Stereoselective α-Tertiary Alkylation of N-(Arylacetyl)oxazolidinones

Abstract

A method has been developed for the α-tertiary alkylation of zirconium enolates of N-(arylacetyl)oxazolidinones. This reaction directly installs an all-carbon quaternary center vicinal to a benzylic tertiary carbon in a highly diastereoselective manner.

Key words

alkylation - zirconium enolates - chiral auxiliary - oxazolidinones - quaternary carbon - asymmetric synthesis

• References and Notes


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• 8 4-Benzyl-3-(3,3-dimethyl-2-phenylbutanoyl)-5,5-dimethyl-1,3-oxazolidin-2-one; Typical Procedure An oven-dried 4 mL vial, equipped with a magnetic stirrer bar, was charged with oxazolidinone 1 (129 mg, 0.4 mmol) and ZrCl₄ (98 mg, 1.05 equiv) in a nitrogen-filled glovebox. CHCl₃ (1.0 mL) was added, and the mixture was stirred at rt for 10 min. Et₃N (0.17 mL, 3.0 equiv) was then added and stirring was continued at rt for 45 min. t-BuBr (67 μL, 1.5 equiv) and SnCl₄ (50 μL, 1.1 equiv) were added sequentially, and the mixture was stirred for 4 h at rt. The vial was opened and 0.5 M aq HCl (2 mL) was added. The mixture was transferred to a separatory funnel by using CH₂Cl₂ (3 × 1 mL) and 0.5 M aq HCl (3 × 1 mL) to wash the vial. After the layers were separated, the aqueous layer was extracted with CH₂Cl₂ (3 × 5 mL). The combined organic layers were dried (Na₂SO₄), filtered, and concentrated in vacuo. The resulting crude product was purified by column chromatography (silica gel, 10% Et₂O–hexanes) to give a white solid; yield: 0.117 g (77%, dr 50:1); [α]_D ²⁵ 82.3 (c 1.00, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 7.41–7.36 (m, 2 H), 7.33–7.21 (m, 8 H), 5.03 (s, 1 H), 4.46 (dd, J = 9.7, 3.9 Hz, 1 H), 3.22 (dd, J = 14.3, 3.8 Hz, 1 H), 2.90 (dd, J = 14.4, 9.7 Hz, 1 H), 1.27 (s, 3 H), 1.01 (s, 3 H), 1.00 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 173.43, 152.32, 137.04, 135.70, 130.70, 129.04, 128.64, 127.72, 127.13, 126.72, 81.53, 63.91, 57.22, 35.51, 35.02, 28.02, 22.13. HRMS-ESI: m/z [M + Na]⁺ calcd for C₂₄H₂₉NNaO₃: 402.2045; found: 402.2052.