Copper-Catalyzed Oxidative ipso-Cyclization of N-(p-Methoxyaryl)propiolamides with Disulfides and Water Leading to 3-(Arylthio)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-diones

Abstract

A new copper-catalyzed oxidative ipso-cyclization of N-(p-methoxyaryl)propiolamides with disulfides for the synthesis of 3-(arylthio)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-diones has been developed. This method proceeds via sequential oxidative C–S bond formation, ipso-cyclization, and dearomatization and provides a new facile oxidative strategy to assemble the target products using an inexpensive catalytic system comprising copper(II) chloride and molecular oxygen.

Key words

copper - cyclization - N-(p-methoxyaryl)propiolamides - disulfides - 3-(arylthio)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-diones

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• 8 Copper-Catalyzed Oxidative ispo-Cyclization to 3-(Arylthio)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-diones; Typical Procedure To a Schlenk tube were added N-(p-methoxyaryl)propiolamide 1a (0.2 mmol), 1,2-diphenyldisulfane (2a, 1.5 equiv), H₂O (2 equiv), CuCl₂ (10 mol%), and DMF (anhydrous; 2 mL). Then the tube was charged with oxygen and was stirred at 100 °C for 24 h until complete consumption of starting material as monitored by TLC and/or GC–MS analysis. After the reaction was finished, the reaction mixture was washed with brine. The aqueous phase was re-extracted with EtOAc. The combined organic extracts were dried over Na₂SO₄, concentrated in vacuum, and the resulting residue was purified by silica gel column chromatography (hexane–EtOAc) to afford the desired product 3aa. 1-Methyl-4-phenyl-3-(phenylthio)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione (3aa) Yellow solid; mp 157.6–159.4 °C (uncorrected). ¹H NMR (400 MHz, CDCl₃): δ = 7.29–7.17 (m, 10 H), 6.54 (d, J = 8.8 Hz, 2H), 6.47 (d, J = 8.8 Hz, 2 H), 2.89 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 183.9, 167.6, 152.7, 145.1, 133.1, 132.1, 131.6, 130.9, 130.6, 129.6, 128.9, 128.2, 128.0, 127.4, 67.7, 26.2. IR (KBr): 1700, 1664 cm^–1. ESI-HRMS: m/z calcd for C₂₂H₁₇NO₂S [M + H]⁺: 360.1053; found: 360.1058