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Synlett 2009(4): 667-670  
DOI: 10.1055/s-0028-1087811
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© Georg Thieme Verlag Stuttgart ˙ New York

Guanidine-Urea Bifunctional Organocatalyst for Asymmetric Epoxidation of 1,3-Diarylenones with Hydrogen Peroxide

Shinji Tanaka, 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;
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Publication History

Received 22 September 2008
Publication Date:
16 February 2009 (online)

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Abstract

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.

Key words

guanidine - urea - hydrogen peroxide - epoxidation - electron-deficient olefin

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Synthesis of Catalyst 1a and Spectral Data for 1a-e
To a solution of guanidine (S,S)-1f ¹0a (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: [α]D ²4 -41.2 (c 1.3, CHCl3). ¹H NMR (400 MHz, CD3OD): δ = 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): δ = 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.
Compound 1b: [α]D ²5 -11.3 (c 1.1, CHCl3). ¹H NMR (400 MHz, CD3OD): δ = 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): δ = 157.82, 156.31, 142.99, 138.79, 133.13 (q, J CF = 32.6 Hz), 130.14, 129.66, 127.81, 124.76 (d, J CF = 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: [α]D ²6 -24.5 (c 1.4, CHCl3). ¹H NMR (400 MHz, CD3OD): δ = 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): δ = 164.61 (dd, J CF = 15.3, 243.4 Hz), 157.77, 156.22, 143.55 (t, J CF = 13.5 Hz), 138.81, 130.18, 129.64, 127.77, 102.09 (dd, J CF = 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: [α]D ²5 -40.4 (c 1.1, CHCl3). ¹H NMR (400 MHz, CD3OD): δ = 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): δ = 158.30, 156.31, 143.15, 133.20 (q, J CF = 32.6 Hz), 128.84, 124.78 (d, J CF = 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.
Compound 1e: [α]D ²6 -8.9 (c 1.1, CHCl3). ¹H NMR (400 MHz, CD3OD): δ = 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): δ = 157.80, 156.25, 143.11, 133.15 (q, J CF = 32.6 Hz), 128.84, 124.79 (d, J CF = 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.

Scheme 1

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.

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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
[α]D ²4 -210.1 (c 0.83, CHCl3). ¹H NMR (400 MHz, CDCl3): δ = 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 (ϕ) × 25 cm (L), hexane-2-PrOH = 98:2, 1.00 mL/min, t R(minor) = 19.5 min (2S,3R); t R(major) = 20.4 min (2R,3S).¹7a

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.