A One-Pot Stereoselective Synthesis of Electron-Deficient 4-Substituted (E,E)-1-Arylsulfonylbuta-1,3-dienes and Their Chemoselective [3+2] Cycloaddition with Azomethine Ylides – A Simple Synthesis of 1,3,4-Trisubstituted Pyrrolidines and Pyrroles

Abstract

A simple and efficient method for the synthesis of (E,E)-1-(arylsulfonyl)buta-1,3-dienes bearing electron-withdrawing substituents like cyano and ethoxycarbonyl at position 4, involving a one-pot alkylation of bis(phenylsulfonyl)methane with trans-ethyl 4-bromocrotonate/trans-4-bromocrotononitrile, and elimination of arylsulfinic acid, is described. These dienes undergo facile mono [3+2] cycloaddition with azomethine ylides chemoselectivity to furnish functionalized 1,3,4-trisubstituted pyrrolidines. Oxidation of these cycloadduct with MnO₂·SiO₂ under mild conditions provides 1,3,4-trisubstituted pyrroles.

Key words

(E,E)-1-arylsulfonylbuta-1,3-diene - azomethine ylide - chemoselective cycloaddition - 1,3,4-trisubstituted pyrrolidines - 1,3,4-trisubstituted pyrroles

• References and Notes


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• 25 General Procedure for the Synthesis of (3S,4R)-Ethyl 1-tert-Butyl-4-[(E)-2-(phenylsulfonyl)vinyl]pyrrolidine-3-carboxylate (8a) TFA (0.38 mmol) in CH₂Cl₂ (1 mL) was added to a stirred solution of (E,E)-1-arylsulfonyl-4-ethoxycarbonylbuta-1,3-diene (4a, 3.8 mmol) and N-(methoxymethyl)-N-[(trimethylsilyl)methyl]tert-butylamine (7a, 4.7 mmol) in anhyd CH₂Cl₂ (15 mL) at 0 °C under N₂ atmosphere, the reaction mixture was allowed to warm to r.t. and stirred for 30 min. After completion of reaction (monitored by TLC), the reaction mixture was quenched with a 10% aq solution of NaHCO₃ (30 mL) and extracted with CH₂Cl₂ (2 × 30 mL), washed with H₂O (30 mL) and brine (30 mL), and the organic layer was dried over MgSO₄. The solvent was evaporated under vacuum, and the crude product was subjected to column chromatography (25% EtOAc in n-hexane) to yield analytically pure (3S,4R)-ethyl 1-tert-butyl-4-[(E)-2-(phenylsulfonyl)vinyl]pyrrolidine-3-carboxylate (8a) as a pale yellow gummy liquid; yield 76%. ¹H NMR (400 MHz, CDCl₃): δ = 7.79 (m, 2 H), 7.45–7.57 (m, 3 H), 6.89 (dd, 1 H, J = 15.0 Hz), 6.30 (d, 1 H, J = 15.8 Hz), 4.01 (q, 1 H, J = 7.2 Hz), 3.08 (m, 1 H), 2.96 (t, 1 H, J = 8.8 Hz), 2.87 (t, 1 H, J = 8.7 Hz), 2.80 (t, 1 H, J = 7.5 Hz), 2.72 (q, 1 H, J = 7.8 Hz), 2.55 (t, 1 H, J = 7.7 Hz), 1.18 (t, 3 H, J = 7.1 Hz), 1.08 (s, 9 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 172.85, 146.98, 140.37, 133.28, 130.75, 129.19, 127.54, 60.90, 52.37, 51.14, 49.06, 48.15, 43.04, 25.75, 14.02 ppm. DEPT-NMR (100 MHz, CDCl₃): δ = 133.80, 133.42, 128.97, 128.80, 125.31, 121.68, 60.23, 30.37, 14.42 ppm. LC–MS (EI): m/z = 366.1 [M + 1]. Anal. Calcd for C₁₉H₂₇NO₄S: C, 62.44; H, 7.45; S, 8.77; N, 3.83. Found: C, 62.53; H, 7.37; S, 8.92; N, 3.93
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• 30 General Procedure for the Synthesis of Ethyl 1-tert-Butyl-4-[(E)-2-(phenylsulfonyl)vinyl]-1H-pyrrole-3-carboxylate (10a) Activated MnO₂ on silica (13.7 mol, freshly prepared) was added to a stirred solution of ethyl 1-tert-butyl-4-[(E)-2-(phenylsulfonyl)vinyl]pyrrolidine-3-carboxylate (8a, 2.74 mol) in anhyd 1,4-dioxane (20 mL) under argon. After being stirred at reflux for 5 h (monitored by TLC), the reaction mixture was filtered through a pad of Celite, and the pad was washed with 1,4-dioxane. Evaporation of the filtrate under vacuum furnished the crude product, which was subjected to column chromatography (25% EtOAc in n-hexane) to yield analytically pure ethyl 1-tert-butyl-4-[(E)-2-(phenylsulfonyl)-vinyl]-1H-pyrrole-3-carboxylate (10a) as a pale yellow gummy liquid in 68% yield. ¹H NMR (400 MHz, CDCl₃): δ = 8.02 (d, 1 H, J = 15.4 Hz), 7.93 (m, 2 H), 7.51 (m, 4 H), 7.11 (s, 1 H), 6.98 (d, 1 H, J = 15.4 Hz), 4.26 (q, 2 H), 1.38 (s, 9 H), 1.34 (t, 3 H) ppm. ¹³C NMR (400 MHz, CDCl₃): δ = 164.13, 138.47, 133.73, 133.34, 128.89, 128.73, 125.23, 121.60, 116.08, 116.04, 60.15, 56.78, 30.29, 14.36 ppm. LC–MS (EI): m/z = 384.4 [M⁺ + Na]. Anal. Calcd for C₁₉H₂₃NO₄S: C, 63.13; H, 6.41; S, 8.87; N, 3.88. Found: C, 63.47; H, 6.47; S, 8.52; N, 3.68