New Aziridine Sulfide Ligands for Palladium-Catalyzed Asymmetric Allylic Alkylation

Abstract

Aziridine sulfides, a new type of chiral S,N-ligand, have been easily synthesized in a straightforward synthetic route, from an inexpensive and easily available chiral pool. They were used in the Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethymalonate anion, furnishing the alkylated product in excellent yields and stereoselectivity up to 99%.

asymmetric allylic alkylation - asymmetric catalyst - palladium - chiral pool - aziridine - S,N-ligands

References

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General Procedure for the Synthesis of Compound 6a. To a suspension of PPh₃ (1.048 g, 4 mmol) in THF (10 mL), DEAD (0.696 g, 4 mmol) was added at -78 °C under argon atmosphere. After 2 h, sulfide aminoalcohol 4a (1.148 g, 4 mmol) was added and the mixture was stirred for 12 h at r.t. Then, the solvent was evaporated and the residue was partitioned between H₂O and CH₂Cl₂. The organic layer was separated and the aqueous phase was extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were dried over MgSO₄ and the solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography (hexane-EtOAc 8:2). Analytical data for 6a: Yield: 61%; [α]_D ²⁰ -42 (c 0.56, CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃): δ = 7.33-7.18 (m, 10 H), 3.67 (d, 1 H, J = 13.2 Hz), 3.63 (d, 1 H, J = 13.2 Hz), 3.41 (d, 1 H, J = 13.2 Hz), 3.35 (d, 1 H, J = 13.2 Hz), 2.51 (dd, 1 H, J = 13.8 Hz, J = 5.8 Hz), 2.39 (dd, 1 H, J = 13.8 Hz, J = 5.8 Hz), 1.68-1.63 (m, 2 H), 1.39 (d, 1 H, J = 6.4 Hz). ¹³C NMR (100 MHz, CDCl₃): δ = 138.79, 138.33, 128.75, 128.26, 128.22, 128.07, 126.98, 126.74, 64.44, 39.24, 36.03, 34.14, 33.73. HRMS-ESI: m/z calcd for C₁₇H₁₉NS + H⁺: 270.1309; found: C₁₇H₁₉NS + H⁺: 270.1310.

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General Procedure for the Allylic Alkylation of 1,3-Diphenyl-2-propenyl Acetate with Sodium Dimethyl Malonate: A toluene (1 mL) solution of [Pd(η³-C₃H₅)Cl]₂ (9.1 mg, 25 µmol, 2.5 mol%) and the ligand (2.5 mol%) was stirred for 30 min under an argon atmosphere and then racemic 1,3-diphenyl-2-propenyl acetate (252 mg, 1.0 mmol) was added. The mixture was stirred for 10 min and a solution of sodium dimethyl malonate, prepared from dimethyl malonate (264 mg, 2.0 mmol) and NaH (48 mg, 2.0 mmol) in toluene (5 mL) was added at 0 °C. The mixture was stirred at 0 °C for the time given in Table [1] . The reaction was quenched with sat. NH₄Cl (aq) and extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were dried over MgSO₄. The solvent was evaporated and the crude product was purified by flash chromatography on silica gel (230-400 mesh) eluting with hexane-EtOAc (98:2). The ee was determined by HPLC (Chiralcel OD, 2-propanol/hexane = 1:99 flow rate 0.5 mL/min, λ = 254 nm).

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