Direct Intramolecular Catalytic Enantioselective Alkylation of Oxazolidinone Bromoalkanoate Imides

Abstract

Bromoalkanoate imides undergo intramolecular alkylation to form cyclopentane carboximides using catalytic amounts of magnesium bromide in the presence of DBU. Addition of PyBox ligands affords alkylation products with moderate enantioselectivity.

Key words

alkylation - cyclization - imides - magnesium - catalysis

• References and Notes

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• 16 General Procedure: In a glove box, an oven-dried 15-mL pressure tube was charged with MgBr₂·OEt₂ (10.3 mg, 0.040 mmol, 10 mol%) and 4 mL of substrate 3a in a 0.1 M solution in CHCl₃ (116.9 mg, 0.40 mmol, 1 equiv). The tube was capped and the mixture was shaken by hand for 30 s. The ligand (400 μL, 0.040 mmol, 10 mol%) was then added via syringe from a 0.1 M stock solution in CHCl₃. The mixture was shaken by hand for another 30 s and DBU was then added from a 0.1 M solution in CHCl₃ (0.60 mmol, 6 mL, 1.5 equiv) to the tube. This mixture was shaken for 30 s and let stand 24 h without agitation at r.t. After this time, the reaction was quenched by addition of 10% CuSO₄ solution (ca. 25 mL) and shaken. The product was extracted with CH₂Cl₂ (4 × 20 mL), the combined extracts were dried over MgSO₄ and concentrated in vacuo. The residue was purified by chromatography on silica gel (hexanes–EtOAc, 1:0, 3:1) to yield 4a as a clear oil (83.5 mg, 98%). 3-(2,2-Dimethylcyclopentanecarbonyl)oxazolidin-2-one (4a): IR (KBr): 2957, 2918, 2366, 1775, 1691, 1382, 1192, 1021 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 4.36 (t, J = 7.6 Hz, 2 H), 3.94–4.08 (m, 3 H), 1.99–2.08 (m, 1 H), 1.85–1.96 (m, 1 H), 1.77–1.84 (m, 1 H), 1.65–1.72 (m, 1 H), 1.54–1.61 (m, 1 H), 1.41–1.49 (m, 1 H), 1.09 (s, 3 H), 0.93 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 176.2, 153.6, 61.6, 50.4, 44.5, 42.9, 41.3, 28.7, 28.4, 24.4, 22.8. HRMS (ESI): m/z [M + H⁺] calcd for C₁₁H₁₇NO₃: 212.1281; found: 212.1281. 3-(Cyclopentanecarbonyl)oxazolidinone (4b): IR (film): 2960, 2872, 1772, 1692, 1383, 1220, 1109, 1040 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 4.40 (t, J = 8.0 Hz, 2 H), 4.00 (t, J = 8.0 Hz, 2 H), 3.86 (q, J = 8.0 Hz, 1 H), 1.93–1.99 (m, 2 H), 1.60–1.83 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 176.8, 153.3, 61.8, 42.9, 42.7, 29.9, 29.7, 26.0. HRMS (ESI): m/z [M + Na⁺] calcd for C₉H₁₃NO₃: 206.0788; found: 206.0788. 3-(3,3-Dimethylcyclopentanecarbonyl)oxazolidin-2-one (4c): IR (film): 2959, 2872, 1771, 1690, 1478, 1381, 1361, 1251, 1195, 1102, 1042, 1016 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 4.39 (t, J = 7.8 Hz, 2 H), 3.96–4.07 (m, 3 H), 1.88–2.08 (m, 2 H), 1.43–1.82 (m, 4 H), 1.06 (br s, 3 H), 1.01 (br s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 176.8, 153.2, 61.8, 44.0, 42.9, 42.3, 40.6, 39.8, 29.0, 28.6, 28.4. HRMS (ESI): m/z [M + Na⁺] calcd for C₁₁H₁₇NO₃: 234.1101; found: 234.1100. 3-(3-Methylenecyclopentanecarbonyl)oxazolidin-2-one (4d): IR (neat): 1773, 1738, 1695 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 4.87 (m, 2 H), 4.41 (t, J = 8.2 Hz, 2 H), 3.93–4.04 (m, 3 H), 2.54–2.68 (m, 2 H), 2.43–2.51 (m, 1 H), 2.30–2.39 (m, 1 H), 2.04–2.12 (m, 1 H), 1.83–1.93 (m, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 175.5, 153.2, 150.3, 105.9, 61.9, 43.1, 42.8, 36.2, 32.2, 29.9. HRMS (ESI): m/z [M + H⁺] calcd for C₁₀H₁₄NO₃: 196.0968; found: 196.0970.
• 17 In addition, we examined the alkylation of a 4-(2-bromo-ethoxy)butanimide which would form a six-membered ring. No product formation was observed.