Catalytic Asymmetric Electrophilic α-Amination of α-Cyanoketones in the Presence of Chiral Palladium Complexes

Abstract

The catalytic enantioselective electrophilic α-amination promoted by chiral palladium complexes is described. Treatment of α-cyanoketones with azodicarboxylates as electrophilic amination reagents under mild reaction conditions afforded the corresponding α-amino α-cyanoketones with excellent enantiomeric excesses (81-95% ee).

electrophilic amination - asymmetric catalysis - chiral palladium catalysts - α-cyanoketones

References and Notes

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13

General Procedure for the Amination of α-Cyanoketone
To a stirred solution of α-cyanoketone 3 (0.2 mmol) and catalyst 1a (BF₄) (9.6 mg, 0.01 mmol) in acetone (2 mL) was added tert-butyl azodicarboxylate (4d, 46 mg, 0.2 mmol) at r.t. The reaction mixture was stirred for 10 min to 20 h at r.t. The mixture was diluted with sat. NH₄Cl solution (10 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers were dried over MgSO₄, filtered, concentrated, and purified by flash chromatography (EtOAc-hexane, 1:3) to afford the α-aminated α-cyano-ketone 5. 2-Aminated 2-Cyano-1-indanone 5a
[α]_D ^²² -21.5 (c 1.45, CHCl₃, 92% ee). ^¹H NMR (200 MHz, CDCl₃): δ = 7.90-7.82 (m, 1 H), 7.74-7.66 (m, 1 H), 7.56-7.43 (m, 2 H), 7.01 (br s, 1 H), 4.07-3.83 (m, 2 H), 1.62-1.22 (m, 18 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 190.1, 155.5, 149.3, 136.9, 136.6, 132.2, 128.6, 126.5, 125.9, 115.6, 84.3, 82.2, 68.4, 40.9, 28.2, 27.8. MS (MSI): m/z
(%) = 387 [M⁺], 356 (10), 332 (70), 275 (32), 232 (8), 213 (12), 188 (7.5), 158 (8). ESI-HRMS: m/z calcd for C₂₀H₂₅N₃O₅ [M]⁺: 387.1794; found: 387.1802. HPLC (hexane-i-PrOH, 8:2, 254 nm, 1.0 mL/min, Chiralpak AD column): t _R = 5.8 min (minor), t _R = 7.7 min (major).