Asymmetric conjugate reduction of α,β-unsaturated ketones and esters with chiral rhodium(2,6-bisoxazolinylphenyl) catalysts

Article abstract of DOI:10.1002/chem.200500841

New asymmetric conjugate reduction of β,β-disubstituted α,β-unsaturated ketones and esters was accomplished with alkoxylhydrosilanes in the presence of chiral rhodium(2,6-bisoxazolinylphenyl) complexes in high yields and high enantioselectivity. (E)-4-Phenyl-3-penten-2- one and (E)-4-phenyl-4-isopropyl-3-penten-2-one were readily reduced at 60°C in 95% ee and 98 % ee, respectively, by 1 mol % of catalyst loading. (EtO) ₂MeSiH proved to be the best hydrogen donor of choice. tert-Butyl (E)-β-methylcinnamate and β-isopropylcinnamate could also be reduced to the corresponding dihydrocinnamate derivatives up to 98% ee.

Full text of DOI:10.1002/chem.200500841

FULL PAPER
DOI: 10.1002/chem.200500841
Asymmetric Conjugate Reduction of a,b-Unsaturated Ketones and Esters
with Chiral Rhodium(2,6-bisoxazolinylphenyl) Catalysts
Yoshinori Kanazawa, Yasunori Tsuchiya, Kazuki Kobayashi, Takushi Shiomi,
Jun-ichi Itoh, Makoto Kikuchi, Yoshihiko Yamamoto, and Hisao Nishiyama*[a]
Abstract: New asymmetric conjugate
reduction of b,b-disubstituted a,b-unsa-
turated ketones and esters was accom-
plished with alkoxylhydrosilanes in the
presence of chiral rhodium(2,6-bisoxa-
zolinylphenyl) complexes in high yields
and high enantioselectivity. (E)-4-
phenyl-4-isopropyl-3-penten-2-one were
readily reduced at 608C in 95% ee and
98% ee, respectively, by 1 mol% of
catalyst loading. (EtO)2MeSiH proved
to be the best hydrogen donor of
choice. tert-Butyl (E)-b-methylcinna-
mate and b-isopropylcinnamate could
also be reduced to the corresponding
dihydrocinnamate derivatives up to
98% ee.
Keywords: asymmetric catalysis
·
conjugate reduction · hydrosilanes ·
oxazolines · rhodium
Phenyl-3-penten-2-one
and
(E)-4-
Introduction
disclosed in 1989 by Pfaltz et al. with semicorrin–cobalt cata-
lyst and borohydride.[2] In 1998, Yamada et al. reported the
aldiminate–cobalt complex (S)-MPAC as an efficient cata-
Asymmetric conjugate reduction (ACR) of b,b-disubstituted
a,b-unsaturated carbonyl compounds is a very important
practical synthetic method (Scheme 1), leading to a variety
Scheme 1. Asymmetric conjugate reduction of a,b-unsaturated carbonyl
compounds.
of optically active compounds bearing an asymmetric center
at the b-position.[1] In order to resolve this issue, several
chiral transition-metal catalysts in combination with hydride
donors, such as borohydride or hydrosilanes, have been de-
veloped to demonstrate their high efficiency. However, the
scope of metal catalysts has been limited only to cobalt and
copper catalysts. The pioneering approach of ACR of a,b-
unsaturated esters, carboxamides, nitriles, and sulfones, was
lyst with modified borohydride for ACR of carboxamides.[3]
Very recently, Reiser et al. reported that the azabis(oxazo-
line) is a superior ligand for cobalt-catalyzed ACR of esters
and carboxamides.[4] On the other hand, as for copper cata-
lysts, chiral copper–hydride species generated by reaction of
CuCl/NaOtBu/TolBINAP and PMHS (PMHS=polymethyl-
hydrosiloxane) was reported by Buchwald et al. in 1999 to
show higher enantioselectivity for esters, and the system was
then applied to ACR giving optically active cyclopenta-
nones, lactones, lactams, and b-azaheterocyclic acid deriva-
tives.[5] Around the same time, Lipshutz et al. also reported
that copper catalysts bearing chiral bisphosphine, JOSI-
[a] Y. Kanazawa, Dr. Y. Tsuchiya, K. Kobayashi, T. Shiomi, Dr. J.-i. Itoh,
Prof. M. Kikuchi, Prof. Y. Yamamoto, Prof. H. Nishiyama
Department of Applied Chemistry
Graduate School of Engineering, Nagoya University
Chikusa, Nagoya 464–8603 (Japan)
Fax : (+81)52-789-3209
E-mail: hnishi@apchem.nagoya-u.ac.jp
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2006, 12, 63 – 71
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
63

Scheme 2. a) RhCl3·3H2O, NaHCO3, in MeOH/H2O, 608; b) [{Rh(cy-
clooctene)2Cl}2], NaHCO3, in CHCl3, reflux; R=iPr a, sBu b, iBu c, tBu
d, Bn e, Ph f.
PHOS, PPF-P(t-Bu)2, and DTBM-SEGPHOS, were effec-
tive toward ACR of cycloalkenones, acyclic enones, and
esters.[6] In parallel, a variety of conjugate reduction systems
have been also developed by using nonchiral copper cata-
lysts.[7] More noteworthy are chiral metal-free organocata-
lysts for ACR of a,b-unsaturated aldehydes in the combina-
tion of dihydropyridine as a hydride donor, reported inde-
pendently very recently by MacMillan et al. and List et al.[8]
We have already reported the synthesis of a chiral 2,6-
bis(2-oxazolinyl)phenyl skeleton (abbreviated as Phebox) as
a C2-symmetric tridentate N-C-N ligand and its transition-
metal complexes, which exhibit high potential in several
high stereo- and enantioselective reactions as a new type of
transition-metal Lewis acid.[9] We have recently reported
that chiral Rh–Phebox catalysts show a catalytic activity for
hydrosilylation of monosubstituted and a,b-disubstituted al-
kenes with alkoxyhydrosilanes.[10] On this basis, we consid-
ered that the asymmetric conjugate reduction of a,b-unsatu-
rated carbonyl compounds might be accomplished in the
same way by asymmetric hydrosilylation with Rh–Phebox
catalysts. We report here highly efficient ACR of a,b-unsa-
turated ketones and esters. The case of the esters has been
already reported in preliminary communication.[11]
was thought that coordination of the nitrogen ligand 1 to
the monovalent rhodium complex accelerated oxidation by
chloroform to form a RhCl3–(Phebox/H, N,N-bidentate)
À
species, which might readily cause a C H bond cleavage
giving the complex 2. The complexes 2 were then readily
converted to the corresponding acetate complexes 3 by
treatment with an excess of silver acetate.
Conjugate reduction of a,b-unsaturated ketones: The conju-
gate reduction of a,b-unsaturated ketones commonly suffers
from concurrent 1,2-reduction giving allylic alcohols. How-
ever, in 1982 Ojima et al. discovered almost complete regio-
selective reduction of a,b-unsaturated ketones by hydrosily-
lation using Wilkinson catalyst [RhCl(Ph3P)3].[12] In that
system, it is important to choose a hydrosilane as a hydride
donor. Use of Et3SiH or EtMe2SiH leads to conjugate re-
duction (1,4-reduction) followed by hydrolysis giving ke-
tones, whereas Ph2SiH2 leads exclusively to 1,2-reduction
giving allylic alcohols. Keinan et al. also developed the effi-
cient hydrosilative 1,4-reduction systems with palladium-
and molybdenum-based catalytic systems, [Pd(Ph3P)4]/
ZnCl2/Ph2SiH2 and [Mo(CO)6]/PhSiH3, respectively.[13] Alter-
natively, the copper–hydride systems have recently been re-
ported by several research groups, as mentioned above.[7]
First, we examined the reduction of benzalacetone with
the Rh–Phebox catalysts 2a and 3a (1 mol%; Table 1). The
catalytic reactions with hydrosilanes, such as (EtO)2MeSiH,
Et2MeSiH, and Me2PhSiH, proceeded smoothly at 508C
within 2 h. The acetate complex 3a proved to be superior
for 1,4-reduction to the chloride complex 2a, giving the
ketone 4 in addition to Et2MeSiH. No asymmetric induction
was observed for the 1,2-reduction product, (E)-4-phenyl-3-
buten-2-ol (5), which was obtained in the case with 2a.
As we thus found the catalytic system for the exclusive
conjugate reduction, we in turn carried out an asymmetric
case to adopt (E)-4-phenyl-3-penten-2-one (6) as a standard
probe. The reaction of the ketone 6 (1.0 mmol) was carried
out with 1 mol% of the acetate complex 3a and 1.5 equiva-
lents of the hydrosilanes in a toluene (1.0 mL) at 608C
(Table 2). After hydrolysis treatment, the product ketone 7
Results and Discussion
Convenient synthesis ofRh–Phebox complexes by simple
À
C H bond activation: The starting ligand 1 was synthesized
in two steps by condensation of isophthaloyl chloride and an
optically active aminoalcohol, followed by oxazoline forma-
tion with methanesulfonyl chloride and triethylamine. Heat-
ing of a mixture of the ligand, RhCl3(H2O)3, and NaHCO3
in methanol and water gave the corresponding chloride
complex 2 in a moderate yield of approximately 50%
(Scheme 2). As yet, we have been unable to improve this
À
C H bond activation process to attain high yield. As an al-
ternative convenient synthetic method, we recently found
that heating a mixture of [{RhI(cylcooctene)2Cl}2] and the
ligand in CHCl3 gave the complex 2 in a moderate yield. It
64
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Chem. Eur. J. 2006, 12, 63 – 71

Asymmetric Catalysis
FULL PAPER
Table 1. Conjugate reduction of benzalacetone.
gave the conjugate reduction product 7 in 92–97% yields
(Table 2, entries 1, 2, and 4); the % ee reached 93%
(entry 4). At room temperature, the reaction proceeded
smoothly and resulted in an increase of ee to 95% (entries 3
and 5). Use of (EtO)2PhSiH gave 90% ee (entry 6). Howev-
er, alkylhydrosilanes, such as Et2MeSiH, only promoted 1,2-
reduction in 5–24% and in addition to a decrease of %ee
(entries 7–9). Surprisingly, although Ph2SiH2 selectively pro-
moted 1,2-reduction with a Wilkinson catalyst, as demon-
strated by Ojima et al.,[12] Rh–Phebox catalyst 3a mainly
leads to the conjugate reduction in 86% with 88% ee
(entry 10). On the other hand, the reaction with the chloride
complex 2a and (EtO)3SiH barely proceeded even after
long reaction time to give 30% yield and lower selectivity
(entry 11). By using the other acetate complexes 3b–f, the
reduction proceeded smoothly to give 7 in high yield (en-
tries 12–16). Although the case of 3d (R=tBu) did not
result in asymmetric induction in the 1,4:1,2 ratio of 85:15,
other catalysts gave a middle range of 73–95% ee. The re-
verse absolute configuration of the product was confirmed
by use of (R,R)-Phebox skeleton (entry 17).
Catalyst
Silane
1,4-Reduction
1,2-Reduction
yield of 5 [%]
yield of 4 [%]
2a
2a
2a
3a
3a
3a
(EtO)2MeSiH
Et2MeSiH
Me2PhSiH
(EtO)2MeSiH
Et2MeSiH
72
95
51
95
95
97
24
<1
41
1
<1
1
Me2PhSiH
Table 2. Asymmetric conjugate reduction of (E)-4-phenyl-3-penten-2-
one (6).[a]
Next, we examined the scope of substrate ketones with
the catalyst 3a and (EtO)2MeSiH at room temperature
(Table 3). With the increase in bulkiness of the ketone sub-
stituents from methyl to Et<iPr<Ph, the ee decreased from
95 to 82% (for 9, 11, and 13). When the methyl group at the
b-position of 6 was changed to a bulky isopropyl group, the
reduction proceeded very slowly. It took 24 h to complete
the reduction of 14 at room temperature and also resulted
in a drastic decrease of ee to 40%. However, at 608C the
catalysis proceeded smoothly for one hour to give the high-
est ee of 98% (for 15). With a phenylethyl group at the b-
position as in 17 the ee was 95%, but with a 4-methyl-3-pen-
tenyl and cyclohexyl group it decreased it to 89 and 65%,
respectively (for 19, 21). On the other hand, the reduction
of (Z)-a,b-unsaturated ketone (Z)-6 took place smoothly for
2 h to generate a reverse in the absolute configuration, but
significant decrease of ee to 51%. In the case of (Z)-17, the
ee was 91% with reverse absolute configuration.
Entry
Cat.
Hydrosilane
Yield [%]
1,4/1,2
ee [%]
1
2
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
2a
3b
3c
3d
3e
3 f
3a’
(EtO)Me2SiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)3SiH
(EtO)3SiH
(EtO)2PhSiH
Et2MeSiH
Me2PhSiH
MePh2SiH
Ph2SiH2
(EtO)3SiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
92
96
97
97
97
96
94
91
92
92
30
92
94
94
93
97
96
96/4
100/0
100/0
100/0
100/0
100/0
76/24
91/9
54
91
95
93
95
90
14
26
51
88
8
95
76
1
73
81
95
3[b]
4
5[b]
6
7
8
9
95/5
10[c]
11[d]
12[b]
13[b]
14[e]
15
86/14
76/24
100/0
100/0
85/15
100/0
100/0
100/0
16[b]
17[f]
[a] Cat. (0.01 mmol,
1 mol%), ketone 6 (1.0 mmol), hydrosilane
(1.5 mmol), toluene (1 mL), 608C, 1 h. [b] At room temperature for 1 h.
[c] 608C, 2 h. [d] 608C, 21 h. [e] 608C, 5 h. [f] 3a’, (R,R)-Phebox catalyst;
the absolute configuration of the product was S.
Conjugate reduction of a,b-unsaturated esters: The ACR of
b,b-disubstituted a,b-unsaturated esters was also conducted
by the same method as described above. As a standard
ester, (E)-ethyl 3-phenylbut-2-enoate (22), was chosen to be
subjected to the catalysis with Rh–Phebox complexes 2a
and 3a with several hydrosilanes (Scheme 4). Among the al-
koxyhydrosilanes investigated, (EtO)2MeSiH with 1 mol%
of 3a gave 23 in the highest ee (97%) at 308C (Table 4,
with R absolute configuration was isolated in high yield by
column chromatography (Scheme 3). Although (EtO)Me2-
SiH produced a slight amount of the corresponding 1,2-re-
duction product, (EtO)2MeSiH and (EtO)3SiH exclusively
Scheme 3. Asymmetric conjugate reduction of (E)-4-phenyl-3-penten-2-
one (6).
Scheme 4. Asymmetric conjugate reduction of (E)-ethyl 3-phenylbut-2-
enoate (22).
Chem. Eur. J. 2006, 12, 63 – 71
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www.chemeurj.org
65

H. Nishiyama et al.
Table 3. Asymmetric conjugate reduction of a,b-unsaturated ketones.[a]
Similarly, the substrate scope of the esters was demon-
strated with the catalyst 3a and (EtO)2MeSiH (Table 5). In
most cases, the reactions were retarded at 308C. Therefore,
the reactions were carried out at 608C. The bulky ester moi-
eties such as iPr and tBu slightly increased the ee up to 98%
Substrate
Product
Yield [%]
ee [%]
R=Et
8
R=Et
9
98
95
94
92
82
96[b]
97
Table 5. Asymmetric conjugate reduction of a,b-unsaturated esters.[a]
R=iPr
R=Ph
10
12
R=iPr
R=Ph
11
13
99
Substrate
T [8C]/t Product
[h]
Yield
[%]
ee
[%]
95[c]
97[d]
40
98
R=iPr
R=tBu 26
24
60/1
60/1
R=iPr
R=tBu 27
25
98[b]
99
97
98[b]
97
97
94
95
89
65
R=Et
R=iPr 30
28
60/1
60/0.5
R=Et
R=iPr 31
29
99
97
96
98
60/1
40/1
96
96
93
91[b]
90[e]
51
91
60/0.5
60/19
96
81
92
43
96
[a] Cat. 3a (0.01 mmol, 1 mol%), ketone (1.0 mmol), (EtO)2MeSiH
(1.5 mmol), toluene (1 mL), RT, 1 h. [b] (EtO)3SiH (1.5 mmol), RT, 1 h.
[c] RT, 24 h. [d] 608C, 1 h. [e] RT, 2 h.
60/1
86
81
[a] Cat. 3a (0.01 mmol,
1 mol%), ester (1.0 mmol), (EtO)2MeSiH
(1.5 mmol), toluene (1 mL). [b] Data were corrected from those previous-
ly reported in reference [11].
Table 4. Asymmetric conjugate reduction of (E)-ethyl 3-phenylbut-2-
enoate (22).[a]
Entry
Cat.
Hydrosilane
T [8C]/t [h]
Yield [%]
ee [%]
1
2
3
3a
3a
3a
3a
2a
2a
2a
3a
2a
2a
2e
(EtO)Me2SiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)2MeSiH
(EtO)3SiH
60/3
60/1
30/1
60/24
60/5
40/24
60/2
60/0.5
80/12
80/24
60/2
94
96
97
89
95
99
97
95
30
55
96
86
96
97
94
95
95
95
93
15
64
69
(for 25, 27), and the b-substituents Et and iPr also increased
the ee to 98% (for 29, 31). However, alkyl substituents for
32 and 34 decreased the ee to 91–93% (for 33, 35), whereas
the reduction of the isomers (Z)-22 and (Z)-32 resulted in
reverse of absolute configuration with decrease of ee. In the
case of (Z)-22, rapid isomerization from Z to E was ob-
served during the reaction by an NMR experiment. The iso-
merization can explain the decrease in ee. In this context,
Buchwald et al. attained high ee for the reduction of (Z)-22
in 92% ee with a copper–BINAP catalyst.[5e]
4[b]
5
6
7[c]
8
9
10
11
Et2MeSiH
Me2PhSiH
(EtO)2MeSiH
[a] Cat. (0.01 mmol), 22 (1.0 mmol), hydrosilane (1.5 mmol), toluene
(1 mL). [b] 22 (5.0 mmol). [c] AgBF4 (0.02 mmol).
Limitations ofsubstrate scope : We have examined a variety
of b,b-disubstituted a,b-unsaturated carbonyl compounds. In
conclusion, cyclic ketones and lactones could not be smooth-
ly reduced under the same standard conditions at room tem-
perature to 608C, as described above.
entry 3). Even with decrease of the catalyst loading to 0.2
mol%, the ee was only slightly decreased to 94% (entry 4).
The chloride catalyst 2a and the cationic complex were also
effective and gave 95% ee (entries 6, 7). However, the com-
bination of 2a and alkylhydrosilanes is not preferable due to
decrease of the yields and ee, even at higher temperature
808C (entries 9, 10). The benzyl catalyst 2e decreased the ee
to 69% (entry 11).
Structure ofthe catalyst : The molecular structure of 3a
could be analyzed by X-ray crystallography to show its C2-
symmetric form (Figure 1). The Phebox skeleton meridio-
66
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Chem. Eur. J. 2006, 12, 63 – 71

Asymmetric Catalysis
FULL PAPER
face of the a-carbon atom to the rhodium metal and subse-
quent hydride attack on the b-carbon atom. The Re-face co-
ordination illustrated in structure II is disfavored by steric
repulsion between the carbonyl group and the isopropyl
group on the ligand.
Conclusion
We have found that chiral rhodium(bisoxazolinylphenyl)
complexes can act as potent catalysts for the asymmetric
conjugate reduction of acyclic b,b-disubstituted a,b-unsatu-
rated ketones and esters with diethoxymethylsilane in high
enantioselectivity. This reaction will provide a potential
route to bioactive chiral carbonyl compounds with a b-asym-
metric center.
Figure 1. Molecular structure of complex 3a. Selected bond lengths [Š]
À
À
À
and angles [8]: Rh C 1.9234(18), Rh N1 2.0579(16), Rh N2 2.0877(17),
À
À
À
Rh O1 2.2317(15), Rh O2 2.0473(14), Rh O3 2.0265 (13); C-Rh-O1
176.06(7), C-Rh-O2 87.29(7), C-Rh-O3 90.26(6), C-Rh-N1 79.50(7), C-
Rh-N2 87.73(6), N1-Rh-N2 158.36(7).
Experimental Section
General: Column chromatography was performed with
a silica gel
column (Merck Silica gel 60) and ethyl acetate/hexane as eluent, unless
otherwise mentioned. H and 13C NMR spectra were obtained at 258C on
1
À
nally binds to the rhodium atom with an Rh C bond lengths
a Varian Mercury 300 spectrometer. 1H NMR chemical shifts are report-
ed in d units, in ppm relative to the singlet at 7.26 ppm for chloroform.
13C NMR spectra are reported in terms of chemical shift (d, ppm) relative
to the triplet at d=77.0 ppm for CDCl3 as an internal standard. Infrared
spectra were recorded on a JASCO FT/IR-230 spectrometer. Absolute
toluene and hydrosilanes were purchased from TCI. The substrate ke-
tones 6, 8, 10, 12, 14, 16, 18, and 20, were prepared from the correspond-
ing esters via Weinrebꢁs amide and subsequent alkylation; see Supporting
Information. The substrate esters 22, 24, 26, 28, 30, 32, and 34 were pre-
pared by the Horner–Wadsworth–Emmons reaction according to a previ-
ously reported procedure; see Supporting Information.[2b,5a,7j] The ester
22 can also be purchased from Aldrich.
À
of 1.92 Š and Rh N bond lengths of 2.05 and 2.09 Š. The
À
bond angle of N-Rh-N is 158.368. The bond length of Rh
O1aqua1 is 2.23 Š. These data are similar to those for the
chloride complex 2e, previously reported.[9d]
Stereochemical course ofthe asymmetric induction : We
present here a hypothetical mechanism and stereochemical
course of the reaction: the starting rhodium(iii) complex is
reduced by an excess of the hydrosilane to the correspond-
ing rhodium(i) species, which react with the hydrosilane to
form the [(hydrido)(silyl)rhodium(iii)Phebox] species as a
catalyst. The a,b-unsaturated carbonyl compound ap-
Preparation of[( S,S)-Phebox-iPr]H (1a): A solution of isophthaloyl di-
chloride (1.02 g, 5.0 mmol) in dichloromethane (20 mL) was slowly added
to a solution of l-valinol (1.03 g, 10.0 mmol) and triethylamine (7.6 g,
75 mmol) in dichloromethane (40 mL) at 08C. The mixture was stirred at
room temperature for 1 h. Formation of the intermediate diamide–dialco-
hol was monitored by TLC examination; Rf =0.4 (ethyl acetate/metha-
nol=10:1). Then, methanesulfonyl chloride (1.26 g, 11 mmol) was added
at 08C, and the mixture was stirred at room temperature for 5 h. Forma-
tion of the product 1a was monitored by TLC examination; Rf =0.8
(ethyl acetate/hexane=3:1). At 08C, aqueous potassium carbonate (1n,
ca. 30 mL) was added and the mixture was extracted with ethyl acetate.
The organic layer was washed with saturated brine, was dried over mag-
nesium sulfate, and was concentrated. The crude product was purified by
column chromatography to give 1a in 87% yield (1.30 g, 4.33 mmol) as a
colorless solid. For full analytical data for 1a and an alternative synthetic
route to 1a, see a procedure reported by Bolm et al.[14]
À
proaches to the active intermediate, the Rh H species I
(Figure 2). The hydride attack to the b-carbon atom gives
The preparation procedures of 1b, 1c, 1d, 1e, and 1 f were similar to that
of 1a.
Figure 2. Hypothetical stereochemical course.
[(S,S)-Phebox-sBu]H (1b): Yield: 82% (1.35 g) from l-isoleucinol
(1.17 g, 10 mmol) and isophthaloyl dichloride (1.0 g, 5.0 mmol). For full
analytical data for 1b, see reference [14].
the R absolute configuration. The reductive elimination with
[(S,S)-Phebox-iBu]H (1c): Yield: 84% (1.38 g) from l-leucinol (1.17 g,
10 mmol) and isophthaloyl dichloride (1.0 g, 5.0 mmol); colorless solid:
m.p. 47–488C; [a]2D5 =À107.08 (c=1.03 in CHCl3); 1H NMR (CDCl3): d=
8.47 (t, J=1.5 Hz, 1H), 8.04 (dd, J=7.8, 1.5 Hz, 2H), 7.36 (t, J=7.8 Hz,
1H), 4.51 (dd, J=9.3, 7.8 Hz, 2H), 4.28–4.38 (m, 2H), 3.99 (t, J=7.8 Hz,
2H), 1.76–1.90 (m, 2H), 1.66–1.75 (m, 2H), 1.32 (m, 2H), 0.98 (d, J=
6.6 Hz, 6H), 0.96 ppm (d, J=6.6 Hz, 6H); 13C NMR (CDCl3): d=22.71,
22.81, 25.41, 45.52, 65.11, 73.08, 127.8, 128.0, 128.1, 130.5, 163.3 ppm; IR
À
the silyl group via the Rh O enolate produces the silylenol
ether or the ketene silylacetal, which is then converted to
the reduction product by hydrolysis. The absolute S configu-
ration from the (Z)-carbonyl compound can also be ex-
plained by the structure I. Therefore, the absolute configura-
tion observed is based on selective coordination of the Si-
Chem. Eur. J. 2006, 12, 63 – 71
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
67

H. Nishiyama et al.
(KBr disk): n˜ =1652, 1574 cmÀ1
C20H28N2O2 (328.45): C 73.14, H 8.59, N 8.53; found: C 73.25, H 9.02, N
8.61.
;
elemental analysis calcd (%) for
Preparation of[Rh{( S,S)-Phebox-iPr}(OAc)2]·H2O (3a): A mixture of 2a
(246 mg, 0.50 mmol) and silver acetate (334 mg, 2.0 mmol) in dichlorome-
thane (15 mL) was stirred for 15 h at room temperature. The concentrat-
ed residue was purified by silica-gel chromatography with ethyl acetate/
methanol as eluent to give 3a (232 mg, 0.43 mmol) in 86% yield as a yel-
lowish-orange solid. M.p. 2358C (decomp); 1H NMR (CDCl3): d=7.43
(d, J=7.2 Hz, 2H), 7.30 (t, J=7.2 Hz, 1H), 5.08 (brs, 2H), 4.60–4.80 (m,
4H), 4.38 (m, 2H), 2.50 (m, 2H), 1.71 (s, 6H), 0.97 (d, J=7.2 Hz, 6H),
0.75 ppm (d, J=7.2 Hz, 6H); 13C NMR (CDCl3): d=14.79, 19.13, 23.42,
[(S,S)-Phebox-tBu]H (1d): Yield: 81% (1.34 g) from l-tert-leucinol
(1.17 g, 10 mmol) and isophthaloyl dichloride (1.0 g, 5.0 mmol); colorless
solid: m.p. 123–1248C; [a]2D6 =À123.98 (c=1.01 in CHCl3); 1H NMR
(CDCl3): d=8.51 (t, J=1.8 Hz, 1H), 8.06 (dd, J=7.8, 1.8 Hz, 2H), 7.44
(t, J=7.8 Hz, 1H), 4.35 (dd, J=10.2, 8.7 Hz, 2H), 4.24 (dd, J=8.7,
7.8 Hz, 2H), 4.06 (dd, J=10.2, 7.8 Hz, 2H), 0.95 ppm (s, 18H); 13C NMR
(CDCl3): d=25.94, 34.11, 68.79, 76.29, 127.9, 128.1, 128.2, 130.7,
162.4 ppm; IR (KBr disk): n˜ =1653, 1587 cmÀ1; elemental analysis calcd
(%) for C20H28N2O2 (328.45): C 73.14, H 8.59, N 8.53; found: C 73.16, H
9.08, N 8.44.
29.50, 67.72, 71.27, 122.9, 127.5, 131.5, 171.3, 182.3 ppm (d, JRh-C
=
25.7 Hz); IR (KBr disk): n˜ =1615, 1395 cmÀ1; elemental analysis calcd
(%) for C22H31N2O7Rh (538.40): C 49.08, H 5.80, N 5.20; found: C 49.22,
H 5.79, N 5.14.
The preparation procedures of 3b, 3c, 3d, 3e, and 3 f were similar to that
of 3a.
[(S,S)-Phebox-Bn]H (1e): Yield: 81% (1.60 g) from l-phenylalaninol
(1.51 g, 10 mmol) and isophthaloyl dichloride (1.0 g, 5.0 mmol); colorless
solid: m.p. 106–1078C; [a]2D6 =À4.88 (c=0.99 in CHCl3); 1H NMR
(CDCl3): d=8.50 (t, J=1.8 Hz, 1H), 8.09 (dd, J=7.8, 1.8 Hz, 2H), 7.47
(t, J=7.8 Hz, 1H), 7.20–7.34 (m, 10H), 4.60 (m, 2H), 4.36 (dd, J=9.6,
8.4 Hz, 2H), 4.15 (dd, J=8.4, 7.5 Hz, 2H), 3.25 (dd, J=13.8, 5.1 Hz, 2H),
2.74 ppm (dd, J=13.8, 9.0 Hz, 2H); 13C NMR (CDCl3): d=41.71, 67.85,
71.85, 126.3, 127.9, 128.2, 128.3, 129.0, 130.8, 137.6, 163.0 ppm; IR (KBr
disk): n˜ =1649, 1575 cmÀ1; elemental analysis calcd (%) for C26H24N2O2
(396.48): C 78.76, H 6.10, N 7.07; found: C 78.86, H 6.20, N 6.87.
[Rh{(S,S)-Phebox-sBu}(OAc)2]·H2O (3b): Yield: 80% (227 mg); yellow
solid: m.p. 1938C (decomp); 1H NMR (CDCl3): d=7.58 (d, J=7.5 Hz,
2H), 7.31 (t, J=7.5 Hz, 1H), 4.71 (dd, J=10.2, 8.7 Hz, 2H), 4.64 (dd, J=
8.7, 6.6 Hz, 2H), 4.45–4.51 (m, 2H), 3.03 (brs, 2H), 2.24–2.37 (m, 2H),
1.29–1.45 (m, 2H), 1.13–1.27 (m, 2H), 1.01 (t, J=7.5 Hz, 6H), 0.68 ppm
(d, J=6.9 Hz, 6H); 13C NMR (CDCl3): d=11.81, 12.03, 23.97, 26.73,
35.90, 66.44, 71.00, 123.0, 127.3, 131.6, 171.6, 182.0, 188.8 ppm (d, JRh-C
=
23.9 Hz); IR (KBr disk): n˜ =1614, 1483 cmÀ1; elemental analysis calcd
(%) for C24H35N2O7Rh (566.45): C 50.89, H 6.23, N 4.95; found: C 50.84,
H 6.38, N 4.85.
[(S,S)-Phebox-Ph]H (1 f): Yield: 80% (1.48 g) from (S)-2-phenylglycinol
(1.37 g, 10 mmol) and isophthaloyl dichloride (1.0 g, 5.0 mmol); colorless
solid: m.p. 120–1248C; [a]2D5 =À74.48 (c=1.04 in CHCl3); 1H NMR
(CDCl3): d=8.69 (t, J=1.5 Hz, 1H), 8.20 (dd, J=7.8, 1.5 Hz, 2H), 7.53
(t, J=7.8 Hz, 1H), 7.27–7.40 (m, 10H), 5.41 (dd, J=10.2, 8.4 Hz, 2H),
4.82 (dd, J=10.2, 8.1 Hz, 2H), 4.30 ppm (dd, J=8.4, 8.1 Hz, 2H);
13C NMR (CDCl3): d=70.16, 74.94, 126.6, 127.5, 127.8, 128.4, 128.5,
128.6, 131.2, 142.0, 163.9 ppm; IR (KBr disk): n˜ =1649, 1575 cmÀ1; ele-
mental analysis calcd (%) for C24H20N2O2 (368.43): C 78.24, H 5.47, N
7.60; found: C 78.10, H 5.69, N 7.52.
[Rh{(S,S)-Phebox-iBu}(OAc)2]·H2O (3c): Yield: 85% (242 mg); yellow
solid: m.p. 1478C (decomp); 1H NMR (CDCl3): d=7.57 (d, J=7.5 Hz,
2H), 7.27 (t, J=7.5 Hz, 1H), 6.12 (brs, 2H), 4.92 (dd, J=9.0, 8.1 Hz,
2H), 4.50 (dd, J=8.1, 7.8 Hz, 2H), 4.34–4.44 (m, 2H), 2.16 (m, 2H), 1.70
(m, 2H), 1.69 (s, 6H), 1.31 (m, 2H), 1.00 ppm (d, J=6.6 Hz, 6H);
13C NMR (CDCl3): d=21.89, 23.58, 23.70, 25.52, 43.38, 61.59, 76.42,
122.9, 127.3, 131.8, 171.2, 182.0, 188.5 ppm (d, JRh-C =24.5 Hz); IR (KBr
disk): n˜ =1611, 1479 cmÀ1
;
elemental analysis calcd (%) for
C24H35N2O7Rh (566.45): C 50.89, H 6.23, N 4.95; found: C 50.79, H 6.50,
N 4.81.
Simple preparation of[Rh{( S,S)-Phebox-iPr}Cl2]·H2O (2a): RhCl3·3H2O
(579 mg, 2.2 mmol), the ligand 1a (600 mg, 2.0 mmol), sodium bicarbon-
ate (168 mg, 2.0 mmol) were placed in a flask. After addition of methanol
(20 mL) and water (1 mL), the mixture was heated at 608C for 5 h. The
concentrated residue was purified by silica-gel chromatography with
ethyl acetate/hexane (2:1 to 1:1) as eluent to give 2a in 56% yield
(549 mg, 1.12 mmol). As an alternative method, [{Rh(cyclooctene)2Cl}2]
was used in place of RhCl3·3H2O. The mixture of the rhodium complex
(180 mg, 0.25 mmol) and ligand 1a (150 mg, 0.50 mmol) was heated at
608C for 6 h in a CHCl3 (10 mL). After chromatography, complex 2a was
obtained in 46% (113 mg, 0.23 mmol). Full characterization data of 2a
and the alternative preparation methods with Phebox-SnMe3 were re-
ported in reference [9d].
[Rh{(S,S)-Phebox-tBu}(OAc)2]·H2O (3d): Yield: 85% (241 mg); yellow
solid: m.p. 2838C (decomp); 1H NMR (CDCl3): d=7.57 (d, J=7.5 Hz,
2H), 7.28 (t, J=7.5 Hz, 1H), 4.65–4.76 (m, 4H), 4.10 (dd, J=9.9, 7.5 Hz,
2H), 3.11 (brs, 2H), 1.77 (s, 6H), 1.07 ppm (s, 18H); 13C NMR (CDCl3):
d=23.32, 25.94, 34.12, 72.21, 72.36, 122.9, 128.0, 131.4, 171.8, 181.7,
185.2 ppm (d, JRh-C =27.3 Hz); IR (KBr disk): n˜ =1615, 1490, 1401 cmÀ1
;
elemental analysis calcd (%) for C24H35N2O7Rh (566.45): C 50.89, H 6.23,
N 4.95; found: C 51.05, H 6.24, N 4.78.
Rh[(S,S)-Phebox-bn](OAc)2(H2O) (3e); 82% yield (261 mg); yellow
solid: mp. 1048C (dec); 1H NMR (CDCl3): d=7.62 (d, J=7.8 Hz, 2H),
7.22–7.35 (m, 11H), 6.19 (brs, 2H), 4.54–4.76 (m, 6H), 3.69 (dd, J=13.5,
3.0 Hz, 2H), 2.62 (dd, J=13.5, 9.3 Hz, 2H), 1.72 (s, 6H) ppm; 13C NMR
(CDCl3): d=24.05, 40.03, 63.99, 75.27, 123.2, 126.7, 127.7, 128.7, 129.2,
131.7, 136.8, 172.2, 182.3, 188.8 (d, JRh-C =23.9 Hz); IR (KBr disk): n˜ =
1610, 1488, 1393 cmÀ1; elemental analysis calcd (%) for C30H31N2O7Rh
(634.48): C 56.79, H 4.92, N 4.42; found: C 57.05, H 4.94, N 4.14.
The preparation procedures of 2b (541 mg, 52%), 2c (554 mg, 53%), 2d
(246 mg, 24%), 2e (608 mg, 52%), and 2 f (557 mg, 50%) were similar to
that of 2a. For full analytical data for 2d, 2e, and 2 f, see reference [9d].
[Rh{(S,S)-Phebox-sBu}Cl2]·H2O (2b): Pale yellow solid: m.p. 2688C
(decomp); 1H NMR (CDCl3): d=7.58 (d, J=7.8 Hz, 2H), 7.28 (t, J=
7.8 Hz, 1H), 4.75 (dd, J=10.2, 9.0 Hz, 2H), 4.68 (dd, J=9.0, 7.2 Hz, 2H),
4.36 (ddd, J=10.2, 7.2, 3.0 Hz, 2H), 2.15–2.23 (m, 2H), 1.94 (s, 2H),
1.17–1.43 (m, 4H), 0.99 (dd, J=7.5, 7.2 Hz, 6H), 0.90 ppm (d, J=6.6 Hz,
6H); 13C NMR (CDCl3): d=12.09, 12.60, 27.02, 35.95, 65.94, 71.09, 123.1,
127.8, 131.4, 170.6, 180.1 ppm (d, JRh-C =23.9 Hz); IR (KBr disk): n˜ =
[Rh{(S,S)-Phebox-Ph}(OAc)2](H2O) (3 f): Yield: 81% (244 mg); yellow
solid: m.p. 3018C (decomp); 1H NMR (CDCl3): d=7.69 (d, J=7.5 Hz,
2H), 7.36 (t, J=7.5 Hz, 1H), 7.28–7.37 (m, 10H), 5.39 (dd, J=10.2,
7.8 Hz, 2H), 5.16 (dd, J=10.2, 9.0 Hz, 2H), 4.78 (dd, J=9.0, 7.8 Hz, 2H),
4.73 (brs, 2H), 1.44 ppm (s, 6H); 13C NMR (CDCl3): d=23.60, 66.67,
78.32, 123.0, 127.8, 128.3, 128.5, 131.6, 138.6, 172.2, 181.0, 189.8 ppm (d,
1617, 1481 cmÀ1
; elemental analysis calcd (%) for C20H29Cl2N2O3Rh
(519.27): C 46.26, H 5.63, N 5.39; found: C 46.21, H 5.92, N 5.15.
J
Rh-C =24.5 Hz); IR (KBr disk): n˜ =1613, 1487, 1394 cmÀ1; elemental anal-
ysis calcd (%) for C28H27N2O7Rh (606.43): C 55.46, H 4.49, N 4.62;
found: C 55.41, H 4.43, N 4.27.
[Rh{(S,S)-Phebox-iBu}Cl2]·H2O (2c): Pale yellow solid: m.p. 2878C
(decomp); 1H NMR (CDCl3): d=7.58 (d, J=7.8 Hz, 2H), 7.30 (t, J=
7.8 Hz, 1H), 4.91–4.97 (m, 2H), 4.51–4.57 (m, 2H), 4.28–4.38 (m, 2H),
2.65 (brs, 2H), 2.06–2.15 (m, 2H), 1.51–1.72 (m, 4H), 1.00 (d, J=6.6 Hz,
6H), 0.99 ppm (d, J=6.6 Hz, 6H); 13C NMR (CDCl3): d=21.68, 23.80,
Conjugate reduction of a,b-unsaturated ketones
Reduction ofbenzalacetone (Table 1)
: Hydrosilane (1.5 mmol) was
slowly added to a mixture of benzalacetone (146 mg, 1.0 mmol) and the
catalyst 2a (4.9 mg, 0.01 mmol) or 3a (5.4 mg, 0.01 mmol) in toluene
(1.0 mL) at 508C. The mixture was stirred for 0.5–2 h, and the solvent
was removed under reduced pressure. THF (1 mL), MeOH (1 mL), KF
(116 mg, 2.0 mmol), and tetrabutylammonium fluoride (TBAF, 0.3 mmol)
25.76, 43.12, 61.43, 76.19, 123.6, 128.1, 131.1, 170.0, 177.4 ppm (d, JRh-C
=
26.2 Hz); IR (KBr disk): n˜ =1615, 1478 cmÀ1; elemental analysis calcd
(%) for C20H29Cl2N2O3Rh (519.27): C 46.26, H 5.63, N 5.39; found: C
46.38, H 5.56, N 5.35.
68
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 63 – 71

Asymmetric Catalysis
FULL PAPER
in THF (0.3 mL) were added to the residueat 08C. The mixture was stir-
red for 1 h. After extraction with ethyl acetate and concentration, the res-
idue was purified by silica-gel chromatography with ethyl acetate/hexane
to give a mixture of 4-phenyl-2-butanone (4) and (E)-4-phenyl-3-buten-2-
ol (5). The ratio of 4 and 5 was determined by 1H NMR spectroscopy;
(CDCl3): d=2.14 (s, CH3 for 4), 1.38 ppm (d, CH3 for 5).
(S)-4,8-Dimethyl-7-nonen-2-one (19):[24] Yield: 97% (164 mg, 0.97 mmol),
colorless oil. No 1,2-reudction product was obtained. GLPC, Alltech
Chiraldex G-TA (60 kPa, 808C), Rt =56.5 min (minor), 57.7 min (major),
89% ee for S; [a]D22 =À13.88 (c=1.03 in CHCl3); lit.[24a] [a]2D0 =+9.448 (c=
2.50 in CHCl3) for R; lit.[24b] [a]2D4 =À10.78 (c=1.00 in EtOH) for S. NMR
and IR spectra were consistent with previously reported data.[24]
(R)-4-Cyclohexyl-2-pentanone (21):[25] Yield: 94% (158 mg, 0.94 mmol),
Reduction of( E)-4-phenyl-3-penten-2-one (6) (Table 2, entry 3): Dieth-
oxymethylsilane (201 mg, 1.5 mmol) was slowly added by a syringe to a
mixture of compound 6 (160 mg, 1.0 mmol) and the catalyst 3a (5.4 mg,
0.01 mmol) in toluene (1.0 mL) at room temperature. The mixture was
stirred for 1 h and the solvent was removed under reduced pressure. The
residue was treated with hydrochloric acid (4n, 1 mL), MeOH (1 mL),
and THF (1 mL) at 08C for 1 h. After extraction with ethyl acetate and
concentration, the residue was purified by silica-gel chromatography with
ethyl acetate/hexane to give the product (R)-4-phenyl-2-pentanone (7;
97%, 158 mg, 0.97 mmol) as colorless oil. The ee was determined by
chiral HPLC analysis [DAICEL CHIRALCEL OJ-H column,
colorless oil. No 1,2-reduction product was obtained. DAICEL CHIRAL-
PAK AS-H column, 0.5 mLminÀ1
, iPrOH/hexane 1:99, Rt =11.5 min
(minor), 12.3 min (major), 65% ee for R; [a]2D5 =À4.378 (c=1.06 in
CHCl3), according to Science Finder, (S)-(+); lit.[25] [a]D24 =+5.48 (c=1.03
in C6H6). Spectroscopic data were consistent with previously reported
data.[25]
(S)-4-Phenyl-2-pentanone (7) from (Z)-6: Yield: 90% (147 mg,
0.90 mmol), colorless oil; 51% ee for S; [a]2D7 =+21.38 (c=1.0 in CHCl3).
(R)-4-Methyl-6-phenyl-2-hexanone (17) from (Z)-16: Yield: 96%
(182 mg, 0.96 mmol), colorless oil; 91% ee for R; [a]2D8 =+20.88 (c=1.0
in CHCl3).
0.5 mLminÀ1
,
iPrOH/hexane 1:99, Rt =26.8 min (minor), 29.2 min
(major)]: 95% ee for R; [a]2D0 =À40.88 (c=1.0 in CHCl3); lit.[15a] [a]D20
=
Conjugate reduction of a,b-unsaturated esters
+408 (c=0.5 in CHCl3) for S; lit.[15b] [a]D20 =+38.88 (c=0.4 in CHCl3),
97%ee for S. Spectroscopic data were consistent with previously reported
data in reference [15a].
Reduction of( E)-ethyl 3-phenylbut-2-enoate (22) (Table 4, entry 2): Di-
ethoxymethylsilane (201 mg, 1.5 mmol) was slowly added to a mixture of
the ester 22 (190 mg, 1.0 mmol) and the catalyst 3a (5.4 mg, 0.01 mmol)
in toluene (1.0 mL) at 608C. The mixture was stirred for 1 h and then
treated with hydrochloric acid (1N, 1 mL). After extraction with ethyl
acetate and concentration, the residue was purified by silica-gel chroma-
tography with ethyl acetate/hexane to give the product, ethyl (R)-3-phe-
nylbutanoate (23; 184 mg, 96%, 0.96 mmol) as a colorless oil. The ee was
determined by chiral HPLC analysis [DAICEL CHRALCEL OB
For other entries in Table 2, the procedures were the same as described
above for entry 3; scale and conditions were described in the footnote of
Table 2.
Reduction ofother a,b-unsaturated ketones (1.0mmol) listed in Table 3:
The reactions were performed by the same procedure described above
for entry 3 in Table 2 for 6.
(R)-5-Phenyl-3-hexanone (9):[16] Yield: 98% (172 mg, 0.98 mmol), color-
less oil. No 1,2-reduction product was obtained. DAICEL CHIRALCEL
AD-H column, 0.5 mLminÀ1, iPrOH/hexane 1:99, Rt =9.6 min (minor),
10.4 min (major), 95% ee for R; [a]2D5 =À49.58 (c=1.0 in CHCl3); lit.[16]
[a]2D2 =À56.48 (c=1.0 in benzene) for R. NMR and IR spectroscopic data
were consistent with that previously reported.[16]
column, 0.5 mLminÀ1
,
iPrOH/hexane 1:99, Rt =14.1 min (major),
16.8 min (minor)], 95.9% ee for R; [a]2D6 =À24.78 (c=1.12 in CHCl3);
lit.[4a] [a]D25 =+198 (c=1.1 in CHCl3), 90% ee for R. NMR spectra were
consistent with previously reported data.[4,5a,7j]
Reduction ofother a,b-unsaturated esters (1.0mmol) listed in Table 5.
The reactions were performed by the same procedure as above described
for 22.
(R)-2-Methyl-5-phenyl-3-hexanone (11):[17] 97% (185 mg, 0.97 mmol),
colorless oil. No 1,2-reduction product was obtained. DAICEL CHIRAL-
CEL AD-H column, 0.5 mLminÀ1., i-PrOH/hexane (1:99), Rt =8.9 min.
(minor), 9.8 min. (major), 92% ee for R (by analogy to 9); [a]2D1 =À30.58
(c=1.0 in CHCl3). Neither spectroscopic data nor [a]D data were found
Isopropyl (R)-3-phenylbutanoate (25): Yield: 98% (203 mg, 0.98 mmol),
colorless oil. Chiral HPLC analysis: DAICEL CHRALCEL OB column,
0.2 mLminÀ1
,
iPrOH/hexane 2:98, Rt =22.8 min (major), 25.2 min
(minor), 97% ee for R. [a]2D6 =À29.08 (c=1.1 in CHCl3). 1H NMR
(CDCl3): d=7.17–7.31 (m, 5H), 4.95 (sept, J=3.3 Hz, 1H), 3.27 (ddq, J=
15.3, 15.0, 7.2 Hz, 1H), 2.58 (dd, J=15.3, 7.2 Hz, 1H), 2.51 (dd, J=15.0,
7.2 Hz, 1H), 1.30 (d, J=7.2 Hz, 3H), 1.17 (d, J=6.3 Hz, 3H), 1.12 ppm
(d, J=6.3 Hz, 3H); 13C NMR (CDCl3): d=17.40, 17.48, 17.54, 32.33,
38.96, 60.71, 63.11, 121.8, 122.3, 123.9, 141.2, 167.3 ppm; IR (KBr, film):
n˜ =1730 cmÀ1; elemental analysis calcd (%) for C13H18O2 (206.28): C
75.69, H, 8.80; found: C 75.46, H 8.82.
1
in reference [17]. H NMR (CDCl3): d=7.26–7.32 (m, 2H), 7.16–7.23 (m,
3H), 3.35 (m, 1H), 2.76 (dd, J=16.5, 6.6 Hz, 1H), 2.67 (dd, J=16.5,
8.1 Hz, 1H), 2.48 (m, 1H), 1.26 (d, J=6.9 Hz, 3H), 1.04 (d, J=6.9 Hz,
3H), 0.98 ppm (d, J=6.9 Hz, 3H); 13C NMR (CDCl3): d=17.92, 18.10,
21.86, 35.24, 41.31, 48.95, 126.1, 126.7, 128.3, 146.4, 213.2 ppm; IR (KBr,
film): n˜ =1712 cmÀ1; elemental analysis calcd (%) for C13H18O (190.28): C
82.06, H 9.53; found: C 81.88, H 9.71.
(R)-1,3-Diphenyl-1-butanone (13):[18] Yield: 99% (222 mg, 0.99 mmol),
colorless oil. No 1,2-reduction product was obtained. DAICEL CHIRAL-
CEL AD-H column. 0.5 mLminÀ1
, iPrOH/hexane 1:30, Rt =12.6 min
(minor), 14.9 min (major), 82% ee for R; [a]2D5 =À13.58 (c=1.0 in CCl4);
lit.[19a] [a]D24 =À138 (c=1.02 in CCl4), 75% ee for R; lit.[19b] [a]2D5 =+12.68
(c=2.62 in CCl4) for S; lit.[19c] [a]D20 =À14.88 (c=1.2 in CCl4) for R. Spec-
troscopic data of NMR and IR were consistent with previously reported
data.[18]
tert-Butyl (R)-3-phenylbutanoate (27): 217 mg (99%, 0.99 mmol), color-
less oil. Chiral HPLC analysis: DAICEL CHRALCEL OD-H column,
0.3 mLminÀ1
,
iPrOH/hexane 1:99, Rt =15.3 min (major), 16.5 min
(minor), 98% ee for R. [a]2D6 =À20.68 (c=1.2 in CHCl3). 1H NMR
(CDCl3): d=7.16–7.31 (m, 5H), 3.22 (ddq, J=15.3, 15.0, 7.2 Hz, 1H),
2.53 (dd, J=15.3, 7.2 Hz, 1H), 2.46 (dd, J=15.0, 7.2 Hz, 1H), 1.35 (s,
9H), 1.29 ppm (d, J=7.2 Hz, 3H); 13C NMR (CDCl3): d=17.60, 23.67,
32.47, 39.82, 75.80, 121.8, 122.4, 123.9, 141.4, 167.2 ppm; elemental analy-
sis calcd (%) for C14H20O2 (220.31): C 76.33, H, 9.15; found: C 76.31, H
9.26.
(S)-5-Methyl-4-phenyl-2-hexanone (15):[20,21] Yield: 97% (185 mg,
0.97 mmol), colorless oil. No 1,2-reduction product was obtained.
Ethyl (R)-3-phenylpentanoate (29): Yield: 99% (206 mg, 0.99 mmol),
DAICEL CHIRALCEL OJ-H column, 0.5 mLminÀ1
, iPrOH/hexane
colorless oil. Chiral HPLC analysis: DAICEL CHRALCEL OJ-H
1:99, Rt =18.9 min (minor), 23.6 min (major), 98% ee for S;[22] [a]D24
=
column, 0.7 mLminÀ1
,
iPrOH/hexane 1:99, Rt =15.5 min (major),
À38.98 (c=0.97 in CHCl3); lit.[20] [a]D20 =À338 (c=1.12 in CHCl3). NMR
12.5 min (minor), 97% ee for R; [a]2D6 =À18.38 (c=1.1 in CHCl3); lit.[5a]
[a]2D5 =+188 (c=1.1 in CHCl3), 90% ee for S. NMR spectra were consis-
tent with previously reported data.[5a]
data were consistent with previously reported data.[20]
(S)-4-Methyl-6-phenyl-2-hexanone (17)[23]
0.97 mmol), colorless oil. No 1,2-reduction product was obtained.
DAICEL CHIRALPAK AD-H column, 1.0 mLminÀ1
iPrOH/hexane
:
Yield: 97% (185 mg,
Ethyl (S)-4-methyl-3-phenylpentanoate (31): Yield: 97% (213 mg,
0.97 mmol), colorless oil. Chiral GC analysis: Alltec Chiraldex G-TA,
1058C, 60 kPa, Rt =63.6 min (minor), 65.3 min (minor), 98% ee for S;
[a]2D6 =À25.48 (c=1.0 in CHCl3). The ester 31 was converted to the corre-
sponding aldehyde by reduction with DIBAL. The aldehyde showed
,
0.5:99.5, Rt =16.1 min (major), 23.4 min (minor), 95%ee for S; [a]D22
=
À21.78 (c=1.0 in CHCl3); lit.[23] minus specific rotation for S. Spectro-
scopic date were consistent with previously reported data.[23]
Chem. Eur. J. 2006, 12, 63 – 71
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www.chemeurj.org
69

H. Nishiyama et al.
minus rotation; lit.[26], [a]D26 =À23.18 (c=0.94 in C6H6) for (3S)-(À)-4-
methyl-3-phenylpentanal. 1H NMR(CDCl3): d=7.13–7.29 (m, 5H), 3.96
(q, J=7.2 Hz, 2H), 2.84–2.92 (m, 1H), 2.77 (dd, J=15.0, 5.4 Hz, 1H),
2.58 (dd, J=14.7, 9.9 Hz, 1H), 1.86 (dsep, J=6.6, 6.6 Hz, 1H), 1.06 (t, J=
7.2 Hz, 3H), 0.95 (d, J=6.9 Hz, 3H), 0.76 ppm (d, J=6.9 Hz, 3H);
13C NMR(CDCl3): d=14.1, 20.4, 20.7, 33.2, 38.7, 49.0, 60.1, 126.1, 127.9,
128.1, 142.7, 172.6 ppm; IR (KBr, film): n˜ =1735 cmÀ1; elemental analysis
calcd (%) for C14H20O2 (220.31): C 76.33, H 9.15; found: C 76.10, H 9.29.
For preparation of the starting substrate 30, see reference [27].
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Ethyl (S)-3-methyl-5-phenylpentanoate (33): At 608C; yield: 96%
(211 mg, 0.96 mmol), colorless oil. Chiral HPLC analysis: DAICEL
CHIRALCEL OJ-H column, 0.5 mLminÀ1, EtOH/hexane (3:97), Rt =
10.1 min (minor), 10.6 min (major), 91% ee for S; [a]2D6 =À13.08 (c=1.0
in CHCl3); lit.[5a] [a]D25 =+128 (c=1.0 in CHCl3), 84% ee for R. NMR
spectra were consistent with previously reported data.[4,5a]
Ethyl (S)-3,7-dimethyloct-6-enoate (35): Yield: 96% (190.2 mg,
0.96 mmol), colorless oil. Chiral GC analysis: Alltech CHIRALDEX G-
TA, Rt =75.9 min (minor), 78.5 min (major), 92% ee for S; [a]2D8 =À3.828
(c=1.0 in CHCl3); lit.[5a] [a]D25 =+4.68 (c=1.1 in CHCl3), 86% ee for R.
NMR spectra were consistent with previously reported data.[4,5a]
X-ray crystallographic determination: Single crystals suitable for X-ray
analysis were obtained by recrystallization from diethyl ether/hexane at
room temperature. A crystal was mounted on a quartz fiber, and diffrac-
tion data were collected in q ranges at 173 K with a Brucker SMART
APEX CCD diffractometer with graphite-monochromated MoKa radia-
tion (l=0.71073 Š). An empirical absorption correction was applied by
using SADABS. The structure was solved by direct methods and refined
by full-matrix least-squares on F2 by using SHELXTL.[28] All non-hydro-
gen atoms were refined with anisotropic displacement parameters. Re-
finement details: empirical formula; C22H31N2O7Rh; Mr =538.40; crystal
system: monoclinic; space group: P21; a=8.7699(5), b=15.5207(9), c=
9.5423(6) Š, a=908, b=115.5730(10)8, g=908, V=1171.61(12) Š3, Z=2,
1calcd =1.526 MgmÀ3, m=0.773 mmÀ1, F(000)=556, crystal size=0.1”0.3”
0.5 mm3, q range=2.37–29.158; index ranges: À12ꢀhꢀ11, À19ꢀkꢀ21,
À8ꢀlꢀ13; reflections collected 9075, independent reflections 5490 [R-
(int)=0.0181]; completeness q=29.158, 98.9%; max/min transmission
1.000000/0.811634; data/restraints/parameters 5490/1/300; goodness-of-fit
on F2 1.085; final R indices [I>2s(I)]: R1=0.0206, wR2=0.0557;R indi-
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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology,
Japan (Reaction Control of Dynamic Complexes, No. 420). H.N. also
thanks the DAIKO Foundation for financial support.
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Received: July 19, 2005
Published online: September 29, 2005
Chem. Eur. J. 2006, 12, 63 – 71
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
71