Synthesis of Sulfinimines by Direct Condensation of Sulfinamides with Aldehydes Using Cs₂CO₃ as an Activating and Dehydrating Reagent

Abstract

Chiral sulfinimines were prepared from chiral sulfinamides and aldehydes in CH₂Cl₂ in the presence of cesium carbonate as an amine-activating and dehydrating reagent.

Key words

sulfinimines - sulfinamides - cesium carbonate - dehydrations - amine activation

References

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8

At the reflux temperature of each solvent, considerable decomposition occurred (except CH₂Cl₂).

10

Representative Experimental Procedure (Table 3, Entry 1): To a solution of 1 [5] (80.0 mg, 0.515 mmol) in CH₂Cl₂ (2.6 mL) were added Cs₂CO₃ (168 mg, 0.515 mmol) and benzaldehyde (0.0523 mL, 0.515 mmol). The resulting suspension was vigorously stirred at 40-45 °C for 8 h. The reaction mixture was filtered with Celite and the filter cake was washed with CH₂Cl₂. The filtrates and washings were combined and concentrated. The residue was chromatographed on silica gel (flash) with hexane-EtOAc = 9:1 to afford sulfinimine 6 (119 mg) in 95% yield. The ee of 6 was 97% determined by chiral HPLC analysis (Daicel Chiralcel OD column, 4.6 × 250 mm, 99.5:0.5 hexane-IPA; 1 mL/min, 254 nm, t _R = 36.6 min; enantiomer of 6, t = 32.7 min), which was identical with that of 1 used (Daicel Chiralcel OD column, 4.6 × 250 mm, 90:10 hexane-IPA; 1 mL/min, 254 nm, t _R = 18.0 min; enantiomer of 1, t _R = 14.9 min). Compound 6: mp 78-79 °C (lit. [5a] [b] 77-78 °C, lit. [5c] 80-81 °C); [α]_D ²⁹ +114 (c 1.00, CHCl₃) {lit. [5a] [α]_D ²⁰ +117.3 (c 1.77, CHCl₃), lit. [5b] [α]_D ²⁰ +117.5 (c 1.6, CHCl₃), lit. [5c] [α]_D ²⁰ +122.8 (c 1.2, CHCl₃)}. ¹H NMR (300 MHz, CDCl₃, TMS = 0 ppm): δ = 2.40 (3 H, s), 7.32 (2 H, d, J = 8.0 Hz), 7.41-7.52 (3 H, m), 7.64 (2 H, d, J = 8.0 Hz), 7.82-7.87 (2 H, m), 8.75 (1 H, s). Sulfinimine 8 (Table [5] , entry 1) was obtained after silica-gel(flash) column chromatography (CH₂Cl₂) in 80% isolated yield by the same procedure as described above. The ee of 8 was 99% determined by chiral HPLC analysis (Daicel Chiralcel OD column, 4.6 × 250 mm, 95:5 hexane-IPA; 1 mL/min, 254 nm, t _R = 5.51 min; enantiomer of 6, t _R = 6.96 min), which was identical with that of 7 used (Daicel Chiralcel OD column, 4.6 × 250 mm, 96:4 hexane-IPA; 1 mL/min, 222 nm, t _R = 41.6 min; enantiomer of 7, t _R = 35.5 min). Compound 8: [α]_D ²⁸ +103 (c 1.00, CHCl₃) {lit. [3] [α]_D ²⁰ +104 (c 1.00, CHCl₃); enantiomer of 8, lit. [4c] [α]_D ²³ -122 (c 1.00, CHCl₃)}. ¹H NMR (300 MHz, CDCl₃, TMS = 0 ppm): δ = 1.28 (9 H, s), 7.44-7.55 (3 H, m), 7.83-7.89 (2 H, m), 8.59 (1 H, s).