(E)-1,1,1-Trifluoro-6,6-bis(4-methoxyphenyl)hexa-3,5-dien-2-one

Abstract

The title compound was obtained in high yield (84%) via the deacetylation of 3-(3,3-bis(4-methoxyphenyl)allylidene)-1,1,1,5,5,5-hexafluoro-2,4-pentanedione with K₂CO₃ in refluxing methanol. This previously unreported compound has been fully characterized by ¹⁹F{¹H}, ¹H and ¹³C{¹H} NMR, IR, UV-Vis, and HRMS.

1. Introduction

Trifluoromethyl ketones represent a fascinating class of molecules with application in a wide range of fields [1]. In particular, taking advantage of the activating effect of the trifluoroacetyl group on the conjugated C=C bond, trifluoromethyl enones R¹R²C=C(R³)C(=O)CF₃ have been extensively employed for the construction of 3- to 7-membered fluorinated heterocycles through different cycloaddition processes [2,3,4,5]. On the contrary, despite their enormous synthetic potential, the chemistry of related trifluoromethyl dienones has been comparatively much less developed due to their more difficult access [6,7,8,9].

In the context of our studies on the preparation of conjugated diene-dione derivatives by metal-catalyzed dehydrative couplings between propargylic alcohols and β-diketones [10,11,12,13], we reported a few years ago the synthesis and structural characterization of the push-pull dye 3-(3,3-bis(4-methoxyphenyl)allylidene)-1,1,1,5,5,5-hexafluoro-2,4-pentanedione (3), which showed remarkable solvatochromic properties, through the coupling of 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol (1) with 1,1,1,5,5,5-hexafluoropentanedione (2) (Scheme 1) [11]. The formation of 3 involves the initial Meyer–Schuster rearrangement of propargylic alcohol 1, catalyzed by the allyl-ruthenium(II) complex [Ru(η³-2-C₃H₄Me)(CO)(dppf)][SbF₆] (dppf = 1,1′-bis(diphenylphosphino)ferrocene), and a subsequent Knoevenagel condensation of the resulting α,β-unsaturated aldehyde with the perfluorinated β-diketone 2. Herein, we describe that compound 3 can be easily deacetylated upon treatment with K₂CO₃ in refluxing methanol, leading to the novel trifluoromethyl dienone (E)-1,1,1-trifluoro-6,6-bis(4-methoxyphenyl)hexa-3,5-dien-2-one (4) in a completely stereoselective manner.

2. Results and Discussion

Base-promoted deacetylation reactions of β-diketones are well documented in the literature [14,15,16,17]. Accordingly, we found that the treatment of a methanolic solution of diene-dione 3 with an excess of K₂CO₃ (10 equiv.) under refluxing conditions leads to the clean formation of the dienone 4, which was isolated as a yellow oil in 84% yield after appropriate chromatographic work-up (Scheme 2). In the reaction, the volatile ester CF₃CO₂Me is also formed, as confirmed by recording the ¹⁹F{¹H} NMR spectrum of the reaction mixture prior to vacuum evaporation. Thus, in addition to the signal of compound 4 (a singlet a δ_F −77.3 ppm), a second singlet at δ_F −75.7 ppm [18] was present in the spectrum.

Compound 4 was characterized by means of HRMS, IR, and multinuclear NMR spectroscopy, the data obtained being fully in accord with the proposed formulation (details are given in the Materials and Methods section; copies of the NMR spectra are provided as Supplementary Materials). In this regard, key spectroscopic features are the following: (i) (IR) the presence of a characteristic absorption band at 1699 cm⁻¹ for the carbonyl group, (ii) (¹H NMR) typical signals for the olefinic protons of the butadiene chain at δ_H 6.59 (d, ³J_HH = 15.0 Hz), 6.82 (d, ³J_HH = 11.7 Hz), and 7.75 (dd, ³J_HH = 15.0 and 11.7 Hz) ppm, with the coupling constant of 15.0 Hz confirming the E stereochemistry of the CH=CH bond, and (iii) (¹³C{¹H} NMR) characteristic quartet resonances for the CF₃ and C=O carbons at δ_C 116.6 (¹J_CF = 291.0 Hz) and 179.9 (²J_CF = 34.6 Hz) ppm, respectively. On the other hand, as previously observed for 3, the UV-Vis spectrum of 4 in CH₂Cl₂ also displayed an intense absorption band in the visible region (λ_max = 406 nm; Figure 1).

Compared to 3, a large hypsochromic shift (Δλ_max = −41 nm), as a consequence of the replacement of one of the electron-acceptor trifluoroacetyl groups by hydrogen, is observed. Finally, it is also worth mentioning that the trifluoromethyl dienone 4 also features a solvatochromic behavior, its absorption maximum undergoing a red shift by increasing the solvent polarity, i.e., λ_max changes from 389 to 410 nm on going from hexane to N,N-dimethylformide (DMF). However, the bathochromic shift of the absorption band observed for 4 (Δλ_max = 21 nm) is smaller in comparison to that of parent diene-dione 3 (Δλ_max = 42 nm when going from hexane to DMF) [11].

3. Materials and Methods

The diene-dione 3 was synthesized as described in the literature [11]. NMR measurements (all the spectra were recorded at room temperature) were performed with a Bruker DPX-300 instrument (Billerica, MA, USA). The chemical shift values (δ) are given in part per million and are referred to the residual peak of the deuterated solvent that was employed (¹H and ¹³C) or to the CFCl₃ standard (¹⁹F). The PerkinElmer 1720-XFT and Lambda 25 spectrometers (Waltham, MA, USA) were employed for IR and UV-Vis measurements, respectively. HRMS data (QTOF Bruker Impact II mass spectrometer) were provided by the General Services of the University of Oviedo). Merck silica gel 60 (230–400 mesh) was employed for the chromatographic work-up.

(E)-1,1,1-Trifluoro-6,6-bis(4-methoxyphenyl)hexa-3,5-dien-2-one (4)

To a solution of compound 3 (0.230 g, 0.5 mmol) in methanol (15 mL), K₂CO₃ (0.691 g, 5 mmol) was added, and the resulting mixture heated under reflux for 4 h. A color change from orange to yellow was observed. After elimination of the volatiles under vacuum, the oily residue was purified by column chromatography using a mixture EtOAc/hexane (1:10 v/v) as eluent. Compound 4 was isolated as a yellow oil in 84% yield (0.152 g). The characterization data for 4 are as follows: ¹⁹F{¹H} NMR (282 MHz, CDCl₃): δ = −77.3 (s) ppm. ¹H NMR (300 MHz, CDCl₃): δ = 7.75 (dd, 1H, ³J_HH = 15.0 and 11.7 Hz, CH=CHC(=O)CF₃), 7.32, 7.17, 6.98 and 6.90 (d, 2H each, ³J_HH = 8.7 Hz, CH_arom), 6.82 (d, 1H, ³J_HH = 11.7 Hz, CH=CH=CHC(=O)CF₃), 6.59 (d, 1H, ³J_HH = 15.0 Hz, =CHC(=O)CF₃), 3.90 and 3.86 (s, 3H each, OMe) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 179.9 (q, ²J_CF = 34.6 Hz, C=O), 161.1, 160.5 and 148.7 (2C) (s, C_arom), 157.0 (s, =C), 133.5, 123.2, 118.0 (s, =CH), 132.1, 130.4, 113.9 and 113.8 (s, CH_arom), 116.6 (q, ¹J_CF = 291.0 Hz, CF₃), 55.4 and 55.3 (s, OMe) ppm. IR (neat): ν = 3006 (w), 2959 (w), 2934 (w), 2839 (w), 1699 (m), 1603 (s), 1562 (s), 1511 (s), 1463 (m), 1420 (w), 1341 (w), 1287 (m), 1253 (s), 1195 (s), 1173 (s), 1140 (s), 1121 (m), 1059 (s), 1032 (s), 992 (w), 913 (w), 857 (m), 837 (m), 806 (w), 734 (w), 837 (m), 806 (w), 734 (w), 721 (m), 601 (m) cm⁻¹. UV-vis (CH₂Cl₂): λ_max 406 nm (ε 20,850 M⁻¹ cm⁻¹). HRMS (ESI): m/z 363.120281, [M + H⁺] (calcd. for C₂₀H₁₈F₃O₃: 363.120256).

4. Conclusions

In summary, a novel trifluoromethyl dienone has been synthesized in high yield and in a complete stereoselective manner through a deacetylation procedure, a route of access scarcely applied to date to obtain this type of fluorinated molecules [19].