An Efficient One-Pot Two-Step Three-Component Process for the Synthesis of Trifluoromethylated Hydrochromenes

Abstract

Unless otherwise noted, all reagents were purchased from commercial sources and used without further purification. Methyl 4,4,4-trifluorobut-2-ynoate 1 were prepared according to the known literatures. 1 Solvents were distilled before use. Melting points were recorded on a SGW X 4 instrument and uncorrected. 1 H, 19 F and 13 C NMR spectra were recorded on a Bruker DRX-500MHz spectrometer. All chemical shifts are reported in parts per million downfield (positive) of the standard: CFCl 3 for 19 F, TMS for 1 H and 13 C NMR spectra. IR spectra were obtained on an AVATAR370 FT-IR spectrometer. LRMS (lower resolution mass spectra) was obtained on Thermo LTQ FTMS or APEX-III and HRMS (high resolution mass spectra) on Bruker Daltonics, Inc. APEXIII 7.0 TESLA FTMS, or Thermo Fisher Scientific LTQ FT Ultra instruments, respectively. X-ray analysis was performed on a Bruker Smart Apex2 CCD spectrometer. Yields reported in this publication refer to isolated ones of compounds and their purity was determined by 1 H NMR. General procedure for the synthesis of 7a: The mixture of dimedone 2 (2.0 mmol), benzaldehydes 3a (1.0 mmol), piperidine (0.25 mmol) was stirred in EtOH (5 mL) at room temperature for 2 h. Upon the completion of the reaction, the solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluting with petroleum ether / ethyl acetate 1:1, v:v) to give product 7a. 7a 2,2'-(Phenylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) 7a: White