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