Base-Catalyzed Ethanolysis of α-Diethoxyphosphoryl-γ-lactones: A Facile Synthesis of Cyclopropanecarboxylates

Abstract

A range of alkyl- and alkenylcyclopropanecarboxylic acid ethyl esters has been stereoselectively prepared by treatment of substituted α-diethoxyphosphoryl-γ-lactones with sodium ethoxide in tetrahydrofuran.

Key words

Wittig-type cyclopropanation - γ-lactones - alkylation - cyclopropanecarboxylates - stereoselective synthesis

References

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7

General Procedure for the Preparation of α-Substituted and α,γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones 9a-d and 9e-g.
A solution of α-diethoxyphosphoryl-γ-lactone (5, 17.0 mmol) in THF (10 mL) was added dropwise under argon atmosphere at -78 °C to a stirred solution of LDA prepared from BuLi (10.6 mL, 17 mmol) and i-Pr₂NH (2.40 mL, 17 mmol) in THF (15 mL). When the addition was completed the reaction mixture was warmed to -5 °C and stirred for 0.5 h. After this time the mixture was cooled to -78 °C and allyl bromide (17 mmol) in THF (10 mL) was added. The stirring was continued for 1 h at this temperature and then the reaction mixture was warmed to r.t. and stirred for 20 h. The mixture was acidified to pH = 1 using 1 N HCl solution and THF was evaporated under reduced pressure. The residue was extracted with CHCl₃ (3 × 15 mL). Combined extracts were washed with H₂O (15 mL) and brine (15 mL), dried (MgSO₄) and evaporated. Crude products were distilled in vacuum (for 9a-c and 9e,f) or purified by column chromato-graphy (silica gel, eluent CHCl₃-acetone 5:1 for 9d and 9g).
Spectroscopic Data for 3-Benzyl-3-diethoxyphosphoryl-5-methyltetrahydrofuran-2-one (9f).
IR (film): 1764, 1256 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.22 (d, ³ J _HH = 6.2 Hz, 3 H, major), 1.25 (d, ³ J _HH = 5.5 Hz, 3 H, minor), 1.39 (td, ³ J _HH = 7.0 Hz, ⁴ J _PH = 0.6 Hz, 3 H, major + minor), 1.40 (td, ³ J _HH = 7.0 Hz, ⁴ J _PH = 0.5 Hz, 3 H, major + minor), 2.32 (dd, ³ J _PH = 13.7 Hz, ³ J _HH = 8.5 Hz, 1 H, major + minor), 2.40 (d, ³ J _HH = 8.5 Hz, 1 H, major + minor), 2.94 (dd, ² J _HH = 13.8 Hz, ³ J _PH = 9.7 Hz, 1 H, minor), 2.97 (dd, ² J _HH = 13.4 Hz, ³ J _PH = 9.2 Hz, 1 H, major), 3.29 (dq, ³ J _HH = 8.5 Hz, ³ J _HH = 6.2 Hz, 1 H, major + minor), 3.52 (dd, ² J _HH = 13.4 Hz, ³ J _PH = 6.0 Hz, 1 H, major), 3.60 (dd, ² J _HH = 13.4 Hz, ³ J _PH = 5.7 Hz, 1 H, minor), 4.20-4.36 (m, 4 H, major + minor), 7.16-7.30 (m, 5 H, major + minor). ¹³C NMR (62.9 MHz, CDCl₃): δ = 16.20 (2 d, ³ J _PC = 5.9 Hz), 21.12 (s), 35.46 (d, ² J _PC = 2.0 Hz), 38.20 (d, ² J _PC = 3.0 Hz), 51.30 (d, ¹ J _PC = 145.6 Hz), 63.02 (d, ² J _PC = 7.2 Hz), 63.50 (d, ² J _PC = 6.9 Hz), 74.36 (d, ³ J _PC = 8.3 Hz), 127.39 (s), 128.58 (s), 129.62 (s), 135.02 (d, ³ J _PC = 15.9 Hz), 174.77 (d, ² J _PC = 5.7 Hz). ³¹P NMR (101 MHz, CDCl₃): δ = 23.86 (minor), 24.14 (major). Anal. Calcd for C₁₆H₂₃O₅P: C, 58.89; H, 7.10. Found: C, 59.02; H, 7.05.

9

General Procedure for the Preparation of trans -3-Diethoxyphosphoryl-5,5-dimethyl-4-(2-methylprop-1-enyl)tetrahydrofuran-2-one (11b).
To a stirred solution of 2-methyl-1-propenylmagnesium bromide (2.04 mL, 20.15 mmol) in THF (5 mL) and catalytic amount of CuI (0.05 g, 0.26 mmol) a solution of lactone 10 (1.00 g, 4.03 mmol) in THF (5 mL) under argon atmosphere at -15 °C was added. The reaction mixture was and kept at this temperature for 72 h. Then the mixture was warmed to r.t., acidified to pH = 5 with sat. NH₄Cl solution and extracted with CH₂Cl₂ (4 × 10 mL). Combined extracts were dried (MgSO₄) and evaporated. Crude product was purified by column chromatography (silica gel, EtOAc-hexane 1:1 for 11a,b).
Spectroscopic Data.
IR (film): 1764, 1676, 1268 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.26 (s, 3 H), 1.31 (t, ³ J _HH = 7.0 Hz, 3 H), 1.37 (t, ³ J _HH = 7.1 Hz, 3 H), 1.47 (s, 3 H), 1.76 (d, ⁴ J _HH = 1.1 Hz, 3 H), 1.79 (d, ⁴ J _HH = 1.0 Hz, 3 H), 3.00 (dd, ² J _PH = 23.2 Hz, ³ J _HH = 11.8 Hz, 1 H), 3.64 (ddd, ³ J _PH = 16.1 Hz, ³ J _HH = 11.8 Hz, ³ J _HH = 10.1 Hz, 1 H), 4.13 (dq, ³ J _PH = 7.1 Hz, ³ J _HH = 7.1 Hz, 1 H), 4.27 (dq, ³ J _PH = 7.1 Hz, ³J_HH = 7.1 Hz, 1 H), 4.28 (dq, ³ J _PH = 7.1 Hz, ³ J _HH = 7.1 Hz, 1 H), 5.03 (ddd, ³ J _HH = 10.1 Hz, ⁴ J _HH = 1.1 Hz, ⁴ J _HH = 1.0 Hz, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.88 (d, ³ J _PC = 6.5 Hz), 16.02 (d, ³ J _PC = 6.2 Hz), 17.94 (s), 22.45 (s), 25.64 (s), 26.70 (s), 45.11 (d, ¹ J _PC = 151.3 Hz), 46.52 (d, ² J _PC = 2.1 Hz), 61.93 (d, ² J _PC = 6.7 Hz), 63.05 (d, ² J _PC = 6.3 Hz), 86.18 (d, ³ J _PC = 14.2 Hz), 119.81 (s), 136.90 (s), 170.00 (s). ³¹P NMR (101 MHz, CDCl₃): δ = 21.01. Anal. Calcd for C₁₄H₂₅O₅P: C, 55.25; H, 8.28. Found: C, 55.12; H, 8.20.

10

General Procedure for the Preparation of Ethyl Cyclopropanecarboxylates 12-23.
To a suspension of NaH (0.14 g, 6.0 mmol) and α-diethoxy-phosphoryl-γ-lactone 5b, 9a-g or 11a,b (6.0 mmol) in THF (15 mL) was added dropwise under argon atmosphere at r.t. a solution of EtOH (0.40 mL, 6.6 mmol) in THF (5 mL). The reaction mixture was stirred for 0.5 h and then was heated at reflux for time given in Table [3] . After cooling to r.t. brine (5 mL) was added and THF was evaporated. The residue was extracted with CH₂Cl₂ (3 × 15 mL) and dried (Na₂SO₄). After evaporation the crude products were purified by column chromatography (silica gel, eluent CHCl₃-hexane 80:20 for 9a-c and 50:50 for 22, 23 and CHCl₃-acetone 90:10 for 16, 17 and 21).
Spectroscopic Data for 1-Benzyl-2-methylcyclopropane-carboxylic Ethyl Ester (19).
IR (film): 1768 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 0.55 (dd, ³ J _HH = 6.5 Hz, ³ J _HH = 4.0 Hz, 1 H), 1.11 (t, ³ J _HH = 7.0 Hz, 3 H), 1.20 (d, ³ J _HH = 6.2 Hz, 3 H), 1.51-1.60 (m, 2 H), 2.78 (d, ² J _HH = 15.8 Hz, 1 H), 3.21 (d, ² J _HH = 15.8 Hz, 1 H), 4.03 (q, ³ J _HH = 7.0 Hz, 1 H), 4.03 (q, ³ J _HH = 7.0 Hz, 1 H), 7.16-7.27 (m, 5 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 14.02 (s), 14.03 (s), 21.76 (s), 22.24 (s), 27.69 (s), 33.26 (s), 60.37 (s), 125.68 (s), 128.00 (s), 128.39 (s), 140.60 (s), 175.25 (s). Anal. Calcd for C₁₄H₁₈O₂: C, 77.03; H, 8.31. Found: C, 76.89; H, 8.28.