Regioselectivity in Intermolecular Pauson-Khand Reactions of Dissymmetric Fluorinated Alkynes

Abstract

Stoichiometric and catalytic intermolecular Pauson-Khand reactions (PKRs) of dissymmetric fluorinated alkynes were performed, affording regioselectively α-fluorinated cyclopentenones. Ethyl 4,4,4-trifluorobutynoate was an excellent substrate; its reaction with norbornadiene gave the corresponding PKR adduct in good yield and complete regioselectivity. Conjugate addition of nitroalkanes or cyanide to this adduct is stereospecific and entails concomitant loss of a trifluoromethyl group. This reaction can be exploited to prepare cyclopentenones featuring quaternary centers.

Synthesis and Application of β‐Substituted Pauson–Khand Adducts: Trifluoromethyl as a Removable Steering Group

“…These experiments are consistent with the observation that the loss of fluoride occurred after the Michael addition of nitromethane to the enone. Since a loss of fluoride in a-trifluoromethyl ketones had been reported by Mikami and Itoh, [15] and also took place in a related compound reported by our group, [11] we propose a plausible mechanism for this reaction (Scheme 5). After conjugate addition of nitromethane, elimination of fluoride would give a difluoroenone 5, which, after conjugate addition of water followed by a retro-aldol reaction would afford an intermediate enol 6.…”

“…[10] In previous studies of the intermolecular PKR of nonsymmetric fluorinated alkynes we observed that the electronwithdrawing effect of the fluorinated substituents had little impact on the regioselectivity. [11] Unexpectedly, these fragments ended up in the a-position of the PK adduct. To ascertain whether this was a purely steric effect, herein we studied the regioselectivity of the PKR of a family of trifluoromethylacetylenes.…”

Synthesis and Application of β‐Substituted Pauson–Khand Adducts: Trifluoromethyl as a Removable Steering Group

“…In previous studies of the intermolecular PKR of nonsymmetric fluorinated alkynes we observed that the electron‐withdrawing effect of the fluorinated substituents had little impact on the regioselectivity 11. Unexpectedly, these fragments ended up in the α‐position of the PK adduct.…”

Practical Methods for the Synthesis of Trifluoromethylated Alkynes: Oxidative Trifluoromethylation of Copper Acetylides and Alkynes

“…[3] Because of these unique properties of the trifluoromethyl group, tremendous efforts have been devoted recently to the development of new processes that allow for the introduction of a CF 3 subunit -mostly to an aromatic ring -with surgical precision and remarkable efficiency. [1d,5] In addition, they were shown to be excellent precursors for the synthesis of various trifluorinated building blocks such as arenes, [6] alkenes, [7] allenes, [8] enones, [9] enol esters, [10] methyl ketones, [7g,8a] Pauson-Khand adducts [11] or heterocycles. Trifluoromethylated alkynes clearly fall into this category and have recently found various applications in medicinal chemistry.…”