Annulation of 3-[(R)-p-Toluenesulfinyl]-2-oxopropylidenetriphenyl-phosphorane with 1,4-Enediones; Highly Enantioselective Synthesis of Cyclopentenones

Abstract

3-[(R)-p-Toluenesulfinyl]-2-oxopropylidenetriphenyl-phosphorane reacted with 1,4-enediones in the presence of BuLi to give (4S,5R)-4-acylmethyl-5-[(R)-p-toluenesulfinylcyclopent-2-enones in a highly diastereoselective fashion. Subsequent desulfurization of the cyclization products furnished highly enantiomerically enriched (S)-4-acylmethylcyclopent-2-enones.

Key words

chiral sulfoxide - cyclopentenone - cyclization - dia­stereoselective Michael addition - phosphorane

References

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1

New address: K. Matsumoto, Department of Chemistry, College of Science and Engineering, Meisei University, Hodokubo, Hino, Tokyo 191-8506, Japan.

2

Faculty of Pharmaceutical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.

10

Typical Procedure; Preparation of (4 S ,5 R )-4-(2-Oxo-2-phenylethyl)-5-[( R )- p -toluenesulfinyl]cyclopent-2-enone(5a). To a solution of 2 (159 mg, 0.5 mmol) in THF (5 mL) was added a 1.56 M BuLi-hexane solution (0.39 mL, 0.6 mmol) at -78 °C and the mixture was stirred for 30 min at that temperature. To the mixture was added a solution of 3 (73 mg, 0.25 mmol) in THF (3 mL) and stirring was continued for 1 h at -78 °C. To this reaction mixture was successively added TMEDA (75 µL, 0.5 mmol), a solution of CuCN (45 mg, 0.5 mmol) and LiCl (43 mg, 1.0 mmol) in THF (3 mL) and then a solution of 4a (58 mg, 0.25 mmol) in THF (3 mL). After being stirred for 1 h at -78 °C, the reaction mixture was treated with acetic acid (29 µL, 0.5 mmol) and sat. aq NaHCO₃ (1 mL) and then stirred for 12 h at r.t. The reaction mixture was poured into brine and extracted with EtOAc. The extract was dried and evaporated in vacuo. The residue was purified by flash chromatography (hexane-EtOAc, 2:1) to give 5a (55 mg, 53%) as colorless needles; mp 147-148 °C (hexane-EtOAc). Spectroscopic data of 5a: ¹H NMR (500 MHz, CDCl₃): δ = 2.35 (s, 3 H), 3.19 (dd, 1 H, J = 18.0, 8.9 Hz), 3.53 (dd, 1 H, J = 18.0, 8.9 Hz), 3.88 (s, 1 H), 4.43 (m, 1 H), 6.32 (s, 1 H), 7.26 (bt, 2 H, J = 8.8 Hz), 7.43 (m, 3 H), 7.44 (d, 2 H, J = 7.9 Hz), 7.50 (m, 2 H), 7.53 (d, 2 H, J = 7.9 Hz), 7.58 (br t, 1 H, J = 8.8 Hz), 7.84 (br d, 2 H, J = 8.8 Hz).
¹³C NMR (125 MHz, CDCl₃): δ = 198.34, 197.28, 176.23, 141.86, 136.61, 136.17, 133.64, 132.34, 131.46, 129.55, 129.37, 129.17, 128.71, 128.02, 127.14, 124.81, 72.41, 41.75, 38.36, 21.44. IR (Nujol): ν = 1686, 1596, 1572, 1180, 1046, 732, 690 cm^-1. FABMS: m/z (%) = 415(6) [M⁺ + 1]. Anal. Calcd for C₂₆H₂₂O₃S: H, 5.35; C, 75.34. Found: H, 5.22; C, 75.03.

11

Crystal Data: C₂₆H₂₂O₃S, M = 414.52, triclinic, space group P-1 (#2), Z = 2, a = 10.213(1) Å, b = 13.043(1) Å, c = 8.9152(6) Å, α = 102.298(8)°, β = 101.744(8)°, γ = 67.742(8)°, V = 1063.9(2) ų, Dc = 1.294 g/cm³, F(000) = 436, µ (Cu K_α) = 15.05 cm^-, T = 296 K, colorless prism, crystal size = 0.1 × 0.1 × 0.1 mm, 3373 measured reflections, 2203 reflections with I > 3σ(I) by Rigaku AFC-5R diffractometer, R = 0.043, Rw = 0.049, 359 parameters. Full information on the crystal structure can be ordered from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:[phone]; e-mail: [e-mail] or http://www.ccdc.ac.uk), upon request, quoting the deposition number CCDC 185027.

12

8a: Mp 47-48 °C (hexane-EtOAc). ¹H NMR (500 MHz, CDCl₃): δ = 1.96 (s, 3 H), 2.39 (s, 3 H), 3.22 (dd, 1 H, J = 17.7, 6.4 Hz), 3.52 (dd, 1 H, J = 17.7, 5.2 Hz), 3.68 (m, 1 H), 3.90 (d, 1 H, J = 2.1 Hz), 5.79 (s, 1 H), 7.28 (d, 2 H, J = 7.9 Hz), 7.48 (d, 2 H, J = 7.9 Hz), 7.50 (br t, 2 H, J = 8.3 Hz), 7.61 (br t, 1 H, J = 8.3 Hz), 7.95 (br d, 2 H, J = 8.3 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 198.96, 197.32, 179.83, 141.91, 136.19, 133.76, 131.51, 129.59, 129.18, 128.85, 128.10, 125.01, 71.99, 40.93, 40.43, 21.47, 17.64. IR (Nujol): ν = 1680, 1628, 1602, 752, 722 cm^-1. EIMS: m/z (%) = 336(61) [M⁺ - 16], 231(9), 216(95), 213(69), 105(100), 77(86). HRMS (EI): Calcd for C₂₁H₂₀O₃S: 352.1133. Found: 352.1102. 9a: Oil. ¹H NMR (500 MHz, CDCl₃): δ = 2.11 (s, 3 H), 2.34 (s, 3 H), 2.60 (dd, 1 H, J = 17.7, 8.9 Hz), 2.98 (dd, 1 H, J = 17.7, 3.4 Hz), 3.48 (m, 1 H), 3.89 (d, 1 H, J = 1.5 Hz), 6.22 (s, 1 H), 7.25 (d, 2 H, J = 8.2 Hz), 7.43 (m, 5 H), 7.51 (d, 2 H, J = 8.2 Hz). ¹³C NMR (125 MHz, CDCl₃): δ = 205.77, 198.32, 176.15, 142.00, 136.22, 132.21, 131.47, 129.55, 129.06, 128.83, 127.08, 124.99, 72.31, 46.41, 37.57, 30.19, 21.42. IR(neat): ν = 3536, 3052, 1688, 1594, 1182, 1082, 772, 732 cm^-1. EIMS: m/z (%) = 316(38) [M⁺ - 16], 193(55), 57(100). HRMS (EI): Calcd for C₂₁H₂₀O₃S: 352.1133. Found: 352.1102.

13

Typical Procedure: Preparation of (4 S )-4-[2-(2,4-Dimethylphenyl)-2-oxoethyl]-3-methylcyclopent-2-enone(14). To a solution of (50 mg, 0.14 mmol) in MeOH (20 mL) was added formic acid (60 µL, 1.56 mmol) and activated zinc dust (400 mg, 6.1 mmol) at -20 °C. The mixture was stirred for 10 min at that temperature and then filtered. The filtrate was evaporated in vacuo and the residue was shaken with a mixture of aq NaHCO₃ and EtOAc. The aq layer was extracted with EtOAc and the combined organic layers were dried (MgSO₄) and evaporated. The residue was purified by flash chromatography (hexane-EtOAc, 5:1) to give 14 (24 mg, 80%) as a colorless solid; mp 74-75 °C (hexane-EtOAc). The spectroscopic data of the product were identical with those of the racemic sample reported previously (ref. [7] ). The ee of the cyclopentenone was determined to be 98% (HPLC conditions: Daicel Chiralcel OD-H, 45 × 250 mm, λ = 254 nm, hexane-propan-2-ol, 9:1, t_major = 42.6 min, t_minor = 35.4 min). Compounds 10, 11 and 12 showed identical spectroscopic data with the corresponding racemic samples previously reported (ref. [7] ). Other new compounds gave satisfactory spectroscopic and analytical and/or high resolution mass data.