Nazarov cyclization fluorine

Ichikawa, J., Miyazaki, S., Fujiwara, M., Minami, T. Fluorine-Directed Nazarov Cyclizations A Controlled Synthesis of Cross-Conjugated 2-Cyclopenten-1-ones. J. Org. Chem. 1995, 60, 2320-2321. 

Fluorination in tandem of Nazarov cyclization succeeds in the case of alkenoylarenes. That both reactions are catalyzed by Cu(OTf)2 is most pleasing. 

Q -electron-donating effect of fluorine to control the regiochemistry (Scheme 3). Analogous to silicon, tin is also used to direct the Nazarov cyclization. " The interrupted Nazarov reaction has been developed by West et al. to extend the reaction of the cationic endocyclic intermediate with carbon nucleophiles. Furthermore, this reaction has been extended to imino-Nazarov cyclization of vinyl allenyl imine. ... 

Ichikawa and co-workers have examined the Nazarov cyclization of difluorodienone 107 (Scheme 19.28) and have shown that it leads selectively to cross-conjugated dienone product 110. The Nazarov cyclization was initiated by exposure of 107 to trimethylsilyl triflate in a mixed solvent of dichloromethane and hexafluoroisopropanol (HFIP), leading to the resonance tautomers 108 and 109 of the intermediate cyclic allylic cation. Tautomer 109 is disfavored because of the electrostatic effect of the two fluorines on the adjacent carbon atom therefore, the process is terminated through proton loss from the methyl group rather than from the n-butyl group. Elimination of one of the (3 fluorine atoms leads to 110 as the observed final product. 

SCHEME 19.29. Activation and control of the Nazarov cyclization by fluorine. 

Nie J, Zhu HW, Cui HF, Hua MQ, Ma JA. Catalytic stereoselective synthesis of highly substituted indanones via tandem Nazarov cyclization and electrophilic fluorination trapping. Org. Lett. 2007 9 3053-3056. 

An interesting catalytic diastereo- and enantioselective tandem transformation via Nazarov cyclization /electrophilic fluorination has been efficiently promoted by a (/ ,/ )-Ph-BOX-Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity trans/cis up to 49/1) and moderate-to-high enantioselectivities (up to 95.5% ee) (Scheme 44.24). This catalytic enantioselective tandem transformation can be used for synthesis of organofluorine compounds with adjacent carbon- and fluorine-substituted tertiary and quaternary stereocenters. " ... 

SCHEME 44.24. Ph-BOX-Cu(II)-catalyzed tandem Nazarov cyclization/electrophilic fluorination. 

A synthesis of cross-conjugated 2-cyclopenten-l-ones from dialkenyl ketones is readily induced by TMSOTf (eq 73). A strong fluorine-directing effect has been observed for such Nazarov-type cycUzation, as mixtures of products have been observed for nonfluorinated dialkenyl ketones. The addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a cosolvent dramatically accelerates the cyclization. Other acids such as BF3-OEt2, FeCls, polyphosphoric acid, or TiOH are less effective while neither TMSI nor TMSOMe promote this cyclization at all in CH2CI2. 3-Ethoxycarbonyltetrahydro-)/-pyrones also undergo such Nazarov-type cyclization. ... 

In the presence of (la) or Me3Si[B(OTf)4], the intramolecular Friedel-Crafts-type reaction of P,p-difluoro-a-enones with arenes proceeds smoothly to give 4-fluoro-1,2-dihydronaphthalenes in good yield [113]. The stabilizing effect of fluorine on a-carbenium ions enhances the reactivity to enable the rapid, efficient reaction at 0 °C (Scheme 9.44). The directing effect has also been utilized for a Nazarov-type cyclization [114]. 

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