Palladium-Catalysed Cyclisation-Anion Capture Processes: In situ ‘Zipper’ Generation via Intramolecular Nucleophilic Capture of π-Allylpalladium Species

Abstract

A palladium-catalysed one-pot reaction for the in situ generation of ‘zippers’ and subsequent cyclisation-anion capture with phenyl boronic acid produces tricyclic heterocycles with the formation of three C-C bonds, one C-N bond, two rings, two ste­reocentres and one tetrasubstituted C-centre.

Key words

organopalladium chemistry - one-pot sequential reaction - heterocycles

References and Notes

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14

Compound 2b: A mixture of 1b (1 mmol), Cs₂CO₃ (3 mmol), Pd(Ph₃)₄ (10 mol%), and 2-iodothiophene (1 mmol) in toluene (10 mL) was stirred and heated at 70 °C for 16 h at which stage phenyl boronic acid (1 mmol) was added. The mixture was heated at 110 °C for 22 h, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash chromatography, (petroleum ether-Et₂O, 1:3), to give the product in 64% yield as a single diastereomer, which crystallised from (EtOH-H₂O) as colourless prisms; mp 170-171 °C. IR (film): 2947, 1652 (CO), 1597, 1479,1462, 1428, 1402, 1284, 909 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 1.03 (qd, J = 13.2, 3.4 Hz, 1 H, HCHCHN), 1.62 (qdd, J = 13.2, 6.0, 3.2 Hz, 1 H, HCHCHN), 1.88 (m, 1 H, HCHCH₂C=O), 1.95 (m, 1 H, HCHCH₂C=O), 2.24 (m, 1 H, HCHC=O), 2.44 (ddt, J = 18.0, 5.9, 1.5 Hz, 1 H, HCHC=O), 3.62, 3.85 (2 × d, J = 14.2 Hz, 2 H, CH₂Ph), 4.08 (dd, J = 11.8, 3.7 Hz, 1 H, CHN), 6.47 (dd, J = 3.6, 1.1 Hz, 1 H, thienyl-H), 6.91 (dd, J = 5.1, 3.6 Hz, 1 H, thienyl-H), 7.06-7.08 (m, 2 H, ArH), 7.14-7.25 (m, 5 H, ArH), 7.31 (td, J = 7.8, 1.3 Hz, 1 H, ArH), 7.34 (dd, J = 7.8, 1.3 Hz,1 H, ArH), 8.19 (d, J = 7.8 Hz, 1 H, ArH). ¹³C NMR (300 MHz, CDCl₃): δ = 20.70, 24.90, 32.70, 41.90, 54.70, 66.80, 118.10, 124.70, 125.00, 125.20, 125.80, 127.30, 127.40, 128.80, (2 × C), 129.20, 131.20 (2 × C), 135.90,137.10, 143.00, 148.60, 169.10. MS (FAB): m/z (%) = 360 (M⁺ + H, 100), 268 (86), 212 (7), 91 (11). Anal. Calcd for C₂₃H₂₁NOS: C, 76.85; H, 5.90; N, 3.90; S, 8.90. Found: C, 76.60; H, 5.80; N, 3.85; S, 8.80.