Aza-Mannich Condensation of Sulfinimine Promoted by Tetrabutyl­ammonium Fluoride: Synthesis of α,β-Unsaturated Sulfinimine

Abstract

Self-condensation of tert-butanesulfinimine 5 was realized in the presence of tetrabutylammonium fluoride to afford α,β-unsaturated sulfinimine 8 in moderate to high yields with high geometric selectivities. The synthesized α,β-unsaturated sulfinimine 8 was demonstrated to be a versatile intermediate for the syntheses of enal 4 and chiral allyl amine 11.

tert-butanesulfinimine - self-condensation - tetrabutyl­ammonium fluoride - enal - chiral allyl amine

References and Notes

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7 The α,β-unsaturated sulfinimine 8 was also prepared by Ti(Oi-Pr)₄-catalyzed condensation of enal with tert-butanesulfinamide 9. See: McMahon JP. Ellman JA. Org. Lett.  2005,  7:  5393 

As a class of important plant and insect metabolites with antimicrobial properties, there are several examples describing preparation of enals. See:

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9

Representative Procedure of Self-Condensation: To a solution of 5 (1 mmol) in anhyd Et₂O (10 mL) was added anhyd TBAF (1.2 mmol, dried by P₂O₅ in vacuum condition). The biphasic mixture was stirred at r.t. for 30 min and then diluted with Et₂O (30 mL). After washing of the mixture with sat. NaCl solution, the solvent was evaporated to give a residue. The residue was either subjected to chromatography to give α,β-unsaturated sulfinimine 8 and tert-butanesulfinamide 9, or was subjected to hydrolysis to give enal 4.
Data for 8a (major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 0.85-0.91 (m, 6 H), 1.21 (s, 9 H), 1.23-1.50 (m, 18 H), 2.28 (q, J = 6.4 Hz, 2 H), 2.31-2.46 (m, 2 H), 6.20 (t, J = 7.6 Hz, 1 H), 8.05 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 22.4, 22.5, 22.6, 25.8, 28.7, 28.8, 28.9, 29.0, 29.3, 29.4, 29.7, 31.6, 31.7, 57.1, 139.5, 148.8, 166.3. HRMS: m/z [M + H⁺] calcd for C₂₀H₄₀NOS: 342.2825; found: 342.2813.
Data for 8b (major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 0.95 (t, J = 7.2 Hz, 3 H), 1.01 (t, J = 7.6 Hz, 3 H), 1.20 (s, 9 H), 1.47 (q, J = 7.2 Hz, 2 H), 2.27 (q, J = 7.6 Hz, 2 H), 2.32-2.48 (m, 2 H), 6.18 (t, J = 7.6 Hz, 1 H), 8.04 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 13.5, 13.7, 19.1, 22.5, 29.7, 30.6, 57.1, 141.0, 148.1, 166.0. HRMS: m/z [M + Na⁺] calcd for C₁₂H₂₃NNaOS: 252.1393; found: 252.1397.
Data for (S)-8c: [a]²⁰ _D +131.9 (c = 1.0, CHC1₃). ¹H NMR (400 MHz, CDCl₃): δ = 0.98 (s, 9 H), 2.68-2.81 (m, 4 H), 3.72 (dd, J ₁ = 27.6 Hz, J ₂ = 14.8 Hz, 2 H), 6.45 (t, J = 6.8 Hz, 1 H), 7.05-7.31 (m, 10 H), 8.10 (s, 1 H). ¹³C NMR (100 MHz, CDCl): δ = 22.2, 31.0, 31.6, 34.8, 57.1, 125.9, 126.2, 128.1, 128.2, 128.4, 128.5, 138.3, 139.3, 140.6, 148.2, 165.4. HRMS: m/z [M + Na⁺] calcd for C₂₂H₂₇NNaOS: 376.1706; found: 376.1704.
Data for 8d (major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 1.20 (s, 9 H), 1.78-1.87 (m, 2 H), 2.03 (s, 3 H), 2.07 (s, 3 H), 2.40-2.46 (m, 2 H), 2.70-2.80 (m, 2 H), 4.05-4.18 (m, 4 H), 6.34 (t, J = 7.6 Hz, 1 H), 8.10 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 20.9, 22.5, 24.2, 25.5, 27.9, 29.7, 57.3, 62.6, 63.6, 135.5, 149.1, 165.5, 170.7, 171.1. HRMS: m/z [M + H⁺] calcd for C₁₆H₂₈NO₅S: 346.1682; found: 346.1685.
Data for 8e (major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 1.15 (s, 9 H), 1.72-1.82 (m, 2 H), 2.42-2.50 (m, 2 H), 2.70-2.84 (m, 2 H), 3.44-3.54 (m, 4 H), 4.47 (s, 2 H), 4.48 (s, 2 H), 6.30 (t, J = 7.6 Hz, 1 H), 7.24-7.38 (m, 10 H), 8.06 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 22.4, 25.8, 26.5, 26.7, 57.0, 68.4, 69.2, 72.5, 72.6, 127.4, 127.5, 126.2, 126.3, 135.7, 138.3, 149.8, 165.7. HRMS: m/z [M + H⁺] calcd for C₂₆H₃₆NOS: 442.2410; found: 442.2422.
Data for 4g (major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 1.55-1.70 (m, 6 H), 2.30-2.42 (m, 4 H), 3.42-3.51 (m, 4 H), 4.48 (s, 2 H), 4.49 (s, 2 H), 6.47 (t, J = 7.6 Hz, 1 H), 7.25-7.36 (m, 10 H), 9.36 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 20.7, 25.4, 26.5, 26.6, 26.7, 29.4, 69.7, 69.8, 72.8, 72.9, 127.4, 127.5, 127.6, 128.3, 128.4, 138.4, 138.5, 143.2, 155.3, 195.1. HRMS: m/z [M + Na⁺] calcd for C₂₄H₃₀NaO₃: 389.2087; found: 389.2089.
Data for 4h (major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 1.38-1.57 (m, 6 H), 1.57-1.70 (m, 4 H), 2.25 (t, J = 7.6 Hz, 2 H), 2.34 (q, J = 7.2 Hz, 2 H), 3.42-3.50 (m, 4 H), 4.48 (s, 2 H), 4.50 (s, 2 H), 6.43 (t, J = 7.6 Hz, 1 H), 7.24-7.38 (m, 10 H), 9.35 (s, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 23.7, 25.3, 26.0, 28.5, 28.7, 29.5, 29.6, 70.1, 72.8, 76.4, 77.0, 77.7, 127.4, 127.5, 127.6, 128.3, 128.4, 138.3, 138.4, 143.5, 155.3, 195.2. HRMS: m/z [M + Na⁺] calcd for C₂₆H₃₄NaO₃: 417.2400; found: 417.2388.
Data for 10 (Z major isomer): ¹H NMR (400 MHz, CDCl₃): δ = 0.98 (s, 9 H), 4.06 (dd, J ₁ = 19.6 Hz, J ₂ = 15.2 Hz, 2 H), 7.14-7.31 (m, 5 H), 7.41 (s, 1 H), 7.57 (d, J = 8.8 Hz, 2 H), 8.21 (d, J = 9.2 Hz, 2 H), 8.36 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 22.3, 32.6, 57.8, 123.9, 126.4, 127.9, 128.7, 129.9, 138.2, 140.3, 141.6, 142.2, 147.6, 165.0. HRMS: m/z [M + Na⁺] calcd for C₂₀H₂₂N₂NaO₃S: 393.1243; found: 393.1235. Data for 10 (E minor isomer): ¹H NMR (400 MHz, CDCl₃): δ = 0.98 (s, 9 H), 4.16 (dd, J ₁ = 24.8 Hz, J ₂ = 16.4 Hz, 2 H), 7.35 (d, J = 8.4 Hz, 2 H), 7.38-7.42 (m, 5 H), 7.46 (s, 1 H), 8.14 (d, J = 8.8 Hz, 2 H), 8.36 (s, 1 H).

10

Representative Procedure of Grignard Addition to 8c: To a solution of 8c (1 mmol) in anhyd CH₂Cl₂ (10 mL) at 0 °C was added Grignard reagent (3 equiv). After being stirred for 1-5 h, the mixture was poured into sat. NH₄Cl solution, and the solution was extracted with CH₂Cl₂. The combined organic phases were dried with Na₂SO₄. After removing the solvent, the residue was subjected to chromatography to give allyl amine 11. The dr was determined by ¹H NMR analysis of crude 11. The absolute configuration of amine in 11 was not determined due to lack of comparable rotation data of structurally similar chiral amine.
Data for 11a (major isomer): [α]²⁰ _D +11.9 (c = 1.0, CHC1₃). ¹H NMR (400 MHz, CDCl₃): δ = 1.14 (s, 9 H), 2.32 (s, 3 H), 2.43-2.50 (m, 2 H), 2.71 (t, J = 7.6 Hz, 2 H), 3.10 (d, J = 15.6 Hz, 1 H), 3.26 (d, J = 4.0 Hz, 1 H), 3.40 (d, J = 15.6 Hz, 1 H), 4.82 (d, J = 4.0 Hz, 1 H), 5.89 (t, J = 7.2 Hz, 1 H), 6.94 (d, J = 6.8 Hz, 2 H), 7.09-7.30 (m, 12 H). ¹³C NMR (50 MHz, CDCl₃): δ = 21.1, 22.6, 30.0, 34.1, 35.7, 55.7, 63.1, 125.7, 125.9, 127.5, 128.3, 128.3, 128.5, 129.2, 129.5, 137.4, 137.8, 138.1, 139.3, 141.6. HRMS: m/z [M + H⁺] calcd for C₂₉H₃₆NOS: 446.2512; found: 446.2521.
Date for 11b (major isomer): [α]²⁰ _D +33.5 (c = 1.0, CHC1₃). ¹H NMR (400 MHz, CDCl₃): δ = 1.15 (s, 9 H), 1.28 (s, 3 H), 2.42-2.48 (m, 2 H), 2.73 (t, J = 7.6 Hz, 2 H), 2.91 (d, J = 5.6 Hz, 1 H), 3.41 (dd, J ₁ = 23.2 Hz, J ₂ = 15.6 Hz, 2 H), 3.88 (m, 1 H), 5.73 (t, J = 7.6 Hz, 1 H), 7.08 (d, J = 7.2 Hz, 2 H), 7.16-7.35 (m, 8 H). ¹³C NMR (50 MHz, CDCl₃): δ = 22.4, 22.6, 30.2, 33.4, 35.7, 55.5, 56.8, 125.9, 126.0, 128.3, 128.4, 128.5, 139.1, 139.7, 141.7. HRMS: m/z [M + H⁺] calcd for C₂₃H₃₂NOS: 370.2199; found: 370.2210.
Date for 11c (major isomer): [α]²⁰ _D +34.0 (c = 1.0, CHC1₃). ¹H NMR (400 MHz, CDCl₃): δ = 0.77 (d, J = 6.8 Hz, 3 H), 0.90 (d, J = 6.8 Hz, 3 H), 1.07 (s, 9 H), 1.70-1.74 (m, 1 H), 2.44-2.50 (m, 2 H), 2.68-2.72 (m, 2 H), 3.12 (d, J = 3.6 Hz, 1 H), 3.31-3.41 (m, 2 H), 3.43-3.44 (m, 1 H), 5.63 (t, J = 7.2 Hz, 1 H), 7.10-7.28 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.6, 20.0, 22.3, 30.2, 30.9, 33.7, 35.6, 55.2, 67.3, 76.5, 76.8, 77.2, 125.7, 125.8, 128.1, 128.3, 128.5, 130.7, 136.5, 139.4, 141.5. HRMS: m/z [M + Na⁺] calcd for C₂₅H₃₅NNaOS: 420.2332; found: 420.2337.
Date for 11d (major isomer): [α]²⁰ _D +15.3 (c = 1.0, CHC1₃). ¹H NMR (400 MHz, CDCl₃): δ = 0.92 (s, 9 H), 1.07 (s, 9 H), 2.32-2.42 (m, 2 H), 2.65 (t, J = 8.0 Hz, 2 H), 3.24-3.28 (m, 2 H), 3.56-3.60 (m, 2 H), 5.63 (t, J = 7.2 Hz, 1 H), 7.10 (d, J = 6.8 Hz, 2 H), 7.14-7.30 (m, 8 H). ¹³C NMR (100 MHz, CDCl₃): δ = 22.3, 27.2, 29.5, 30.4, 35.4, 36.0, 55.2, 68.1, 125.6, 128.0, 128.1, 128.2, 128.6, 132.4, 139.1, 141.5. HRMS: [M + H⁺] calcd for C₂₆H₃₈NOS: 412.2669; found: 412.2653.