Mild and Metal-Free Regioselective 1,2-Addition of Carbon Nucleophiles to α,β-Unsaturated Imines

Abstract

A mild and metal-free regioselective 1,2-addition of carbon nucleophiles to α,β-unsaturated imines has been developed. Good yields and total regioselectivities were achieved by addition of p-nitrobenzyl chloride or 2,3-bis(bromomethyl)quinoxaline to α,β-unsaturated tosylimines.

Key words

α,β-unsaturated tosylimines - regioselectivity - TDAE - addition - metal-free

• References and Notes

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• 6 General Procedure To a stirred solution of p-nitrobenzyl chloride (1) or 2,3-bis(bromomethyl)quinoxaline (4, 0.2 mmol) and N-tosylimine 2 (0.24 mmol) in DMF (1 mL) at –20 °C was added TDAE (0.2 mmol). The solution was vigorously stirred at –20 °C for 1 h and then maintained at r.t. for 2 h. Water (5 mL) was added, and the aqueous solution was extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were washed with H₂O (20 mL) and dried over MgSO₄. Filtration and evaporation of the solvent furnished the crude product. Purification by silica gel chromatography (PE–EtOAc from 8:2 to 7:3 depending on the polarity of substrate) afforded pure amine products 3 or 5. (E)-4-Methyl-N-(1-(4-nitrophenyl)-4-phenylbut-3-en-2-yl)benzenesulfonamide (3a) 81% yield; yellow solid; mp 189–191 °C. ¹H NMR (250 MHz, CDCl₃): δ = 8.04 (d, J = 8.5 Hz, 2 H), 7.60 (d, J = 8.1 Hz, 2 H), 7.26–7.12 (m, 9 H), 6.24 (d, J = 15.9 Hz, 1 H), 5.85 (dd, J = 15.9, 7.0 Hz, 1 H), 4.75 (d, J = 7.9 Hz, 1 H), 4.29–4.18 (m, 1 H), 3.03–2.98 (m, 2 H), 2.31 (s, 3 H). ¹³C NMR (63 MHz, CDCl₃): δ = 147.0, 144.4, 143.8, 137.6, 135.8, 132.5, 130.5, 129.7, 128.7, 128.3, 127.4, 127.2, 126.6, 123.8, 56.9, 42.3, 21.5. ESI-HRMS: m/z [M + NH₄]⁺ calcd for [C₂₃H₂₆N₃O₄S]⁺: 440.1639; found: 440.1640. (E)-3-Styryl-2-tosyl-1,2,3,4-tetrahydropyrido[3,4-b]quinoxaline (5a) 61% yield; yellow solid; mp 72–75 °C. ¹H NMR (250 MHz, CDCl₃): δ = 8.02–7.95 (m, 2 H), 7.79 (d, J = 8.2 Hz, 2 H), 7.75–7.71 (m, 2 H), 7.22–7.16 (m, 5 H), 7.05–7.01 (m, 2 H), 6.38 (d, J = 16.1 Hz, 1 H), 5.86 (dd, J = 16.1, 5.5 Hz, 1 H), 5.32 (br s, 1 H), 5.12 (d, J = 17.6 Hz, 1 H), 4.50 (d, J = 17.6 Hz, 1 H), 3.55 (dd, J = 17.3, 5.9 Hz, 1 H), 3.38 (dd, J = 17.3, 2.0 Hz, 1 H), 2.34 (s, 3 H). ¹³C NMR (63 MHz, CDCl₃): δ = 149.4, 148.0, 144.1, 141.9, 141.4, 136.3, 135.7, 134.2, 130.1, 130.0, 128.8, 128.7, 128.6, 128.3, 127.7, 126.6, 124.6, 53.4, 46.4, 36.9, 21.6 (one carbon missing due to overlap). ESI-HRMS: m/z [M + H]⁺ calcd for [C₂₆H₂₄N₃O₂S]⁺: 442.1584; found: 442.1584.
• 7 CCDC 1413021 contains the supplementary crystallographic data of compound 3a for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via http://www.ccdc.cam.ac.uk/data_request/cif.
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