1,1-Difluoroalk-1-enes bearing a phenyl group at the C-3, -4, or -5 position, readily obtained from 2,2,2-trifluoroethyl p-toluenesulfonate, are treated with FSO 3 H·SbF 5 to undergo FriedelCrafts cyclization in (CF 3 ) 2 CHOH. The cyclization takes place via a-fluorocarbocations, followed by spontaneous hydrolysis of the C-F bond to afford bicyclic ketones including a five, six, or sevenmembered ring in good yield.Fluorine possesses a-carbocation stabilizing effect caused by donation of its unshared electron pair to the vacant porbital of the a-carbon, despite its leaving group ability as a fluoride ion (F -) due to its high electronegativity. 1 In contrast to a number of theoretical and mechanistic studies on fluorinated carbocations, 2 their synthetic applications are quite limited. 3 Furthermore, there are few reports on reactions utilizing both of the two properties mentioned above. 4 Recently, we have reported such an example, the fluorine-directed Nazarov cyclization of 2,2-difluorovinyl vinyl ketones, which proceeds via a-fluorocarbocations, generated by silylation of the carbonyl oxygen with TMSOTf, to afford b-fluorocyclopentenones with accompanying loss of a fluoride ion (Scheme 1). 5
Scheme 1The Nazarov cyclization of 2,2-difluorovinyl vinyl ketones Reagents and conditions: i. TMSOTf (1.0 equiv), CH 2 Cl 2 -HFIP (1:1), r.t., 10 min.Our interest in fluorine-containing carbocations prompted us to investigate: (i) the generation of a-fluorocarbocations from simple 1,1-difluoroalk-1-enes without a carbonyl group; and (ii) their reaction with an intramolecular aryl group instead of an alkenyl group. The a-cation-stabilizing effect was expected to direct the reaction of 1,1-difluoroalk-1-enes with a protic acid, so that protonation would preferably occur on the inner carbon of the olefinic part, leading to terminal carbocations rather than tertiary cations. Herein we report the Friedel-Crafts cyclization of 1,1-difluoroalk-1-enes bearing an aryl group 1, which provides a variety of fused bicyclic ketones 2. 6 Initially, the 1,1-difluoroalk-1-enes 1a-h bearing an aryl group at the C-3, -4, or -5 position were designed as the Friedel-Crafts substrates. We have already established a one-pot synthesis of 1,1-difluoroalk-1-enes from commercially available 2,2,2-trifluoroethyl p-toluenesulfonate (3) via boron-mediated alkylation followed by palladium-catalyzed coupling reaction with organohalides (Scheme 2). Monosubstituted difluoroalkenes 1a-d were readily prepared by protonolysis of in situ generated difluorovinylboranes 4 via the corresponding vinylcopper species 5 (Scheme 2, Eq. 1); disubstituted difluoroalkenes 1e-h were prepared by the cross-coupling reaction of vinylcoppers 5 with aryl or benzyl halides in good yield from 3 (Scheme 2, Eq. 2). Both reactions were conducted as a one-pot operation. 7