Catalytic Asymmetric α-Amination of α-Branched Ketones via Enol Catalysis

Abstract

We report a highly enantioselective α-amination of α-branched ketones catalyzed by a chiral phosphoric acid employing azodicarboxylates as reagents. The desired products were obtained in good to excellent yields and enantioselectivities.

Key words

asymmetric synthesis - Brønsted acid catalysis - electrophilic amination - α-branched ketones - enol catalysis - azodicarboxylates

• References and Notes

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• 14 Representative Procedure: To a solution of the catalyst (S)-4c (7.0 mg, 0.01 mmol, 5 mol%) and the ketone 1b (24.3 μL, 0.2 mmol) in MeCN (0.1 mL) azodicarboxylate 2a (74.6 mg, 96%, 0.24 mmol) was added and the resulting mixture was stirred at r.t. for 24 h. The crude reaction mixture was directly purified by silica gel column chromatography (CH₂Cl₂–MTBE = 0% to 5%) giving 3a (69.6 mg, 85%) as a colorless oil. ¹H NMR (500 MHz, CDCl₃): δ = 7.01–7.42 (m, 10 H), 6.44–6.82 (m, 1 H), 4.79–5.19 (m, 4 H), 1.08–2.74 (m, 11 H). ¹³C NMR (125 MHz, CDCl₃): δ = 209.1, 156.7, 155.8, 135.6, 135.5, 128.6, 128.5, 128.4, 128.3, 128.1, 70.7, 69.7, 68.6, 68.4, 68.0, 67.8, 39.6, 39.0, 38.3, 29.7, 29.2, 26.5, 21.8, 21.8, 21.0, 19.8. HRMS (ESI, +ve): m/z [M + Na] calcd for C₂₃H₂₆N₂NaO₅: 433.1734; found: 433.1732. HPLC (Chiralcel OJ-3R, MeCN–H₂O = 50:50, flow rate: 1.0 mL/min, λ = 220 nm): t _R(major) = 15.2 min, t _R(minor) = 12.2 min.