Convenient Access to Cycloalk-2-enone-Derived N-Sulfonyl Imines

Abstract

The first synthesis of N-tosyl imines from various cyclopent-2-enones and cyclohex-2-enones was achieved by direct condensation with tosyl amide in the presence of TiCl(OEt)₃ and Et₃N. In addition, N-tert-butylsulfonyl imines from five- to seven-membered cycloalk-2-enones were obtained through formation of the ­respective oximes and subsequent Hudson reaction. These compounds are easy to handle solids and they are interesting starting materials for a variety of transformations.

Key words

condensation - enones - imines - titanium - sulfonamides

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• 20 N-(Cyclohex-2-en-1-ylidene)-4-methylbenzene-sulfonamide (2a); Typical Procedure: To a solution of TiCl(OEt)₃ (4.37 g, 20.0 mmol) in toluene (10 mL) was added Et₃N (2.79 mL, 20.0 mmol). The resulting mixture was stirred for 5 min at r.t. before TsNH₂ (3.42 g, 20.0 mmol) was added, and the reaction mixture was heated to reflux for 15 min. A solution of 1a (961 mg, 10.0 mmol) in toluene (20 mL) was added dropwise over 15 min to the refluxing solution, and stirring was continued for 1 h. The reaction mixture was poured into a stirred and precooled (0 °C) suspension of NaHCO₃ (5.0 g) in acetone–H₂O (200 mL, 100:1), diluted with pentane (100 mL), dried over MgSO₄, and filtered. The filtrate was concentrated under reduced pressure, and the crude product was purified by flash chromatography (CH₂Cl₂; R _f = 0.26) on silica gel to furnish ketimine 2a (1.65 g, 66%) as a pale-yellow oil that crystallized in the freezer. ¹H NMR (300 MHz, CDCl₃): δ (62:38 E/Z-ratio, asterisk denotes minor isomer peaks) = 7.86 (m_c, 2 H), 7.32 (m_c, 2 H), 7.32* (m_c, 1 H), 6.94 (m_c, 1 H), 6.14 (dt, J = 10.0, 1.9 Hz, 1 H), 3.18 (m_c, 2 H), 2.54* (m_c, 2 H), 2.43 (s, 3 H), 2.40–2.30 (m, 2 H), 2.01–1.90 (m, 2 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 180.1, 178.0*, 151.6*, 150.6, 143.4, 138.6, 130.1, 129.4, 127.1*, 127.0, 124.1*, 35.5*, 31.4, 26.0*, 25.2, 22.1*, 21.53, 21.49. HRMS (ESI+): m/z [M + Na]⁺ calcd. for C₁₃H₁₅NO₂SNa: 272.0716; found: 272.0711. N-(Cyclohex-2-en-1-ylidene)-tert-butanesulfonamide (3a); Typical Procedure: To a solution of 1a (500 mg, 5.20 mmol) in MeOH–H₂O (9:1, 5.0 mL) in a 10 mL microwave reaction vessel were added hydroxylamine hydrochloride (398 mg, 5.72 mmol) and sodium acetate (512 mg, 6.24 mmol). The vessel was sealed, and the mixture was heated in a microwave reactor at 135 °C for 5 min and then cooled to r.t. The reaction mixtures of three such batches were combined, poured into H₂O (30 mL) and extracted with CHCl₃ (3 × 30 mL). The combined organic phases were washed with sat. NaHCO₃ (3 × 30 mL), dried over MgSO₄, and concentrated under reduced pressure to give the crude oxime (1.70 g). The crude oxime was dissolved in Et₂O (30 mL), Et₃N (3.18 mL, 23.0 mmol) was added, and the solution was cooled to –35 °C. Then, tert-butylsulfinyl chloride (4.28 g, 30.6 mmol) was added dropwise, and the resulting suspension was stirred at –35 °C for 1.5 h before the cooling bath was removed. Stirring was continued for 16 h, and the reaction mixture was then filtered over Celite and concentrated under vacuum. Purification by flash chromatography (pentane–EtOAc, 5:1; R _f = 0.38) on silica gel furnished ketimine 3a (1.62 g, 48%) as a pale-yellow oil that crystallized in the freezer. ¹H NMR (300 MHz, CDCl₃): δ (62:38 E/Z-ratio, asterisk denotes minor isomer peaks) = 7.12* (dt, J = 10.2, 2.0 Hz, 1 H), 6.90–6.80 (m, 1 H), 6.12 (dt, J = 10.0, 2.0 Hz, 1 H), 3.04 (t, J = 6.7 Hz, 2 H), 2.51* (t, J = 6.7 Hz, 2 H), 2.35–2.25 (m, 2 H), 1.97–1.83 (m, 2 H), 1.42 (s, 9 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 180.7, 178.7*, 150.4*, 149.8, 130.2, 124.5*, 58.7, 35.5*, 31.5, 26.0*, 25.2, 23.9, 22.2*, 21.5. HRMS (ESI+): m/z [M + H]⁺ calcd. for C₁₀H₁₈NO₂S: 216.1053; found: 216.1054.