Selective 7-endo-Cyclization of 3-Aza-5-alkenols through Oxidative Pd(II)-Catalyzed Olefin Oxyarylation

Abstract

3-Aza-5-alkenols undergo selective 7-endo-trig cyclization when treated with a catalytic Pd(II) species, CuCl₂ and ArSnBu₃ giving 7-aryl-substituted oxazepanes. The intramolecular alkoxylation occurs with formation of a seven-membered ring only when associated with an arylating step. Otherwise, 6-exo-trig reactions, providing morpholine derivatives, were observed.

Key words

palladium - heterocycles - domino reactions - Wacker reaction - homogeneous catalysis - cyclization - oxyarylation

• References and Notes

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• 12 General Procedure for the 7-endo-trig Oxyarylation process A mixture of N-allylaminoalcohol 1 (1.0 equiv), PdCl₂(CH₃CN)₂ (0.1 equiv), CuCl₂ (1.0 equiv), and PhSnBu₃ (1.0 equiv) in THF (0.2 M) was stirred at room temperature for 18–24 h. Then the solvent was evaporated under reduced pressure, and water (10 mL) was added. The aqueous layer was extracted with CH₂Cl₂ (3 × 10 mL), and the organic layers were dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by silica column chromatography to afford the corresponding oxazepane 3.
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• 20 Spectroscopic Data of 7-[4-(Benzyloxy)phenyl]-4-(4-methylbenzenesulfonyl)-1,4-oxazepane (10) ¹H NMR (400 MHz, CDCl₃): δ = 1.93–1.99 (m, 1 H), 2.16–2.21 (m, 1 H), 2.37 (s, 3 H), 3.15–3.19 (m, 1 H), 3.23–3.29 (m, 1 H), 3.48–3.54 (m, 1 H), 3.58–3.70 (m, 2 H), 3.99 (dt, J = 12.8, 2.9 Hz, 1 H), 4.54 (dd, J = 5.6, 9.6 Hz, 1 H), 4.97 (s, 2 H), 6.85 (d, J = 8.1 Hz, 2 H), 7.12 (d, J = 8.1 Hz, 2 H), 7.24–7.35 (m, 7 H), 7.63 (d, J = 8.1 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.5 (q), 37.6 (t), 46.2 (t), 51.7 (t), 69.8 (t), 70.0 (t), 81.1 (d), 114.8 (d), 126.9 (d), 127.0 (d), 127.4 (d), 127.9 (d), 128.6 (d), 129.8 (d), 135.3 (s), 135.9 (s), 136.9 (s), 143.4 (s), 158.1 (s). MS: m/z = 437 [M⁺]. Anal. Calcd for C₂₅H₂₇NO₄S: C, 68.63; H, 6.22; N, 3.20. Found: C, 68.74; H, 5.98; N, 3.47.
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