71
8
75
70
65
72
[a] Enone (0.5 mmol), CoACHTNUGTRNEUNG(OAc)2 (5.0 mol%), Bopa-ip (6.0 mol%),
(EtO)2MeSiH (1.5 mmol), toluene (1.0 mL), 658C, 24 h.
Scheme 4. Hydrosilylation of benzalacetone.
We previously reported that the Fe–Bopa catalyst reduces
benzalacetone in 1,2 fashion to give mainly 7 in 80% yield
along with 6 in 4% yield.[4a]
Table 3. Hydrosilylation of benzalacetone (5) with Co
(4) catalyst.[a]
ACHTUNGRTEN(NUNG OAc)2/Bopa-dm
Entry
1[b]
2
Solvent
Yield of 6 [%]
Yield of 7 [%]
Structural analysis of Fe–Bopa and Co–Bopa complexes: It
is important to characterize an active catalyst and its stereo-
chemistry. Therefore, we attempted to isolate the complex
of iron(II) acetate and Bopa-ip, but the mixture did not give
the corresponding complex. However, the reaction of bis-
(oxazolinylphenyl)amine 1a (Bopa-ip) with iron(II) chloride
at 658C did result in the formation of ironACTHNUTRGNE(NUG III) bis(oxazoli-
nylphenyl)amide complex 10 as a green solid in 94% yield
(Scheme 6). Under air, the iron(II) atom was oxidized to an
THF
THF
toluene
toluene
toluene
39
96
99
99
61
0
0
0
–
3
4[c]
5[d]
no reaction
[a] Ketone 5 (1.0 mmol), Co
(EtO)2MeSiH (2.0 mmol), solvent (3.0 mL), 658C, 24 h. [b] No ligand.
[c] (EtO)2MeSiH (1.5 mmol). [d] In place of Co
(5.0 mol%) was used.
ACHTUNGRTEN(NUNG OAc)2 (5.0 mol%), Bopa-dm (6.0 mol%),
ACHTUNGTRNEN(UNG OAc)2, CoCl2
Chem. Eur. J. 2010, 16, 3090 – 3096
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3093

H. Nishiyama et al.
Scheme 6. Preparation of iron chloro and cobalt chloro complexes.
ironACHTUNGTRENNUNG(III) species bearing the N,N,N-tridentate amide ligand.
The structure of complex 10 was confirmed by X-ray analy-
sis to be a trigonal-bipyramidal coordination complex with
C2 symmetry (Figure 1). The two oxazoline rings are situat-
ed at apical positions relative to each other.
The reaction of cobalt(II) chloride and Bopa-ip 1a was
carried out in THF solution. Concentration of the solvent
afforded amine complex 11 as a blue solid. The structure of
11 was determined by X-ray analysis to show trigonal-bipyr-
amidal coordination with divalent cobalt atom and two chlo-
ride ligands at apical and equatorial positions. The oxazoline
rings occupy two equatorial positions. One isopropyl group
showed a disordered configuration.
The catalytic activities of iron and cobalt complexes 10
and 11 were examined for hydrosilylation of the ketone 2
under the same condition as described above. Unfortunately,
neither chloro complex showed catalytic activity, and the
ketone was recovered.
Figure 1. Molecular
structures
of
FeIII
[FeIII
ACHTUNGTRENNUNG
ip)Cl2]bis(oxazolinylphenyl)amide complex 10 (top) and [CoII
ip)Cl2] 11 (bottom).
ACHTUNGTRENNUNG
Conclusion
We have found that the readily prepared chiral bis(oxazoli-
nylphenyl)amines (Bopa) are efficient auxiliaries for iron
and cobalt catalysts which exhibit high activity for asymmet-
ric hydrosilylation of ketones and conjugate hydrosilylation
of enones. Iron and cobalt, first-row elements, are conven-
ient and environmentally friendly metals for asymmetric cat-
alysis. Additionally, hydrosilanes are a safe alternative to hy-
drogen gas in organic synthesis. Theoretical studies are now
underway to elucidate the catalytic mechanism by consider-
ing certain metal hydride species.
Experimental Section
1
General procedures: H and 13C NMR spectra were recorded on a Varian
Mercury 300 spectrometer. 1H and 13C chemical shifts d are reported in
ppm relative to the singlet at d=7.26 ppm and the triplet at d=77.0 ppm
for CDCl3, respectively. Infrared spectra were recorded on a Jasco FR/
IR-230 spectrometer. Optical rotation was measured on
1020NS polarimeter. Bopa ligands 1a, 1b, and 1d were prepared accord-
ing to the method reported by Du, Xu et al..[3a] Fe
(OAc)2 was purchased
from Wako Pure Chemical Industries, Ltd., and Co(OAc)2 from Kishida
a Jasco P-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Chemicals Co. Ltd. HRMS (FAB and EI) was measured on Jeol JMS-700
at Chemical Instrumentation Facility of Nagoya University. Characteriza-
tion data, NMR spectra, and LC charts of the products are listed in the
Supporting Information.
3094
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 3090 – 3096

Asymmetric Hydrosilylation of Ketones and Enones
FULL PAPER
Iron-catalyzed hydrosilylation, typical procedure (Table 2, entries 3 and
Cobalt-catalyzed asymmetric conjugate reduction of 8b: Enone 8b
4): 4’-Morpholinoacetophenone (2c; 205 mg, 1.0 mmol), Bopa-dpm
(87 mg, 0.50 mmol), Bopa-dpm (19.2 mg, 0.030 mmol), and CoACHTUNGTRENNUNG(OAc)2
(19.2 mg, 0.030 mmol), and FeACTHNUTRGNE(UGN OAc)2 (3.5 mg, 0.020 mmol) were placed
(4.4 mg, 0.025 mmol) were placed in a flask. Under argon atmosphere,
toluene (1.0 mL) was added, and the mixture was stirred for 1 h at 658C.
Then, (EtO)2MeSiH (120 mL, 0.75 mmol) was added, and the mixture
was stirred for 24 h at 658C. After concentration, aqueous HCl (2n,
2 mL), THF (1 mL), and MeOH (1 mL) were added at 08C. The mixture
was extracted with ethyl acetate (5ꢂ2.0 mL) and washed with water
(5.0 mL) and brine (5.0 mL). The combined organic layer was dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel with ethyl acetate/
hexane as eluent to give the desired ketone 9b (80.8 mg, 0.46 mmol) in
92% yield (Table 4, entry 5). Colorless oil; [a]2D5 =26.2 (c=1.0, CHCl3);
1H NMR (300 MHz, CDCl3): d=0.79 (t, J=7.2 Hz, 3H), 1.50–1.78 (m,
2H), 2.03 (s, 3H), 2.72–2.80 (m, 2H), 3.02 (m, 1H), 7.18–7.23 (m, 3H),
7.25–7.30 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=12.2, 29.5, 30.8,
43.1, 50.6, 126.1, 127.3, 128.2, 144.0, 207.6 ppm; IR (film):n˜ =1713, 1360,
754, 701 cmÀ1; chromatography: Daicel Chiralcel OJ-H, hexane/2-propa-
nol (99/1, 0.5 mLminÀ1), retention time: 28.6 min (major), 36.0 min
(minor), 75% ee; HRMS (EI): [M+] m/z found: 176.1204; calcd
(C12H16O): 176.1201.
in a flask. Under argon atmosphere, THF (3.0 mL) was added, and the
mixture was stirred for 1 h at 658C. Then, (EtO)2MeSiH (320 mL,
2.0 mmol) was added, and the mixture was stirred for 24 h at 658C. The
reaction was monitored by TLC (ethyl acetate/hexane=1:3, Rf =0.35 for
the ketone, Rf =0.70 for the silylated product). TBAF (THF solution, 1m,
1.0 mL), KF (112 mg), MeOH (1.0 mL), and H2O (1.0 mL) were added at
08C. The mixture was extracted with ethyl acetate (5ꢂ2.0 mL) and
washed with water (5.0 mL) and brine (5.0 mL). The combined organic
layer was dried over anhydrous Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatography on silica
gel with ethyl acetate/hexane as eluent to give the desired alcohol 3c
(205 mg, 0.99 mmol) in 99% yield (Table 2, entry 3). The same reaction
was carried out at 408C for 96 h to give the desired alcohol 3c (193 mg,
0.93 mmol) in 93% yield (Table 2, entry 4). White solid; m.p. 93.3–
95.38C; [a]2D5 =45.5 (c=1.0, CHCl3); 1H NMR (300 MHz, CDCl3): d=
1.48 (d, J=6.3 Hz, 3H), 1.82 (brs, 1H), 3.15 (dd, J=4.5, 6.3 Hz, 4H),
3.86 (dd, J=4.5, 6.3 Hz, 4H), 4.84 (q, J=6.0 Hz, 1H), 6.90 (m, 2H),
7.29 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=25.0, 49.5, 66.9, 70.0,
115.5, 126.2, 137.0, 150.4 ppm; IR (film): n˜ =3423 (br), 2966, 1610, 1514,
1231, 1116 cmÀ1; chromatography: Daicel Chiralcel OB-H, hexane/2-
propanol (90/10, 1.0 mLminÀ1), retention time: 21.5 min (major),
25.0 min (minor), 88% ee; HRMS (FAB): [M+] m/z found: 207.1254;
calcd (C12H17NO2): 207.1259.
Preparation of [FeCl2ACTHNUTRGNEUNG(Bopa-ip)] (10): FeCl2 (25.4 mg, 0.20 mmol) and
Bopa-ip (78.4 mg, 0.20 mmol) were placed in a flask under argon atmos-
phere. THF (1.0 mL) was added, and the mixture was stirred at 658C for
1 h to give a green solution. The solution was filtered and concentrated
to give a green solid, which was recrystalized from dichloromethane and
hexane to give 10 as a green solid (93.8 mg, 0.187 mmol, 94% yield);
m.p. 245–2468C; IR (KBr disk): n˜ =3067, 2957, 2871 cmÀ1; elemental
analysis calcd (%) for C24H28Cl2N3O2Fe: C 55.73, H 5.46, N 8.12; found:
Cobalt-catalyzed hydrosilylation, typical procedure (Table 2, entries 7
and 8): 4’-n-Butylacetophenone (2 f; 176 mg, 1.0 mmol), Bopa-ph
(27.6 mg, 0.06 mmol), and CoACHTUNTRGNEUNG(OAc)2 (8.9 mg, 0.05 mmol) were placed in
a flask. Under argon atmosphere, THF (3.0 mL) was added, and the mix-
ture was stirred for 1 h at 658C. Then (EtO)2MeSiH (320 mL, 2.0 mmol)
was added, and the mixture was stirred for 24 h at 658C. The reaction
was monitored by TLC (ethyl acetate/hexane 1/3, Rf =0.7 for the ketone,
Rf =0.9 for the silylated product). TBAF (THF solution, 1m, 1.0 mL), KF
(112 mg), MeOH (1.0 mL), and H2O (1.0 mL) were added at 08C. The
mixture was extracted with ethyl acetate (5ꢂ2.0 mL) and washed with
water (5.0 mL) and brine (5.0 mL). The combined organic layer was
dried over anhydrous Na2SO4 and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel with
ethyl acetate/hexane as eluent to give the desired alcohol 3 f (176 mg,
0.99 mmol) in 99% yield (Table 2, entry 7). The same reaction was car-
ried out at 408C for 48 h to give the desired alcohol 3 f (176 mg,
0.99 mmol) in 99% yield. Colorless oil; [a]2D5 =38.4 (c=1.0, CHCl3);
1H NMR (300 MHz, CDCl3): d=0.99 (t, J=7.2 Hz, 3H), 1.40 (m, 2H),
1.48 (d, J=6.3 Hz, 3H), 1.63 (m, 2H), 2.63 (t, J=7.5 Hz, 2H), 4.83 (q,
J=6.3 Hz, 1H), 7.16 (d, J=7.8 Hz, 2H), 7.27 ppm (d, J=7.8 Hz, 2H);
13C NMR (75 MHz, CDCl3): d= 14.1, 22.5, 25.1, 33.8, 35.4, 70.1, 125.1,
1
C 55.51, H 5.44, N 7.87; H NMR could not be measured.
Preparation of [CoCl2ACTHNUTRGNEUNG(Bopa-ip)] (11): CoCl2 (64.9 mg, 0.50 mmol) and
Bopa-ip (196 mg, 0.50 mmol) were placed in a flask. THF (3.0 mL) was
added, and the mixture stirred at 608C for 3 h. The solvent was removed
under reduced pressure, and the residue dissolved in dichloromethane.
The solution was filtered through filter paper and was concentrated to
1 mL. Then hexane was slowly added to precipitate a dark green solid,
which was recrystallized from ethyl acetate and a small amount of di-
chloromethane to give an ultramarine solid (258 mg, 0.49 mmol) in 98%
yield; m.p. 244–2468C (decomp); IR (KBr disk):n˜ =3437 (br), 3214, 2961,
1626, 1489, 1375, 1246 cmÀ1
; elemental analysis calcd (%) for
C24H29Cl2N3O2Co·0.25CH2Cl2: C 53.78, H 5.30, N 7.76; found: C 54.14, H
5.50,
N
7.51; HRMS (FAB): [M+] m/z found: 520.0978; calcd
1
(C24H29Cl2N3O2Co): 520.0969; H NMR could not be measured.
X-ray diffraction study: The diffraction data were collected on a Bruker
SMART APEX CCD diffractometer with graphite-monochromated
MoKa radiation (l=0.71073 ꢃ). An empirical absorption correction was
applied by using SADABS. The structure was solved by direct methods
and refined by full-matrix least-squares techniques on F2 by using
SHELXTL. One of the iPr groups in 11 is disordered over two positions,
which were refined in the ratio of 58:42. All non-hydrogen atoms were
refined with anisotropic displacement parameters except the iPr group in
11. All hydrogen atoms were located on calculated positions and refined
as rigid groups. Refinement details for 10: C24H28Cl2FeN3O2; Mr =517.24;
T=153(2) K; crystal system monoclinic; space group P21; a=10.6822(6),
b=8.7164(5), c=13.2058(7) ꢃ, b=95.6620(10)8, V=1223.60(12) ꢃ3, Z=
128.2, 141.8, 142.7 ppm; IR (film):n˜ =3352 (br), 2961, 2927, 1082 cmÀ1
;
Chromatography: Daicel Chiralcel OD-H, hexane/2-propanol (95/5,
0.5 mLminÀ1), retention time: 11.6 min (major), 12.6 min (minor), 98%
ee; HRMS (FAB): [M+] m/z found: 178.1361; calcd (C12H18O): 178.1358.
Cobalt-catalyzed conjugate reduction of benzalacetone: Benzalacetone
(5; 146 mg, 1.0 mmol), Bopa-dm (21.8 mg, 0.06 mmol), and CoACTHNUTRGNEUNG(OAc)2
(8.9 mg, 0.05 mmol) were placed in a flask. Under argon atmosphere, tol-
uene (3.0 mL) was added, and the mixture was stirred for 1 h at 658C.
Then, (EtO)2MeSiH (240 mL, 1.5 mmol) was added, and the mixture was
stirred for 24 h at 658C. TBAF (THF solution, 1m, 1.0 mL), KF (112 mg),
MeOH (1.0 mL), and H2O (1.0 mL) were added at 08C. The mixture was
extracted with ethyl acetate (5ꢂ2.0 mL) and washed with water (5.0 mL)
and brine (5.0 mL). The combined organic layer was dried over anhy-
drous Na2SO4 and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel with ethyl acetate/
hexane as eluent to give the desired ketone 6 (146 mg, 0.99 mmol) in
99% yield (Table 3, entry 3). Colorless oil; 1H NMR (300 MHz, CDCl3):
d=2.16 (s, 3H), 2.73–2.85 (m, 2H), 2.87–2.97 (m, 2H), 7.15–7.27 (m,
3H), 7.28–7.36 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d 29.8, 30.2,
45.2, 1125.8, 128.0, 128.2, 140.7, 207.4 ppm; IR (film): n˜ =1714, 1149, 752,
2, 1calcd =1.404 MgmÀ3, m=0.860 mmÀ1, F
ACTHNUTRGNE(NUG 000)=538, crystal size=0.60ꢂ
0.50ꢂ0.50 mm, q range=1.55 to 28.238; index ranges: À14ꢀhꢀ14, À7ꢀ
kꢀ 11, À17ꢀl 17; reflections collected 9217, independent reflections
4258 [RACTHUNRTGNEUNG(int)=0.0184], completeness to q=28.238, 99.7%; max./min.
transmission 1.000000/0.731983; data/restraints/parameters 4258/1/293;
goodness of fit on F2 1.075; final R indices [I>2s(I)]: R1=0.0249, wR2=
0.0641; R indices (all data): R1=0.0256, wR2=0.0644; largest diff. peak/
hole 0.434/À0.234 eꢃÀ3. Refinement details for 11: C24H28Cl2CoN3O2;
Mr =520.32; T=153(2) K; crystal system: monoclinic; space group: P21;
a=10.875(3), b=9.230(3), c=12.263(3) ꢃ, b=101.019(5)8, V=
1208.1(6) ꢃ3, Z=2, 1calcd =1.430 MgmÀ3 m=0.957 mmÀ1
, , FACHTUGNTRNE(NUGN 000)=540,
crystal size=0.40ꢂ0.20ꢂ0.20 mm, q range=1.69 to 28.368; index ranges:
À6ꢀhꢀ14, À12ꢀkꢀ 12, À16ꢀlꢀ 14; reflections collected 8832, inde-
701 cmÀ1
148.0888.
;
HRMS (EI): [M+] m/z found: 148.0891; calcd (C10H12O):
Chem. Eur. J. 2010, 16, 3090 – 3096
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
3095

H. Nishiyama et al.
pendent reflections 5788 [R
(int)=0.0221], completeness to q=28.368,
348, 551–558; c) V. Coeffard, M. Aylward, P. J. Guiry, Angew.
Chem. 2009, 121, 9316–9319; Angew. Chem. Int. Ed. 2009, 48, 9152–
9155.
99.4%; max./min. transmission 1.000000/0.775499; data/restraints/parame-
ters 5788/1/304; goodness of fit on F2 1.022; final R indices [I>2s(I)]:
R1=0.0381, wR2=0.0902;
R
indices (all data): R1=0.0457, wR2=
[3] a) S.-F. Lu, D.-M. Du, S.-W. Zhang, J. Xu, Tetrahedron: Asymmetry
2004, 15, 3433–3441; b) D.-M. Du, S.-F. Lu, T. Fang, J. Xu, J. Org.
Chem. 2005, 70, 3712–3715; c) S.-F. Lu, D.-M. Du, J. Xu, Org. Lett.
2006, 8, 2115–2118; d) S.-F. Lu, D.-M. Du, J. Xu, S.-W. Zhang, J.
Am. Chem. Soc. 2006, 128, 7418–7419; e) H. Liu, J. Xu, D.-M. Du,
Org. Lett. 2007, 9, 4725–4728; f) H. Liu, S.-F. Lu, J. Xu, D.-M. Du,
Chem. Asian J. 2008, 3, 1111–1121.
0.0937; largest diff. peak/hole 0.644 and À0.242 eꢃÀ3. CCDC-752895 (10)
and CCDC-752896(11) contain the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
Synthesis of Bopa-dpm ACHTUNGTRENNUNG
(1c): According to the literature method,[3a] the
[4] a) H. Nishiyama, A. Furuta, Chem. Commun. 2007, 760–762. Relat-
ed catalytic hydrosilylation: b) A. Furuta, H. Nishiyama, Tetrahe-
dron Lett. 2008, 49, 110–113; c) T. Inagaki, Y. Yamada, L. T. Phong,
A. Furuta, J. Ito, H. Nishiyama, Synlett 2009, 253–256.
[5] a) N. S. Shaikh, S. Enthaler, K. Junge, M. Beller, Angew. Chem.
2008, 120, 2531–2535; Angew. Chem. Int. Ed. 2008, 47, 2497–2501;
b) N. S. Shaikh, K. Junge, M. Beller, Org. Lett. 2007, 9, 5429–5432.
[6] B. K. Langlotz, H. Wadepohl, L. H. Gade, Angew. Chem. 2008, 120,
4748–4752; Angew. Chem. Int. Ed. 2008, 47, 4670–4674.
[7] a) A. M. Tondreau, E. Lobkovsky, P. J. Chirik, Org. Lett. 2008, 10,
2789–2792; b) A. M. Tondreau, J. M. Darmon, B. M. Wile, S. K.
Floyd, E. Lobkovsky, P. J. Chirik, Organometallics 2009, 28, 3928–
3940.
starting amino alcohol (S)-2-amino-3,3-diphenylpropan-1-ol was prepared
from (1R,2R)-(À)-2-amino-1-phenyl-1,3-propanediol. A solution of com-
mercially available 2,2’-iminodibenozic acid (771 mg, 3.0 mmol; Aldrich
30895-25G) in thionyl chloride (4.5 mL) was heated at 808C for 1 h.
Excess thionyl chloride was removed under reduced pressure and azeo-
tropically with CH2Cl2 (3ꢂ10 mL) to give the bis(acid chloride) as a
crude solid, a solution of which in CH2Cl2 (10 mL) was added to a solu-
tion of the amino alcohol (1.47 g, 6.6 mmol) and Et3N (2.1 mL) in CH2Cl2
(25 mL) at 08C. The mixture was stirred for 4 h at room temperature to
form the corresponding bis(amide alcohol), and the mixture was again
cooled to 08C. Then, Et3N (4.2 mL) and methanesulfonyl chloride
(1.2 mL, 15 mmol) were added, and the mixture was stirred for 12 h at
room temperature. For workup, aqueous K2CO3 (1m, 3 mL) was added at
08C, and the mixture extracted with CH2Cl2 (3ꢂ20 mL). The combined
organic layer was dried over Na2SO4 and concentrated under reduced
pressure. The residual solid was purified by column chromatography with
hexane/ethyl acetate as eluent to give the desired compound 1c (1.39 g,
2.17 mmol) in 72% yield; white solid, m.p. 105–1068C; [a]2D0 =À184 (c=
[8] S. Enthaler, B. Hagemann, G. Erre, K. Junge, M. Beller, Chem.
Asian J. 2006, 1, 598–604.
[9] a) C. Sui-Seng, F. Freutel, A. J. Lough, R. H. Morris, Angew. Chem.
2008, 120, 954–957; Angew. Chem. Int. Ed. 2008, 47, 940–943; b) A.
Mikhailine, A. J. Lough, R. H. Morris, J. Am. Chem. Soc. 2009, 131,
1394–1395; c) N. Meyer, A. J. Lough, R. H. Morris, Chem. Eur. J.
2009, 15, 5605–5610.
[10] a) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2007, 129, 5816–5817;
b) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2009, 131, 2499–2507.
[11] Review: R. H. Morris, Chem. Soc. Rev. 2009, 38, 2282–2291.
[12] a) H. Sato, H. Watanabe, Y. Ohtsuka, T. Ikeno, S. Fukuzawa, T.
Yamada, Org. Lett. 2002, 4, 3313–3316; b) T. Yamada, T. Nagata,
K. D. Sugi, K. Yorozu, T. Ikeno, Y. Ohtsuka, D. Miyazaki, T. Mu-
kaiyama, Chem. Eur. J. 2003, 9, 4485–4509; c) A. Kokura, S.
Tanaka, T. Ikeno, T. Yamada, Org. Lett. 2006, 8, 3025–3027.
[13] H. Brunner, K. Amberger, J. Organomet. Chem. 1991, 417, C63–
C65.
[14] a) U. Leutenegger, A. Madin, A. Pfaltz, Angew. Chem. 1989, 101,
61–62; Angew. Chem. Int. Ed. Engl. 1989, 28, 60–61; b) M. Misun,
A. Pfaltz, Helv. Chim. Acta 1996, 79, 961–972; c) P. von Matt, A.
Pfaltz, Tetrahedron: Asymmetry 1991, 2, 691–700.
[15] a) T. Nagata, K. Yorozu, T. Yamada, T. Mukaiyama, Angew. Chem.
1995, 107, 2309–2311; Angew. Chem. Int. Ed. Engl. 1995, 34, 2145–
2147. Related reduction: b) Y. Ohtsuka, T. Ikeno, T. Yamada, Tetra-
hedron: Asymmetry 2003, 14, 967–970.
1.0, CHCl3); IR (KBr): n˜ =1641, 1581, 1455, 738, 697 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d=3.80 (t, J=9.0 Hz, 2H), 3.85 (d, J=9.0 Hz, 2H),
4.20 (t, J=9.0 Hz, 2H), 4.60 (q, J=9.0 Hz, 2H), 6.88 (m, 2H), 7.01–7.30
(m, 22H), 7.40 (m, 2H), 7.78 (m, 2H), 11.0 ppm (s, 1H, NH); 13C NMR
(75 MHz, CDCl3): d=56.9, 70.1, 70.9, 115.1, 117.7, 119.2, 125.8, 126.4,
127.5, 128.3, 128.6, 128.9, 130.2, 131.1, 142.0, 142.1, 143.2, 162.2 ppm; ele-
mental analysis calcd C44H37N3O2: C 82.60, H 5.83, N 6.57; found: C
82.61, H 5.85, N 6.38.
Acknowledgements
This work was partly supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and Technology
of Japan (Concerto Catalysts, 460:18065011) and the Japan Society for
the Promotion of Science (18350049).
[1] Reviews on nitrogen-based ligands for asymmetric catalysis“: a) M.
Gꢄmez, G. Muller, M. Rocamora, Coord. Chem. Rev. 1999, 193–195,
769–835; b) F. Fache, E. Schulz, M. L. Tommasino, M. Lemaire,
Chem. Rev. 2000, 100, 2159–2231; c) A. K. Ghosh, P. Mathivanan, J.
Cappiello, Tetrahedron: Asymmetry 1998, 9, 1–45; d) G. Desimoni,
G. Faita, P. Quadreil, Chem. Rev. 2003, 103, 3119–3154; e) G. Desi-
moni, G. Faita, K. A. Jørgensen, Chem. Rev. 2006, 106, 3561–3651;
f) H. A. McManus, P. J. Guiry, Chem. Rev. 2004, 104, 4151–4202.
[2] a) H. A. McManus, P. J. Guiry, J. Org. Chem. 2002, 67, 8566–8573;
b) H. A. McManus, P. G. Cozzi, P. J. Guiry, Adv. Synth. Catal. 2006,
[16] C. Geiger, P. Kreitmeier, O. Reiser, Adv. Synth. Catal. 2005, 347,
249–254.
[17] H.-Y. Lee, M. An, Tetrahedron Lett. 2003, 44, 2775–2778.
[18] D. A. Klumpp, S. L. Aquirre, G. V. Sanchez, Jr., S. J. de Leon, Org.
Lett. 2001, 3, 2781–2784.
Received: November 13, 2009
Published online: January 29, 2010
3096
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 3090 – 3096