Guanidine-urea bifunctional organocatalyst for asymmetric epoxidation of 1,3-diarylenones with hydrogen peroxide

Article abstract of DOI:10.1055/s-0028-1087811

A highly enantioselective catalytic epoxidation reaction to the electron-deficient α,β-unsaturated olefin moieties of diarylenones was achieved with high chemical yield by using aqueous hydrogen peroxide in the presence of a newly developed guanidine-urea bifunctional organocatalyst. These functional groups were suggested to perform cooperatively by interacting with guanidine-hydrogen peroxide and urea-enones, respectively. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087811

CLUSTER
667
Guanidine-Urea Bifunctional Organocatalyst for Asymmetric Epoxidation of
1,3-Diarylenones with Hydrogen Peroxide
Bifunctional
O
h
rganocatalys
i
t
for
A
n
symmetric
E
j
poxida
i
tion of 1, 3-D
T
s
anaka, Kazuo Nagasawa*
Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Fax +81(42)3887295; E-mail: knaga@cc.tuat.ac.jp
Received 22 September 2008
work on hetero-bifunctional organocatalysts,10 we envis-
Abstract: A highly enantioselective catalytic epoxidation reaction
aged that a guanidine-urea conjugated catalyst would co-
to the electron-deficient a,b-unsaturated olefin moieties of diaryl-
operatively promote the asymmetric epoxidation with
enones was achieved with high chemical yield by using aqueous hy-
aqueous hydrogen peroxide of electron-deficient a,b-
drogen peroxide in the presence of a newly developed guanidine-
urea bifunctional organocatalyst. These functional groups were sug- unsaturated carbonyl olefins through the interactions of
type I, that is, urea–carbonyl group11 and hydrogen perox-
gested to perform cooperatively by interacting with guanidine–
hydrogen peroxide and urea-enones, respectively.
ide–guanidine group interactions, or type II, that is, guani-
dine–carbonyl group12 and hydrogen peroxide–urea
Key words: guanidine, urea, hydrogen peroxide, epoxidation, elec-
group13 interactions (Figure 1).
tron-deficient olefin
R
NH
Enantioselective catalytic epoxidation of electron-defi-
*
cient olefins is a powerful method for the preparation of
useful chiral building blocks.1 In the past few decades, a
number of efficient methods involving chiral metal and/or
metal-free catalysts with various oxidants have been de-
veloped.2 Among them, the use of aqueous hydrogen per-
oxide as the oxidant has great advantages: it is
environmentally friendly, low in cost, safe to handle and
provides high atom-efficiency.3 Since Juliá and Colonna
reported the first application of hydrogen peroxide for
asymmetric epoxidation,4 many efforts have been devoted
to the development of organocatalysts.5 Nevertheless,
only a few efficient methods have been reported so far. A
sterically hindered pyrrolidine organocatalyst was
successfully applied to the asymmetric epoxidation to
a,b-unsaturated aldehydes with hydrogen peroxide by
Jørgensen et al.6 In the case of a,b-unsaturated ketones,
cinchona alkaloid derivatives were reported to catalyze
the epoxidation with hydrogen peroxide. Jew et al. report-
ed a highly enantioselective version of this reaction using
a dimerized cinchona alkaloid catalyst.7 Recently, a chiral
primary amine salt was reported for the highly asymmet-
ric epoxidation to cyclic enones by List et al.8
chiral
N
H
N
H
O
O
spacer
N
H
N
H
O
O
H
R1
R2
type I
R
NH
*
chiral
spacer
N
H
N
H
O
N
H
N
H
O
R2
R1
O
O
H
type II
Figure 1 Cooperative interactions of guanidine-urea bifunctional
catalyst 1 with enone and hydrogen peroxide
Herein, we describe the highly enantioselective epoxida-
tion of electron-deficient a,b-unsaturated olefins of 1,3-
diarylenones with hydrogen peroxide in the presence of a
guanidine-urea bifunctional phase-transfer catalyst under
mild reaction conditions.
Guanidine catalysts have also been explored for nucleo-
philic asymmetric epoxidation.9 In these reactions, hydro-
gen peroxide can be used as an oxidant, but
enantioselectivity is moderate or poor. We have recently
reported a guanidine-hydroxy bifunctional organocatalyst
for the asymmetric epoxidation of 1,3-diarylenones.9h
This catalyst, however, only promoted the reaction with
tert-butyl hydroperoxide as an oxidant, giving epoxides
with moderate enantioselectivity. As a continuation of our
We have synthesized guanidine-urea organocatalysts 1 in
which the functional groups are connected with chiral
spacers derived from amino acids.14 With the requirement
of a biphasic reaction system because of the use of aque-
ous hydrogen peroxide, we introduce a long alkyl chain on
the guanidine group.10d Since the interaction of the urea
group with reaction substrates was expected to be one of
the key features, catalysts having electron-withdrawing
SYNLETT 2009, No. 4, pp 0667–0670
x
x.
x
x.
2
0
0
9
Advanced online publication: 16.02.2009
DOI: 10.1055/s-0028-1087811; Art ID: Y00908ST
© Georg Thieme Verlag Stuttgart · New York

668
S. Tanaka, K. Nagasawa
CLUSTER
Table 1 Asymmetric Epoxidation of trans-Chalcone Catalyzed by
1–3
groups on the aromatic ring were also synthesized (1a–
c).15
1 or 2 or 3 (5 mol%)
30% H2O2 aq (5 equiv)
NaOH (50 mol%)
Initial screening was conducted using the reaction of
trans-chalcone (4a) with 30% aqueous hydrogen peroxide
(5 equiv) and NaOH (50 mol%) in the presence of 5 mol%
of 1 in organic solvents–H2O (1:1 by volume) at 0 °C. As
shown in Table 1, catalysts 1a–e (Figure 2) all promoted
the epoxidation reaction quantitatively (entries 1–5).
O
O
O
Ph
Ph
Ph
Ph
organic solvent/H2O (1:1)
0 °C, 24 h
4a
(2R,3S)-5a
Entry
Catalyst
1a
Organic solvent Yield (%)a ee (%)b,c
C18H37
1
2
toluene
toluene
toluene
toluene
toluene
hexane
CH2Cl2
Et2O
99
99
99
99
99
99
99
99
99
99
99
99
73
45
0
15
78
22
24
20
48
44
25
14
4
Cl–
NH
1b
1c
H
H
H
H
N
N
N
N
S
R
S
R
Ar
N
H
N
Ar
3
H
O
O
4
1d
1e
(S,S)-1
1a: R = Bn, Ar = Ph
1b: R = Bn, Ar = 3,5-(CF3)2C6H3
1c: R = Bn, Ar = 3,5-(F)2C6H3
1d: R = i-Pr, Ar = 3,5-(CF3)2C6H3
1e: R = Me, Ar = 3,5-(CF3)2C6H3
5
6
1b
1b
1b
1b
1b
1b
1b
1b
1b
2
7
CF3
CF3
8
C18H37
NH
9
THF
F3C
N
H
N
H
CF3
10
11d
12e
13f
14f
15
16
MeOH
toluene
toluene
toluene
CH2Cl2
toluene
toluene
Cl–
CF3
2
90
94
21
19
–
CF3
O
F3C
N
H
N
H
CF3
3
Figure 2 Structures of guanidine-urea bifunctional catalyst 1, gua-
nidine 2, and urea 3
3
0
–
a Isolated yield.
b Enantiomeric excess was determined by HPLC using a chiral col-
The enantioselectivity varied according to the substituents
on the Ar groups and chiral spacers in 1. The introduction
of 3,5-bistrifluoromethyl groups on the phenyl moiety
was effective in improving the enantioselectivity (entries
1–3). Among the catalysts 1b,d,e, the phenylalanine-
derived chiral spacer of 1b gave the highest enantioselec-
tivity of 78% ee (entries 2 vs. 4 and 5). Next, the solvents
in the biphasic system and their ratios were optimized (en-
tries 6–10). Toluene was found to be the best solvent.
When the volume ratio of H2O was decreased to 1:19,
enantioselectivity was increased to 90% ee (entry 11).
Finally, 5a was quantitatively obtained with 94% ee by
lowering the temperature to –10 °C (entry 12). In this re-
action, catalyst 1b was quantitatively recovered from the
reaction mixture by simple silica gel column chromatog-
raphy, and could be reused without any loss of either cat-
alytic activity or enantioselectivity.16 Under these reaction
conditions, tert-butyl hydroperoxide was not effective as
an oxidant (entries 13 and 14), which presumably inter-
acts poorly with catalyst because of steric hindrance.
Since the catalyst 211a and 3,11a,b lacking the urea group or
guanidine group, did not promote the reaction at all under
these conditions, the guanidine and urea groups were
umn.
c The absolute configuration was determined by comparison of the
HPLC retention time with the literature data.
d Toluene/H2O = 19:1 (v/v).
e Toluene/H2O = 19:1 (v/v), –10 °C. Reaction was completed within
6 h.
f tert-Butyl hydroperoxide in decane (5 equiv) was used as the oxi-
dant.
revealed to act cooperatively in this asymmetric epoxida-
tion reaction (entries 15 and 16).
With the optimized reaction conditions in hand (Table 1,
entry 12), the substrate scope of this epoxidation reaction
was investigated. As shown in Table 2, a variety of 1,3-di-
arylenones, having electron-withdrawing and/or donating
groups, could be applied under the present reaction condi-
tions. That is, epoxidation of 4b–j proceeded smoothly
within 3–20 hours, and gave the corresponding epoxy
ketones 5b–j in quantitative yield with high enantioselec-
tivity.18,19
1
To clarify the roles of functional groups in 1b, H NMR
studies were employed using 4a with 2 and 3. As a result,
Synlett 2009, No. 4, 667–670 © Thieme Stuttgart · New York

CLUSTER
Bifunctional Organocatalyst for Asymmetric Epoxidation of 1,3-Diarylenones
669
Shibasaki, M. J. Synth. Org. Chem. Jpn. 2002, 60, 94.
(c) Lauret, C.; Roberts, S. M. Aldrichimica Acta 2002, 35,
47.
Table 2 Asymmetric Epoxidation of 1,3-Diarylenones Catalyzed
by 1b under Optimized Conditions
1b (5 mol%)
(3) (a) Noyori, R.; Aoki, M.; Sato, K. Chem. Commun. 2003,
1977. (b) Campos-Martin, J. M.; Blanco-Brieva, G.; Fierro,
J. L. G. Angew. Chem. Int. Ed. 2006, 45, 6962; and
references cited therein.
(4) (a) Juliá, S.; Masana, J.; Vega, J. C. Angew. Chem., Int. Ed.
Engl. 1980, 19, 929. (b) Juliá, S.; Guixer, J.; Masana, J.;
Rocas, J.; Colonna, S.; Annuziata, R.; Molinari, H. J. Chem.
Soc., Perkin Trans. 1 1982, 1317.
30% H2O2 aq (5 equiv)
NaOH (50 mol%)
O
O
O
R2
R1
R2
R1
toluene/H2O (19:1)
–10 °C
4
(2R,3S)-5
Entry 4
R1
R2
Time Yield
(h)
ee
(%)a
(%)b,c
(5) (a) Arai, S.; Tsuge, H.; Shioiri, T. Tetrahedron Lett. 1998,
39, 7563. (b) Arai, S.; Tsuge, H.; Oku, M.; Miura, M.;
Shioiri, T. Tetrahedron 2002, 58, 1623. (c) Dehmlow, E.
V.; Düttmann, S.; Neumann, B.; Stammler, H.-G. Eur. J.
Org. Chem. 2002, 2087. (d) Berkessel, A.; Gasch, N.;
Glaubiz, K.; Koch, C. Org. Lett. 2001, 3, 3839. (e) Kelly,
D. R.; Roberts, S. M. Biopolymers 2006, 84, 74.
(f) Berkessel, A.; Koch, B.; Toniolo, C.; Rainaldi, M.;
Broxterman, Q. B.; Kaptein, B. Biopolymers 2006, 84, 90.
(g) Geller, T.; Gerlach, A.; Krüger, C. M.; Militzer, H.-C.
Tetrahedron Lett. 2004, 45, 5065. (h) Geller, T.; Krüger,
C. M.; Militzer, H.-C. Tetrahedron Lett. 2004, 45, 5069.
(i) Yi, H.; Zou, G.; Li, Q.; Chen, Q.; Tang, J.; He, M.-y.
Tetrahedron Lett. 2005, 46, 5665. (j) Hori, K.; Tamura, M.;
Tani, K.; Nishiwaki, N.; Ariga, M.; Tohda, Y. Tetrahedron
Lett. 2006, 47, 3115. (k) Sundén, H.; Ibrahem, I.; Córdova,
A. Tetrahedron Lett. 2006, 47, 99. (l) Zhao, G.-L.; Ibrahem,
I.; Sundén, H.; Córdova, A. Adv. Synth. Catal. 2006, 349,
1210.
1
2
3
4
5
6
7
8d
9
4b
Ph
Ph
Ph
Ph
Ph
4-MeC6H4
4-ClC6H4
4
99 5b
99 5c
99 5d
99 5e
98 5f
99 5g
99 5h
91 5i
98 5j
91
90
85
96
96
90
90
86
92
4c
4d
4e
4f
4
4-O2NC6H4 11
1-naphthyl
2-naphthyl
Ph
6
18
3
4g
4h
4i
4-BrC6H4
4-MeOC6H4
2-furyl
Ph
7
Ph
20
12
4j
4-ClC6H4
4-MeC6H4
a Isolated yield.
b Enantiomeric excess was determined by HPLC using a chiral col-
umn.
(6) Marigo, M.; Franzén, J.; Poulsen, T. B.; Zhuang, W.;
Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 6964.
(7) Jew, S.-s.; Lee, J. H.; Jeong, B.-S.; Yoo, M.-S.; Kim, M.-J.;
Lee, J.; Choi, S.-h.; Lee, K.; Lah, M. S.; Park, H.-g. Angew.
Chem. Int. Ed. 2005, 44, 1383.
c The absolute configuration was determined by comparison of the
HPLC retention time with the literature data.17
d Reaction was carried out at –20 °C.
(8) Wang, X.; Reisinger, C. M.; List, B. J. Am. Chem. Soc. 2008,
130, 6070.
a downfield shift of NH in 3 was observed from d = 5.95
to 8.21 ppm in the case of mixture with 4a.20,21 These ob-
servations suggest the type-I interactions are plausible for
the asymmetric epoxidation with 1b.
(9) (a) Ishikawa, T.; Isobe, T. Chem. Eur. J. 2002, 8, 552.
(b) McManus, J. C.; Carey, J. S.; Taylor, R. J. K. Synlett
2003, 365. (c) McManus, J. C.; Genski, T.; Carey, J. S.;
Taylor, R. J. K. Synlett 2003, 369. (d) Allingham, M. T.;
Howard-Jones, A.; Murphy, P. J.; Thomas, D. A.; Caulkett,
P. W. R. Tetrahedron Lett. 2003, 44, 8677. (e) Kumamoto,
T.; Ebine, K.; Endo, M.; Araki, Y.; Fushimi, Y.; Miyamoto,
I.; Ishikawa, T.; Isobe, T.; Fukuda, K. Heterocycles 2005,
66, 347. (f) Ishikawa, T.; Kumamoto, T. Synthesis 2006,
737. (g) Kita, T.; Shin, B.; Hashimoto, Y.; Nagasawa, K.
Heterocycles 2007, 73, 241. (h) Shin, B.; Tanaka, S.; Kita,
T.; Hashimoto, Y.; Nagasawa, K. Heterocycles 2008, 76,
801. (i) Terada, M.; Nakano, M. Heterocycles 2008, 1049.
(10) (a) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Adv. Synth.
Catal. 2005, 347, 1643. (b) Sohtome, Y.; Takemura, N.;
Iguchi, T.; Hashimoto, Y.; Nagasawa, K. Synlett 2006, 144.
(c) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Eur. J. Org.
Chem. 2006, 2894. (d) Sohtome, Y.; Takemura, N.; Takada,
K.; Takagi, R.; Iguchi, T.; Nagasawa, K. Chem. Asian J.
2007, 2, 1150. (e) Takada, K.; Takemura, N.; Cho, K.;
Sohtome, Y.; Nagasawa, K. Tetrahedron Lett. 2008, 49,
1623.
In summary, asymmetric epoxidation reaction at the elec-
tron-deficient a,b-unsaturated olefins of 1,3-diarylenones
was achieved by using aqueous hydrogen peroxide in the
presence of a guanidine-urea bifunctional organocatalyst,
with high chemical yield and enantioselectivity under bi-
phasic conditions.
Acknowledgment
This research was supported in part by grants from the Uehara
Memorial Foundation and the Nagase Science and Technology
Foundation.
References and Notes
(1) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
John Wiley and Sons: New York, 1994. (b) Comprehensive
Asymmetric Catalysis; Jacobsen, E. N.; Pfaltz, A.;
Yamamoto, H., Eds.; Springer: New York, 1999.
(c) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.;
Wiley: New York, 2000. (d) Lauret, C. Tetrahedron:
Asymmetry 2001, 12, 2359.
(11) (a) Sohtome, Y.; Tanatani, A.; Hashimoto, Y.; Nagasawa, K.
Chem. Pharm. Bull. 2004, 52, 477. (b) Sohtome, Y.;
Tanatani, A.; Hashimoto, Y.; Nagasawa, K. Tetrahedron
Lett. 2004, 45, 5589. (c) Maher, D. J.; Connon, S. J.
Tetrahedron Lett. 2004, 45, 1301.
(12) Howard-Jones, A.; Murphy, P. J.; Thomas, D. A. J. Org.
(2) For reviews, see: (a) Porter, M. J.; Skidmore, J. Chem.
Commun. 2000, 1215. (b) Nemoto, T.; Ohoshima, T.;
Chem. 1999, 64, 1039.
Synlett 2009, No. 4, 667–670 © Thieme Stuttgart · New York

670
S. Tanaka, K. Nagasawa
CLUSTER
(13) (a) Lu, C.-S.; Hughes, E. W.; Giguère, P. A. J. Am. Chem.
Soc. 1941, 63, 1507. (b) Aida, K. J. Inorg. Nucl. Chem.
1963, 25, 165. (c) Cooper, M.; Heaney, H.; Newbold, A. J.;
Sanderson, W. R. Synlett 1990, 533. (d) Heaney, H.
Aldrichimica Acta 1993, 26, 35.
Compound 1e: [a]D26 –8.9 (c 1.1, CHCl3). 1H NMR (400
MHz, CD3OD): d = 8.04 (s, 4 H), 7.46 (s, 2 H), 3.91 (br s, 2
H), 3.41–3.14 (m, 6 H), 1.64 (m, 2 H), 1.29 (d, J = 6.9 Hz, 6
H), 1.27–1.10 (m, 30 H), 0.87 (t, J = 6.9 Hz, 3 H). 13C NMR
(100 MHz, CD3OD): d = 157.80, 156.25, 143.11, 133.15 (q,
JCF = 32.6 Hz), 128.84, 124.79 (d, JCF = 272.2 Hz), 120.73,
119.00, 115.72, 47.05 (br), 43.13, 33.08, 30.75 (br), 30.70,
30.61, 30.52, 30.48, 30.14, 29.63, 27.90, 23.74, 18.34,
14.46. ESI-HRMS: m/z calcd for C43H62F12N7O2 [M + H+]:
936.4773; found: 936.4734.
(14) Synthesis of Catalyst 1a and Spectral Data for 1a–e
To a solution of guanidine (S,S)-1f10a (258 mg, 0.317 mmol)
in CH2Cl2 (3.0 mL) was added TFA (3.0 mL) at 0 °C. The
reaction mixture was warmed to r.t. and stirred for 2 h. The
resulting mixture was concentrated in vacuo to give diamine.
To a solution of the diamine in THF (6.0 mL) was added
phenyl isocyanate (0.21 mL, 1.90 mmol), and the mixture
was stirred for 12 h. The resulting mixture was concentrated
in vacuo, and the residue was purified by flash column
chromatography on silica gel (n-hexane–EtOAc = 4:1 to 1:1,
CHCl3–MeOH = 9:1) to give 1a as a TFA salt (Scheme 1).
The counteranion of 1a was exchanged into Cl– by treatment
with sat. aq NH4Cl and EtOAc solution, and gave 1a as a
HCl form in 81% yield from 1f (219 mg, 0.257 mmol).
Compound 1a: [a]D24 –41.2 (c 1.3, CHCl3). 1H NMR (400
MHz, CD3OD): d = 7.33–7.10 (m, 18 H), 6.93 (t, J = 7.4 Hz,
2 H), 4.11 (br s, 2 H), 3.45–3.32 (m, 4 H), 3.16 (t, J = 7.3 Hz,
2 H), 3.03 (dd, J = 4.5, 14.1 Hz, 2 H), 2.79 (dd, J = 9.6, 13.7
Hz, 2 H), 1.59 (m, 2 H), 1.34–1.14 (m, 30 H), 0.88 (t, J = 7.3
Hz, 3 H). 13C NMR (100 MHz, CD3OD): d = 158.51, 156.33,
140.52, 138.97, 130.22, 129.83, 129.68, 127.78, 123.67,
120.18, 52.46 (br), 47.63 (br), 43.12, 39.32, 33.09, 30.78
(br), 30.69, 30.66, 30.49, 30.39, 29.75, 27.99, 23.75, 14.48.
ESI-HRMS: m/z calcd for C51H74N7O2 [M + H+]: 816.5904;
found: 816.5895.
C18H37
Cl–
NH
1. TFA
BocHN
NHBoc
S
S
(S,S)-1a
N
N
2. PhNCO
H
H
Bn
Bn
(S,S)-1f
Scheme 1
(15) (a) Schreiner, P. R.; Wittkopp, A. Org. Lett. 2002, 4, 217.
(b) Wittkopp, A.; Schreiner, P. R. Chem. Eur. J. 2003, 9,
407.
(16) We recycled the catalyst 1b five times under the conditions
of entry 11 in Table 1. In these reactions, the yields and
enantioselectivities were as follows: 2nd run: 95% with 90%
ee; 3rd run: 99% with 90% ee; 4th run: 99% with 91% ee;
and 5th run: 99% with 89% ee.
(17) (a) Lattanzi, A. Org. Lett. 2005, 7, 2579. (b) Li, Y.; Liu, X.;
Yang, Y.; Zhao, G. J. Org. Chem. 2007, 72, 288. (c) Ye, J.;
Wang, Y.; Chen, J.; Liang, X. Adv. Synth. Catal. 2004, 346,
691. (d) Kumaraswamy, G.; Sastry, M. N. V.; Jena, N.;
Kumarb, K. R.; Vairamanic, M. Tetrahedron: Asymmetry
2003, 14, 3797. (e) Ooi, T.; Ohara, D.; Tamura, M.;
Maruoka, K. J. Am. Chem. Soc. 2004, 126, 6844.
(18) Typical Procedure for Asymmetric Epoxidation of 4a
A mixture of enone 4a (20.8 mg, 0.10 mmol) and guanidine-
urea organocatalyst (S,S)-1b (5.6 mg, 0.005 mmol, 5 mol%)
in toluene (0.95 mL) was cooled at –10 °C. To the mixture
was added 1 M aq NaOH (0.050 mL, 0.050 mmol) and 30%
aq H2O2 (0.051 mL, 0.50 mmol of H2O2). The mixture was
stirred vigorously at –10 °C under argon atmosphere for 6 h.
To the reaction mixture was added sat. aq NH4Cl, and the
organic layer was extracted with EtOAc. The combined
organic extracts were dried over MgSO4, filtered, and
concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel (n-hexane–EtOAc =
100:1 to 10:1) to give epoxy ketone 5a (22.3 mg, 99%) and
catalyst 1b was quantitatively recovered (5.6 mg, >99%).
The ee and absolute configuration of the epoxy ketone 5a
was determined by HPLC using a chiral column.
Spectral Data and HPLC Data for Epoxy Ketone 5a
[a]D24 –210.1 (c 0.83, CHCl3). 1H NMR (400 MHz, CDCl3):
d = 8.02 (d, J = 6.9 Hz, 2 H), 7.63 (t, J = 7.8 Hz, 1 H), 7.49
(t, J = 7.8 Hz, 2 H), 7.45–7.35 (m, 5 H), 4.31 (d, J = 1.8 Hz,
1 H), 4.08 (d, J = 1.8 Hz, 1 H). HPLC separation conditions:
Chiralcel OD-H, 0.46 cm (f) × 25 cm (L), hexane–2-PrOH =
98:2, 1.00 mL/min, tR(minor) = 19.5 min (2S,3R);
tR(major) = 20.4 min (2R,3S).17a
Compound 1b: [a]D25 –11.3 (c 1.1, CHCl3). 1H NMR (400
MHz, CD3OD): d = 7.94 (s, 4 H), 7.44 (s, 2 H), 7.31–7.14
(m, 10 H), 4.14 (br s, 2 H), 3.41 (d, J = 5.0 Hz, 4 H), 3.18 (t,
J = 7.3 Hz, 2 H), 3.07 (dd, J = 4.0, 13.9 Hz, 2 H), 2.80 (dd,
J = 9.5, 13.9 Hz, 2 H), 1.61 (m, 2 H), 1.34–1.08 (m, 30 H),
0.88 (t, J = 6.9 Hz, 3 H). 13C NMR (100 MHz, CD3OD): d =
157.82, 156.31, 142.99, 138.79, 133.13 (q, JCF = 32.6 Hz),
130.14, 129.66, 127.81, 124.76 (d, JCF = 271.3 Hz), 120.70,
118.98, 115.79, 52.66 (br) 47.46, 43.10, 39.20, 33.08, 30.75
(br), 30.61, 30.54, 30.47, 30.16, 29.64, 27.92, 23.74, 14.46.
ESI-HRMS: m/z calcd for C55H70F12N7O2 [M + H+]:
1088.5399; found: 1088.5370.
Compound 1c: [a]D26 –24.5 (c 1.4, CHCl3). 1H NMR (400
MHz, CD3OD): d = 7.32–7.17 (m, 10 H), 6.97 (d, J = 9.6 Hz,
4 H), 6.46 (t, J = 9.2 Hz, 2 H), 4.10 (br s, 2 H), 3.39 (d,
J = 5.5 Hz, 4 H), 3.18 (t, J = 7.3 Hz, 2 H), 3.07 (dd, J = 4.6,
13.8 Hz, 2 H), 2.79 (dd, J = 9.6, 14.2 Hz, 2 H), 1.63 (m, 2 H),
1.35–1.07 (m, 30 H), 0.88 (t, J = 6.4 Hz, 3 H). 13C NMR (100
MHz, CD3OD): d = 164.61 (dd, JCF = 15.3, 243.4 Hz),
157.77, 156.22, 143.55 (t, JCF = 13.5 Hz), 138.81, 130.18,
129.64, 127.77, 102.09 (dd, JCF = 8.6, 21.1 Hz), 52.54 (br),
47.49 (br), 43.16, 39.22, 33.07, 30.78 (br), 30.71, 30.65,
30.48, 30.38, 29.76, 28.03, 23.74, 14.50. ESI-HRMS: m/z
calcd for C51H70F4N7O2 [M + H+]: 888.5527; found:
888.5572.
Compound 1d: [a]D25 –40.4 (c 1.1, CHCl3). 1H NMR (400
MHz, CD3OD): d = 8.04 (s, 4 H), 7.47 (s, 2 H), 3.78 (br s, 2
H), 3.42 (dd, J = 13.8, 5.1 Hz, 2 H), 3.25 (m, 2 H), 3.17 (t,
J = 7.4 Hz, 2 H), 1.94 (br, 2 H), 1.58 (m, 2 H), 1.33–1.08 (m,
30 H), 1.03 (d, J = 6.4 Hz, 6 H), 1.01 (d, J = 6.4 Hz, 6 H),
0.88 (t, J = 6.9 Hz, 3 H). 13C NMR (100 MHz, CD3OD): d =
158.30, 156.31, 143.15, 133.20 (q, JCF = 32.6 Hz), 128.84,
124.78 (d, JCF = 272.2 Hz), 120.73, 118.84, 115.68, 55.92
(br), 46.04, 43.03, 33.08, 31.04 (br), 30.75 (br), 30.70, 30.62,
30.52, 30.48, 30.19, 29.80, 27.87, 23.74, 20.19, 17.62 14.46.
ESI-HRMS: m/z calcd for C47H70F12N7O2 [M + H+]:
992.5399; found: 992.5373.
(19) In the case of aliphatic substituted enones, enantioselec-
tivities were moderate to low (ex. R1 = Me, R2 = Ph, 99%
yield with 41% ee).
(20) NMR studies were performed in C6D6.
(21) Sohtome, Y.; Takemura, N.; Takagi, R.; Hashimoto, Y.;
Nagasawa, K. Tetrahedron 2008, 64, 9423; and references
cited therein.
Synlett 2009, No. 4, 667–670 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.