Ligand-Controlled Intramolecular Carbonylative Cyclization of 1,1-Diethynyl Acetates: New Entry to the Functionalized 4-Cyclopentene-1,3-diones

Keisuke Kato; Ryuhei Teraguchi; Shigeo Yamamura; Tomoyuki Mochida; Hiroyuki Akita; Tat’yana A. Peganova; Nikolai V. Vologdin; Oleg V. Gusev

doi:10.1055/s-2007-967944

LETTER

Ligand-Controlled Intramolecular Carbonylative Cyclization of 1,1-Diethynyl Acetates: New Entry to the Functionalized 4-Cyclopentene-1,3-diones

Keisuke Kato*^a, Ryuhei Teraguchi^a, Shigeo Yamamura^a, Tomoyuki Mochida^b, Hiroyuki Akita*^a, Tat’yana A. Peganova^c, Nikolai V. Vologdin^c, Oleg V. Gusev^c
^a Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
Fax: +81(474)721825; e-Mail: kkk@phar.toho-u.ac.jp;
^b Department of Chemistry, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
^c A. N. Nesmeyanov Institute of Organoelement Compounds of the , Russian Academy of Sciences, Vavilov St.28, 119991 Moscow, Russian Federation

Abstract

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Abstract

The carbonylative cyclization of 1,1-diethynyl acetates mediated by Phbox/Pd(TFA)₂ afforded a functionalized 4-cyclopentene-1,3-dione as a major product. In the absence of box ligand, a methoxycarbonylated orthoester was obtained predominantly.

Key words

palladium - bisoxazoline - carbonylative cyclization - 1,1-diethynyl acetate - carbonylation

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References

References and Notes

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General Procedure for the Reaction of 1.
A 30 mL two-necked round-bottomed flask, containing a magnetic stirring bar, Pd(TFA)₂ (0.015 mmol), ligand (0.0225 mmol), p-benzoquinone (0.6 mmol) and MeOH (5 mL) was fitted with a rubber septum and a three-way stopcock connected to a balloon filled with CO. The apparatus was purged with CO by pumping-filling via the three-way stopcock. To the stirred solution the substrate 1 (0.3 mmol) was added dropwise (3 × 1 mL) via a syringe at 0 °C. After being stirred for a certain period at the appropriate temperature, the mixture was diluted with CH₂Cl₂ (30 mL), and washed with 2% Na₂SO₃ aq (30 mL). The organic layers were separated, the aqueous layer was extracted with CH₂Cl₂ (30 mL), and the combined organic layers were dried with MgSO₄ and concentrated in vacuo. The crude product was purified by column chromatography on silica gel. The fraction eluted with hexane-EtOAc (100:1 to 50:1) afforded 2 and 3 (10:1). The products 2 were separated to give each diastereomer by preparative TLC. The ee of each diastereomer was determined by HPLC using Chiralcel OD column (hexane-EtOH = 150:1, FL = 1.0, for 3a-2) and Chiralcel OF column (hexane-EtOH = 150:1, FL = 0.5, for 3a-1). The relative stereochemistry of 3 was estimated as shown in Figure [2] , based on NOE experiments.
Compound 2a: slightly yellow needles; mp 56 °C. ¹H NMR (CDCl₃): δ = 2.80-2.84 (2 H, m), 2.89 (2 H, s), 2.95-2.99 (2 H, m), 3.44 (6 H, s), 5.35 (1 H, s), 7.18-7.31 (5 H, m). ¹³C NMR (CDCl₃): δ = 26.5, 34.4, 41.1, 55.5, 98.7, 126.3, 128.4, 128.5, 141.0, 152.3, 161.4, 198.8, 200.3. MS-FAB: m/z = 275 [M⁺ + H]. IR (KBr): 2933, 1742, 1706 cm^-1. Anal. Calcd (%) for C₁₆H₁₈O₄: C, 70.06; H, 6.61. Found: C, 69.86; H, 6.57.
Compound 3a-1 (more polar diastereomer): colorless needles; mp 44 °C. ¹H NMR (CDCl₃): δ = 1.71 (3 H, s), 2.24-2.30 (1 H, m), 2.72 (1 H, s), 2.77-2.90 (2 H, m), 2.95-3.04 (1 H, m), 3.39 (3 H, s), 3.70 (3 H, s), 5.50 (1 H, s), 7.16-7.30 (5 H, m). ¹³C NMR (CDCl₃): δ = 24.1, 30.2, 40.2, 50.3, 51.2, 74.5, 79.5, 81.5, 91.0, 124.2, 126.1, 128.5, 128.5, 141.0, 165.9, 168.0. HRMS (EI): m/z [M⁺] calcd for C₁₈H₂₀O₅: 316.1311; found: 316.1304. IR (KBr): 3269, 2950, 2121, 1720, 1666 cm^-1.
Compound 3a-2 (less polar diastereomer): colorless needles; mp 35 °C. ¹H NMR (CDCl₃): δ = 1.76 (3 H, s), 2.18-2.27 (1 H, m), 2.71 (1 H, s), 2.84-2.92 (1 H, m), 3.03-3.12 (2 H, m), 3.45 (3 H, s), 3.69 (3 H, s), 5.47 (1 H, s), 7.21-7.28 (5 H, m). ¹³C NMR (CDCl₃): δ = 24.0, 30.5, 39.3, 49.6, 51.2, 74.6, 80.0, 80.3, 91.1, 124.5, 126.1, 128.5, 128.5, 141.2, 166.0, 167.4. HRMS (EI): m/z [M⁺] calcd for C₁₈H₂₀O₅: 316.1311; found 316.1318. IR (KBr): 3246, 2949, 2113, 1708, 1658 cm^-1.
Compound 2b: slightly yellow oil. ¹H NMR (CDCl₃): δ = 0.88 (3 H, t, J = 6.8 Hz), 1.22-1.56 (12 H, m), 2.65 (2 H, t, J = 7.8 Hz), 2.89 (2 H, s), 3.45 (6 H, s), 5.36 (1 H, s). ¹³C NMR (CDCl₃): δ = 14.1, 22.7, 24.4, 28.4, 29.1, 29.2, 30.0, 31.8, 41.2, 55.5, 98.8, 151.7, 162.8, 198.9, 200.7. HRMS (EI): m/z [M⁺] calcd for C₁₆H₂₆O₄: 282.1831; found: 282.1829. IR (neat): 2927, 1745, 1706 cm^-1.
Compound 3b-1 (more polar diastereomer): colorless oil. ¹H NMR (CDCl₃): δ = 0.88 (3 H, t, J = 8.0 Hz), 1.22-1.35 (10 H, m), 1.39-1.52 (1 H, m), 1.57-1.71 (1 H, m), 1.68 (3 H, s), 1.99-2.06 (1 H, m), 2.41-2.49 (1 H, m), 2.66 (1 H, s), 3.36 (3 H, s), 3.70 (3 H, s), 5.47 (1 H, s). ¹³C NMR (CDCl₃): δ = 14.1, 22.7, 23.8, 24.1, 29.2, 29.3, 29.4, 31.9, 38.4, 50.3, 51.1, 74.1, 79.9, 82.1, 90.6, 124.0, 165.9, 168.4. HRMS (EI): m/z [M⁺] calcd for C₁₈H₂₈O₅: 324.1937; found: 324.1924. IR (KBr): 3281, 2927, 2120, 1723, 1657 cm^-1.
Compound 3b-2 (less polar diastereomer): colorless oil. ¹H NMR (CDCl₃): δ = 0.88 (3 H, t, J = 7.0 Hz), 1.22-1.40 (10 H, m), 1.49-1.62 (1 H, m), 1.68-1.78 (1 H, m), 1.72 (3 H, s), 1.93-2.00 (1 H, m), 2.64-2.72 (1 H, m), 2.65 (1 H, s), 3.31 (3 H, s), 3.70 (3 H, s), 5.45 (1 H, s). ¹³C NMR (CDCl₃): δ = 14.1, 22.7, 24.1, 24.1, 29.2, 29.4, 29.5, 31.9, 37.4, 49.5, 51.1, 74.2, 80.4, 80.8, 90.8, 124.3, 166.0, 167.9. HRMS (EI): m/z [M⁺] calcd for C₁₈H₂₈O₅: 324.1937; found: 324.1965. IR (KBr): 3296, 2931, 2119, 1725, 1657 cm^-1.
Compound 2c: colorless oil. ¹H NMR (CDCl₃): δ = 0.90 (3 H, t, J = 7.2 Hz), 1.31-1.37 (4 H, m), 1.47-1.54 (2 H, m), 2.65 (2 H, t, J = 7.8 Hz), 2.89 (2 H, s), 3.45 (6 H, s), 5.37 (1 H, s). ¹³C NMR (CDCl₃): δ = 13.9, 22.3, 24.3, 28.1, 32.1, 41.2, 55.5, 98.7, 151.7, 162.8, 199.0, 200.7. HRMS (EI): m/z [M⁺] calcd for C₁₃H₂₀O₄: 240.1362; found: 240.1352. IR (neat): 2932, 1745, 1706 cm^-1.
Compound 3c-1 (more polar diastereomer): colorless oil. ¹H NMR (CDCl₃): δ = 0.89 (3 H, t, J = 7.2 Hz), 1.29-1.37 (4 H, m), 1.44-1.52 (1 H, m), 1.58-1.66 (1 H, m), 1.69 (3 H, s), 1.98-2.06 (1 H, m), 2.40-2.49 (1 H, m), 2.67 (1 H, s), 3.36 (3 H, s), 3.70 (3 H, s), 5.47 (1 H, s). ¹³C NMR (CDCl₃): δ = 13.9, 22.4, 23.4, 24.0, 31.4, 38.3, 50.2, 51.1, 74.1, 79.8, 82.0, 90.6, 124.0, 165.9, 168.4. HRMS (EI): m/z [M⁺] calcd for C₁₅H₂₂O₅: 282.1467; found: 282.1419. IR (KBr): 3248, 2952, 2122, 1710, 1656 cm^-1. Anal. Calcd for C₁₅H₂₂O₅: C, 63.83; H, 7.85. Found: C, 63.71; H, 7.89.
Compound 3c-2 (less polar diastereomer): colorless oil. ¹H NMR (CDCl₃): δ = 0.90 (3 H, t, J = 6.8 Hz), 1.31-1.37 (4 H, m), 1.51-1.61 (1 H, m), 1.68-1.79 (1 H, m), 1.73 (3 H, s), 1.92-2.00 (1 H, m), 2.65-2.72 (1 H, m), 2.65 (1 H, s), 3.31 (3 H, s), 3.70 (3 H, s), 5.45 (1 H, s). ¹³C NMR (CDCl₃): δ = 13.9, 22.5, 23.7, 24.0, 31.5, 37.3, 49.5, 51.1, 74.2, 80.4, 80.8, 90.8, 124.3, 166.0, 167.9. HRMS (EI): m/z [M⁺] calcd for C₁₅H₂₂O₅: 282.1467; found: 282.1466. IR (KBr): 3298, 2952, 2120, 1723, 1658 cm^-1.
Compound 2d: colorless oil. ¹H NMR (CDCl₃): δ = 1.41 (3 H, s), 2.93 (2 H, s), 3.09 (2 H, s), 3.49 (6 H, s), 3.91-3.99 (4 H, m), 5.39 (1 H, s). ¹³C NMR (CDCl₃): δ = 25.2, 32.7, 41.6, 56.1, 64.8, 100.1, 109.3, 153.1, 156.5, 198.5, 199.9. HRMS (EI): m/z [M⁺] calcd for C₁₃H₁₈O₆: 270.1103; found: 270.1109. IR (neat): 3438, 2937, 1750, 1708 cm^-1.
Compound 3d: inseparable mixture of diastereomers (ratio = 2.4:1); colorless oil. ¹H NMR (CDCl₃): δ (major diastereomer) = 1.56 (3 H, s), 1.73 (3 H, s), 2.44 (1 H, d, J = 15.2 Hz), 2.71 (1 H, s), 2.96 (1 H, d, J = 15.2 Hz), 3.38 (3 H, s), 3.70 (3 H, s), 3.87-4.08 (4 H, m), 5.46 (1 H, s). ¹H NMR (CDCl₃): δ = (minor diastereomer) = 1.61 (3 H, s), 1.76 (3 H, s), 2.18 (1 H, d, J = 14.8 Hz), 2.72 (1 H, s), 3.32 (1 H, d, J = 14.8 Hz), 3.35 (3 H, s), 3.70 (3 H, s), 3.87-4.08 (4 H, m), 5.43 (1 H, s). ¹³C NMR (CDCl₃): δ (major diastereomer) = 23.7, 25.9, 44.9, 50.4, 51.1, 64.3, 64.5, 74.2, 79.1, 79.9, 90.1, 108.2, 124.5, 165.9, 168.8. ¹³C NMR (CDCl₃): δ (minor diastereomer) = 24.1, 25.5, 43.9, 49.6, 51.1, 64.4, 64.5, 74.7, 77.9, 80.1, 90.3, 108.5, 125.2, 165.9, 168.5. HRMS (EI): m/z [M⁺] calcd for C₁₅H₂₀O₇: 312.1209; found: 312.1191. IR (KBr): 3248, 2907, 2117, 1707, 1650 cm^-1.Compound 2e: colorless oil. ¹H NMR (CDCl₃): δ = 2.88 (2 H, s), 3.45 (6 H, s), 4.04 (2 H, s), 5.43 (1 H, s), 7.17-7.35 (5 H, m). ¹³C NMR (CDCl₃): δ = 30.0, 41.3, 55.6, 98.7, 126.7, 128.5, 129.6, 136.6, 151.8, 159.6, 198.8, 200.3. HRMS (EI): m/z [M⁺] calcd for C₁₆H₁₆O₄: 260.1049; found: 260.1054. IR (KBr): 2935, 1747, 1706 cm^-1.Compound 3e-1 (more polar diastereomer): colorless needles; mp 64 °C. ¹H NMR (CDCl₃): δ = 1.23 (3 H, s), 2.70 (1 H, s), 3.33 (3 H, s), 3.54 (1 H, d, J = 14.0 Hz), 3.78 (3 H, s), 3.81 (1 H, d, J = 14.0 Hz), 5.54 (1 H, s), 7.23-7.30 (5 H, m). ¹³C NMR (CDCl₃): δ = 23.3, 43.9, 50.4, 51.3, 74.7, 80.2, 82.1, 91.3, 124.4, 127.4, 128.0, 131.3, 134.6, 166.1, 167.6 MS (EI): m/z = 302 [M⁺]. IR (KBr): 3262, 2115, 1716, 1657 cm^-1. Anal. Calcd for C₁₇H₁₈O₅: C, 67.54; H, 6.00. Found: C, 67.63; H, 6.05.
Compound 3e-2 (less polar diastereomer): colorless needles; mp 67 °C. ¹H NMR (CDCl₃): δ = 1.70 (3 H, s), 2.65 (1 H, s), 3.05 (3 H, s), 3.61 (1 H, d, J = 14.0 Hz), 3.77 (3 H, s), 3.87 (1 H, d, J = 14.0 Hz), 5.55 (1 H, s), 7.25-7.38 (5 H, m). ¹³C NMR (CDCl₃): δ = 24.1, 42.7, 49.5, 51.3, 75.2, 80.3, 80.4, 91.5, 124.5, 127.2, 128.0, 131.2, 135.0, 166.2, 167.2. MS (EI): m/z = 302 [M⁺]. IR (KBr): 3262, 2117, 1716, 1651 cm^-1. Anal. Calcd for C₁₇H₁₈O₅: C, 67.54; H, 6.00. Found: C, 67.19; H, 6.02.

Figure 2