Intermolecular Cycloaddition of Ethyl Glyoxylate O-tert-Butyldimethyl­silyloxime with Alkenes

Abstract

Ethyl glyoxylate O-tert-butyldimethylsilyloxime, on treatment with various alkenes in the presence of BF₃·OEt₂, ­generated a C-ethoxycarbonyl N-boranonitrone intermediate, which underwent intermolecular cycloaddition to afford 3-(ethoxy­carbonyl)isoxazolidines in moderate to high yields.

cycloaddition - boron trifluoride - N-boranonitrone - ­alkenes - cycloadducts

References and Notes

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9

For completion of the cycloaddition, 2 equiv of BF₃·OEt₂ are essential. See ref. 6.

10

During study on the intramolecular cycloaddition of N-boranonitrone, we observed the tendency that electron-rich carbon atom in the olefin attacks the nitrone-carbon. For example, reaction of oxime 15a with BF₃·OEt₂ afforded cycloadduct 16 bearing a bicyclo[3.3.0] system, whereas a similar reaction of oxime 15b afforded cycloadduct 17 having a bicyclo[3.2.1] system (Scheme [7] ). See ref 6b.

Scheme 7

11 Adachi I, Yamamori T, and Hiramatsu Y. inventors; Jpn. Patent,  50939. 

12

Preparation of Ethyl 2-[ tert -Butyldimethylsilyl-oxyimino]acetate (12): The mixture of ethyl 2-hydroxy-iminoacetate (11;¹¹ 0.91 g, 7.8 mmol), tert-butylchloro-dimethylsilane (1.77 g, 11.8 mmol), and imidazole (1.60 g, 23.5 mmol) in DMF (12 mL) was stirred at r.t. for 46 h. The reaction mixture was poured into H₂O and extracted with Et₂O. The combined organic phases were washed with brine and dried with MgSO₄. The solvent was removed by rotary evaporation and the crude product was purified by column chromatography on silica gel with hexane-Et₂O (20:1) to afford 12 (1.77 g, 98%) as a colorless oil. IR: 2934, 1749, 1728 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.62 (s, 1 H), 4.30 (q, J = 7.1 Hz, 2 H), 1.33 (t, J = 7.1 Hz, 3 H), 0.95 (s, 9 H), 0.23 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 162.3, 146.1, 61.3, 25.7, 18.0, 14.0, -5.4. LRMS: m/z = 231.14. HRMS (EI): m/z calcd for C₁₀H₂₁NO₃Si: 231.1291; found: 231.1270.

13

Typical Procedure for the Cycloaddition: To a solution of 12 (300 mg, 1.3 mmol) in DCE (10 mL) were added 7e (1.1 mL, 13 mmol) and BF₃·OEt₂ (310 µL, 2.9 mmol) at r.t., and then the mixture was heated at 60 °C for 2 h. The reaction was monitored by TLC. After cooling, the reaction mixture was poured into sat. NaHCO₃ solution and was extracted with CHCl₃. The combined organic layers were washed with brine and dried with MgSO₄. The residue was concentrated under reduced pressure. The crude product was purified by chromatography on silica gel with hexane-EtOAc (3:2) to give two diastereomers, 14e (160 mg, 61%) and 14e′ (47 mg, 18%) as light brown oils. 14e: IR (neat): 1733 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 5.90 (br s, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 4.12 (d, J = 7.5 Hz, 1 H), 2.73 (dd, J = 7.0, 14.5 Hz, 1 H), 1.82-1.72 (m, 4 H), 1.59-1.45 (m, 2 H), 1.40 (s, 3 H), 1.29 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 164.4, 95.5, 66.0, 61.1, 55.7, 39.5, 28.2, 26.4, 24.8, 14.2. LRMS: m/z = 199. HRMS (EI): m/z calcd for C₁₀H₁₇NO₃: 199.1208; found: 199.1187. 14e′: ¹H NMR (300 MHz, CDCl₃): δ = 5.93 (br s, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 3.56 (d, J = 6.6 Hz, 1 H), 2.49 (br s, 1 H), 1.92-1.65 (m, 6 H), 1.45-1.32 (m, 3 H), 1.29 (t, J = 7.1 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.3, 96.1, 70.2, 61.4, 59.5, 38.5, 32.2, 24.4, 23.5, 14.1.

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