Novel Fluorinated Indanone, Tetralone and Naphthone Derivatives: Synthesis and Unique Structural Features

Abstract

Several fluorinated and trifluoromethylated indanone, tetralone and naphthone derivatives have been prepared via Claisen condensations and selective fluorinations in yields ranging from 22-60%. In addition, we report the synthesis of new, selectively fluorinated bindones in yields ranging from 72-92%. Of particular interest is the fluorination and trifluoroacetylation regiochemistry observed in these fluorinated products. We also note unusual transformations including a novel one pot, dual trifluoroacetylation, trifluoroacetylnaphthone synthesis via a deacetylation as well as an acetyl-trifluoroacetyl group exchange. Solid-state structural features exhibited by these compounds were investigated using crystallographic methods. Crystallographic results, supported by spectroscopic data, show that trifluoroacetylated ketones prefer a chelated cis-enol form whereas fluorinated bindone products exist primarily as the cross-conjugated triketo form. OPEN ACCESSAppl. Sci. 2012, 2 62

Special Feature Organo-Fluorine Chemical Science

“…Joseph Sloop [16] [17] and coworkers illustrated that the predicted product outcomes from DFT calculations were consistent with the experimental data and mechanistic pathways to products when fluorinated dihydropyrans were reacted with aromatics. Fluorine-18, widely used in clinical positron emission tomography (PET) imaging in biomedical science because its optimal physical decay properties (t1/2 = 110 min, E β+, max = 0.6 MeV) facilitates multistep syntheses and PET images of high quality.…”

19-Fluorine nuclear magnetic resonance chemical shift variability in trifluoroacetyl species

“…13,14 As in the previous section, the variation of ring size and topology influences the shielding of 19 F NMR resonances for these compounds.…”

“…In this case, the observation of a resonance at δ = −72.04 ppm in the 19 F NMR indicates a single, cross-conjugated, dienol tautomer. 14 This deshielding trend is even more evident in compound 28, where we constrain the topology and electronic effects with the bicyclic, aromatic, naphthol system. 14 In this instance, the hydroxyl group cannot participate in tautomerization to a ketonic form since that would require loss of aromaticity.…”

“…14 This deshielding trend is even more evident in compound 28, where we constrain the topology and electronic effects with the bicyclic, aromatic, naphthol system. 14 In this instance, the hydroxyl group cannot participate in tautomerization to a ketonic form since that would require loss of aromaticity. The additional aromatic ring system in 28 further deshields the CF 3 group, resulting in a shift upfield of 0.4 ppm relative to 27.…”

“…Certain TFA groups attached to molecular residues that extend conjugation or permit tautomerization can, however, be deshielded by as much as 15 ppm. 8,9,[12][13][14] As the Figure 2 shows, α,α,α-trifluoro-β-diketone tautomerization from the diketo form (π Csp2-Osp2 ) to a keto-enol form (π Csp2-Csp2 ) results in a shift of the 19 F NMR resonance for the −CF 3 group to a lower field as a result of diminished shielding by the C=C enolic topology. To illustrate this trend, the 19 F NMR spectra of 1,3-ditrifluoroacetyl-2-indanone, 2-trifluoroacetyl-1-tetralone and 3-trifluoroacetyl-2-naphthol ( Figure 3) show how keto-enolic and ring-size substrate topology influences chemical shift.…”