Palladium-Catalyzed Coupling of Pyrid-4-yl Nonaflates with Methyl Diazoacetate

Abstract

Palladium-catalyzed couplings of pyrid-4-yl nonaflates with methyl diazoacetate are described. After optimization of the reaction conditions the scope of the transformation proved to be fairly broad and a series of pyrid-4-yl-substituted methyl diazoacetates was prepared in generally high yields.

Key words

pyridines - bipyridines - nonaflates - palladium catalysis - cross couplings - diazoacetate

• References and Notes

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• 13 Palladium-Catalyzed Coupling of Pyrid-4-yl Nonaflates with Methyl Diazoacetate; Typical Procedure for 14a: A sealed tube equipped with a stirring bar was charged with Pd(PPh₃)₄ (40 mg, 0.034 mmol) and pyrid-4-yl nonaflate 13a ^11c (210 mg, 0.34 mmol). MeCN (3.5 mL), Et₃N (71 μL, 0.51 mmol) and methyl diazoacetate (100 mg, 1.00 mmol) were added and the resulting solution was stirred at 45 °C for 4 h until complete conversion of the starting material was observed (reaction monitored by TLC). H₂O (20 mL) and EtOAc (20 mL) were added and the organic layer was separated. The aqueous layer was extracted with EtOAc (3 × 20 mL) and the combined organic layers were dried with Na₂SO₄, filtered, and the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography on silica gel (hexane–EtOAc, 4:1) to provide pyridyl diazoacetate 14a (101 mg, 72%) as a yellow oil. [α]_D –63.5 (c = 1.0, CHCl₃). IR (ATR): 3090–2860 (C-H), 2095 (CN₂), 1715 (C=O), 1595–1550 (C=C) cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.00, 0.93 (2 × s, 6 H + 9 H, OTBS), 2.49 (s, 3 H, Me), 3.86 (s, 3 H, CO₂CH₃), 5.83 (s, 1 H, CHPh), 7.17–7.20, 7.25–7.29, 7.37–7.38, 7.47–7.49 (4 × m, 1 H + 3 H + 1 H + 2 H, Ph, 3-H/5-H). ¹³C NMR (126 MHz, CDCl₃): δ = –4.93, –4.91, 18.2, 25.7 (2 × q + s + q, OTBS), 24.6 (q, Me), 52.1 (q, CO₂ CH₃), 77.5 (d, CHPh), 110.3, 115.5 (2 × d, C-3/C-5), 126.2, 127.0, 128.0 (3 × d, Ph), 128.2, 136.0, 143.7, 157.6 (4 × s, Ph, C-2/C-4/C-5), 164.3 (s, CO); the signal for C=N₂ was not detected. HRMS (ESI-TOF): m/z [M + H]⁺ calcd. for C₂₂H₃₀N₃O₃Si: 412.2051; found: 412.2039
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