Synthesis of Spirocyclopropane Oxindoles via Michael-Initiated Cyclopropanation of Pyridinium Salts with 3-Ylidene Oxindoles

Abstract

A Michael-initiated ring-closure reaction of pyridinium salts with arylidene oxindoles has been developed. A wide range of aryl-substituted spirocyclopropane oxindoles has been achieved in moderate to good yields (41–99%). This efficient strategy exhibits good functional group compatibility and may serve as an attractive method for the synthesis of diverse cyclopropanes.

Key words

pyridinium salts - Michael - cyclopropanation - spirocyclopropane - oxindoles

Publication History

Received: 14 October 2020

Accepted after revision: 02 December 2020

Accepted Manuscript online:
02 December 2020

Article published online:
07 January 2021

• References and Notes

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• 12 Ethyl (2S*,3R*)-2′-Oxo-3-[4-(trifluoromethyl)phenyl]spiro [cyclopropane-1,3′-indoline]-2-carboxylate (3c) – Typical Procedure The solution of (E)-3-[4-(trifluoromethyl)benzylidene]indolin-2-one (145 mg, 0.5 mmol), ethoxycarbonylmethylpyridinium bromide (245 mg, 1.0 mmol) in dry DMF (4 mL) in the presence of Cs₂CO₃ (163 mg, 0.5 mmol) was stirred at 110 °C for 4 h. After completion of the reaction, the mixture was quenched by adding 10 mL of water at room temperature and extracted with EtOAc (3 × 10 mL). The combined organic phase was washed with H₂O (3 × 10 mL), dried over anhydrous Na₂SO₄, concentrated in vacuo, and purified with flash silica gel chromatography using EtOAc/hexane (1:5 to 1:3) to afford 3c (147 mg, 78%) as a white solid; mp 183–184 °C (petroleum ether/EtOAc); R_f = 0.50 (petroleum ether/EtOAc = 3:1). ¹H NMR (400 MHz, CDCl₃): δ = 8.72–8.54 (m, 1 H), 7.56 (d, J = 8.0 Hz, 2 H), 7.48 (d, J = 8.0 Hz, 1 H), 7.43 (d, J = 8.0 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 1 H), 7.06 (t, J = 8.0 Hz, 1 H), 6.80 (t, J = 8.0 Hz, 1 H), 4.29–4.15 (m, 2 H),3.81 (d, J = 8.0 Hz, 1 H), 3.36 (d, J = 8.0 Hz, 1 H), 1.27 (t, J = 8.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 173.6, 168.0, 141.2, 137.0, 129.6, 127.9, 126.1, 125.02, 124.99 122.8, 122.5 (J _C–F = 41 Hz), 122.4, 109.9, 61.8, 39.8, 39.3, 37.1, 14.1. HRMS (ES⁺–TOF): m/z calcd for C₂₀H₁₇F₃NO₃ ⁺ [M + H]⁺: 376.1155; found: 376.1166.
• 13 CCDC 2032994 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.