Stereoelectronic structure of α-bromoalkenyl trifluoromethyl ketones

Abstract

The results of quantum-chemical calculations at the B3LYP/6-311G** level of theory showed that (Z)-α-bromo-β-arylalkenyl trifluoromethyl ketones are more stable than the corresponding E isomers by 4-5 kcal/mol. Relatively large positive charge on the olefinic β-carbon atom and strong polarization of the C=C bond in both Z-s-cis and Z-s-trans conformers makes bromoalkenyl trifluoromethyl ketones the most potent Michael acceptors among α,β-unsaturated carbonyl compounds. The calculated data are very consistent with the experimental IR spectra. Ar = Ph (a), 4-MeOC 6 H 4 (b), 2,5-(MeO) 2 C 6 H 3 (c), 2-thienyl (d).Unsaturated carbonyl compounds play an important role in synthetic organic chemistry and attract interest as model structures for theoretical studies. α-Halo derivatives of α,β-unsaturated carbonyl compounds exhibit a high reactivity toward nucleophilic reagents and are convenient models for studying transmission of electronic effects through the C=C(Hlg)C=O conjugated system [1,2]. It is known that introduction of a fluorine atom or fluorine-containing group into organic molecules considerably changes their physical and chemical properties. It is not accidental that the chemistry of unsaturated trifluoromethyl ketones has developed extensively during the past decades, and these compounds have been widely used in the synthesis of acyclic and carbo-and heterocyclic compounds [3][4][5][6]. Polyfunctionality and accessibility of haloalkenyl trifluoromethyl ketones makes them undoubtedly advantageous as intermediate products for the preparation of various biologically active substances and analogs of natural compounds. For example, we recently reported on unexpected one-pot transformation of 4-aryl-3-bromo-1,1,1-trifluoromethylbut-3-en-2-ones into indenols by the action of secondary amines [7,8].With a view to understand specific reactivity of alkenyl trifluoromethyl ketones having a halogen atom in the α-position, it is necessary to thoroughly analyze their structure and the nature of electronic interactions in their molecules. In the present work we examined the stereoelectronic structure of α-haloalkenyl trifluoromethyl ketones in comparison with their nonfluorinated analogs on the basis of the results of DFT quantum-chemical calculations (B3LYP/6-311G**) and IR spectral data.α-Bromo enones IIIa-IIId were synthesized according to a classical procedure implying bromination of initial enones Ia-Id and subsequent dehydrobromination of dibromo derivatives IIa-IId thus obtained [7, 8] (Scheme 1). α-Haloalkenyl trifluoromethyl ketones are typical captodative alkenes, which can exist as several stereoisomers A-D arising from cis-trans isomerism about the C=C bond and rotation of the trifluoroacetyl group about the C-C bond. According to the 1 H and 13 C NMR data, α-bromo enones O IIIa-IIId Br Ar CF 3 O Ia-Id Br 2 , CHCl 3 , 10°C Ar CF 3 O IIa-IId Br Br Scheme 1.

The Wonderful Chemistry of Trifluoromethyl α‐Haloalkenyl Ketones

“…The IR spectra of enones 1a – h each contain two strong absorption bands representing the C=O and C=C moieties. Their approximately equal intensities indicate the s‐cis conformation …”

Regioselectivity Issues in the Addition of Grignard Reagents to Trifluoromethylated α‐Bromoenones

“…The predominant formation of the 1,4‐adducts from fluorinated substrates can be attributed to the influence of the strong electron‐withdrawing CF 3 group which contributes to reinforce the Michael acceptor character of the enone. In fact, trifluoromethylated α‐bromoenones 1 differ from their non‐fluorinated analogs α‐haloenones and enals as they have a sufficiently large positive charge on the olefinic β‐carbon and a higher carbon‐carbon double bond polarization , . As a result, among α,β‐unsaturated carbonyl compounds, trifluoromethylated α‐bromoenones are the most reactive Michael acceptors.…”

Basicity of the polydentate captodative aminoenones. Ab initio , DFT, and FTIR study

“…For this reason, different aspects of the chemistry of both captodative and push–pull aminoalkenes bearing trifluoroacetyl substituent as a strong EWG attract special attention during the last decade . In continuation of our recent research in this field, we have performed a comparative examination of basic properties of captodative and push–pull fluorine‐bearing aminoalkenes and their non‐fluorinated analogues (Table ).…”