Synergistic Organoboron/Palladium Catalysis for Regioselective N-Allylation of 2-Pyridones, 4-Pyridones, and Related Ambident Heterocycles
Giorgos Yatzoglou
,
Matthew T. Zambri
,
Shrey P. Desai
,
Mark S. Taylor∗
This work was funded by Natural Sciences and Engineering Research Council of Canada (NSERC, Discovery Grant), the Canada Foundation for Innovation (projects 17545 and 19119), and the Ontario Research Foundation (Province of Ontario).
The use of a boronic acid co-catalyst along with a palladium complex enables efficient dehydrative couplings of allylic alcohols and tautomerizable heterocycles. The protocol has been applied to achieve N-allylations of 2-pyridones, 4-pyridones, 4-pyrimidinones, and their benzofused derivatives.
26General Protocol for N-Allylation: Synthesis of 1-Allylpyridin-4(1H)-one (3a)
Under an atmosphere of argon, an oven-dried two-dram vial equipped with a magnetic stir bar and rubber spectrum was charged with 4-pyridone (47.6 mg, 0.500 mmol, 1 equiv), [Pd(allyl)Cl]2 (1.8 mg, 0.0050 mmol, 1 mol%), Xantphos (5.8 mg, 0.010 mmol, 2 mol %), and 3,5-bis(trifluoromethyl)phenylboronic acid (1a, 25.8 mg, 0.100 mmol, 20 mol%). The vial was evacuated and backfilled with argon, then toluene (2.5 mL) and allyl alcohol (41 mL, 35 mg, 0.60 mmol, 1.2 equiv) were added sequentially by syringe. The vial was sealed with a cap, placed in an oil bath at 50 °C and stirred for 24 h. The mixture was cooled to room temperature, concentrated in vacuo, and purified by flash column chromatography on silica gel (95:5 CH2Cl2/MeOH), yielding 3a as a yellow oil in 97% yield (65.5 mg, 0.484 mmol).
Characterization Data for 3a1H NMR (500 MHz, CDCl3): δ = 7.25 (d, J = 7.7 Hz, 2 H), 6.30 (d, J = 7.7 Hz, 2 H), 5.87 (ddt, J = 17.0, 10.3, 5.7 Hz, 1 H), 5.37–5.11 (m, 2 H), 4.34 (d, J = 5.7 Hz, 2 H) ppm. 13C NMR (126 MHz, CDCl3): δ = 178.8, 139.9, 131.7, 119.9, 118.6, 58.7 ppm. IR (film): ν = 3082 (w), 1633 (s), 1538 (s), 1399 (m), 1181 (s), 940 (w), 850 (s) cm–1. HRMS (direct analysis in real time): m/z calcd for C8H10NO [M + H]+: 136.0755; found: 136.0757. Spectroscopic data were in agreement with those reported in the literature.13b For experimental protocols, characterization data, and copies of NMR spectra of all products shown in Schemes 2 and 3, see the Supporting Information.
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Dubovyk I,
Watson ID. G,
Yudin AK.
J. Org. Chem. 2013; 78: 1559
