Structure Dependence in Asymmetric Deprotonative Fluorination and Fluorocyclization Reactions of Allylamine Derivatives with Linked Binaphthyl Dicarboxylate Phase-Transfer Catalyst.

The asymmetric fluorofunctionalization of γ,γ-disubstituted allylamine derivatives (e.g., 3, 7, and 8) was investigated using our dianionic phase-transfer catalyst. Depending on the substituents on the alkene moiety, the reaction afforded chiral allylic fluorides and fluorinated dihydrooxazines in a highly enantioselective manner (up to 99% ee). The absolute stereochemistry of these products was found to be opposite to that in our previously reported fluorocyclization of γ-monosubstituted allylic amides (e.g., 13 and 14). To probe this interesting phenomenon, we investigated the influence of the substitution pattern of the alkene moiety on the reaction by means of NMR experiments and kinetic studies. The rate laws of the deprotonative fluorination and the fluorocyclization of γ,γ-disubstituted substrates were v = k[cat]0.6, while that of the fluorocyclization of γ-monosubstituted substrates was v = k[substrate][cat]0.4. An exponent of less than 1 suggests the involvement of an aggregated state of the catalyst ion pair in the catalytic cycle. Interestingly, a positive nonlinear effect was observed in the reactions of the γ,γ-disubstituted substrates, while a negative nonlinear effect was observed in the case of the γ-monosubstituted substrates. Thus, the reaction pathway depends on the presence or absence of an alkyl substituent at the γ position of the substrates, and on the basis of our mechanistic studies we propose that the active catalytic species for γ,γ-disubstituted substrates is a catalyst ion pair aggregate, whereas that for γ-monosubstituted substrates is the more active monomeric catalyst ion pair species, even though its concentration would be low.

Asymmetric Dearomative Fluorination of 2-Naphthols with a Dicarboxylate Phase-Transfer Catalyst.

A linked dicarboxylate phase-transfer catalyst enables smooth asymmetric dearomative fluorination of 2-naphthols with Selectfluor under mild conditions to give the corresponding 1-fluoronaphthalenone derivatives in a highly enantioselective manner. This reaction, which is compatible with a range of functional groups, is the first example of catalytic asymmetric fluorination of 2-naphthols, and is expected to be useful in the synthesis of bioactive molecules.

Enantioselective 5-exo-Fluorocyclization of Ene-Oximes.

The enantioselective 5-exo-fluorocyclization of ene-oxime compounds was demonstrated under phase-transfer catalysis. Although deprotonative fluorinations competed, the chemical yields and the ee values of the desired isoxazoline products were generally moderate to good. The absolute stereochemistry of the major isomer was determined to be S by comparison with the literature after transformation of the product to the corresponding iodinated isoxazoline.

Dianionic Phase-Transfer Catalyst for Asymmetric Fluoro-cyclization.

Inspired by the dicationic nature of the electrophilic fluorinating reagent, Selectfluor (1), we rationally designed a series of dicarboxylic acid precatalysts (2), which, when deprotonated, act as anionic phase-transfer catalysts for asymmetric fluorination of alkenes. Among them, 2a having the shortest linker moiety efficiently catalyzed unprecedented 6-endo-fluoro-cyclization of various allylic amides, affording fluorinated dihydrooxazine compounds with high enantioselectivity (up to 99% ee). In addition to cyclic substrates, acyclic trisubstituted alkenes underwent the reaction with good diastereoselectivity, whereas low diastereoselectivity was observed for linear disubstituted alkenes. Results suggest that the reaction proceeds via a fluoro-carbocation intermediate.

Asymmetric Fluorination of Cyclic Tetrasubstituted Alkenes with a Pendant Amide Groups under Dianionic Phase-Transfer Catalysis.

Asymmetric fluorination of cyclic tetrasubstituted alkenes with a pendant amide group was investigated under dianionic phase-transfer catalysis. Fluorination proceeded with high face selectivity, affording the corresponding allylic fluorides with a chiral tetrasubstituted carbon center with up to 97% enantiomeric excess (ee). It should be noted that deprotonative fluorination occurred mainly in preference to intramolecular nucleophilic attack of the amide group.

Asymmetric Dearomatizing Fluoroamidation of Indole Derivatives with Dianionic Phase-Transfer Catalyst.

Asymmetric dearomatizing fluorocyclization of indole derivatives was investigated using a dicarboxylate phase-transfer catalyst. This reaction proceeds under mild reaction conditions to provide fluoropyrroloindoline derivatives in a highly enantioselective manner. Various substitution patterns on the indole ring are well tolerated. To facilitate the reaction and ensure reproducibility, the addition of water is essential, and its possible role is discussed.