gem-Difluoroolefin synthesis: general methods via thermostable difluorovinylmetals starting from 2,2,2-trifluoroethanol derivatives

Ichikawa, Junji

doi:10.1016/s0022-1139(99)00268-7

Cited by 105 publications

(57 citation statements)

References 69 publications

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“…19, 20 For example, the dehydrofluorination/metallation reactions of acetal 3a and carbamate 3b have been used to prepare stannanes 4a and 4b. We deployed 4a in a synthesis of pentulose analogues 21 and 4b in syntheses of difluorinated carbasugar analogues.…”

mentioning

confidence: 99%

One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

Kyne¹,

Percy²,

Pullin

et al. 2011

Org. Biomol. Chem.

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confidence: 99%

One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

Kyne¹,

Percy²,

Pullin

et al. 2011

Org. Biomol. Chem.

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“…Both reactions were conducted as a one-pot operation. 7 We attempted the regioselective protonation of 1,1-difluoroalk-1-enes 1 to generate a-fluorocarbocations, F NMR yield relative to internal PhCF 3 standard. b Np = Naphthyl.…”

Section: Methodsmentioning

confidence: 99%

“…ArX (0.9 equiv), CuI (1.0 equiv), Pd 2 (dba) 3 ·CHCl 3 (0.02 equiv), Ph 3 P (0.08 equiv), THF-HMPA (4:1), r.t., 1-15 h. which were expected to get trapped by the aryl moieties. Treatment of a model substrate 1e with trifluoromethanesulfonic acid or fluorosulfonic acid-antimony pentafluoride (1:1) (Magic Acid, FSO 3 H·SbF 5 ) in dichloromethane (Table 1, entries 1 and 2) led to a simple addition product, 2-benzyl-1,1-difluorohexyl trifluoromethanesulfonate (6) or 1-phenyl-2-trifluoromethylhexane (7). 8 Since the addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a cosolvent brought about a dramatic improvement in the fluorine-directed Nazarov cyclizations, 5 we adopted HFIP as a solvent in the attempted cyclization.…”

Section: Methodsmentioning

confidence: 99%

Friedel-Crafts Cyclization of 1,1-Difluoroalk-1-enes: Synthesis of Benzene-Fused Cyclic Ketones via α-Fluorocarbocations

Ichikawa¹,

Jyono²,

Kudo³

et al. 2004

Synthesis

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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

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“…Thus, we designed b,b-difluorostyrenes 5 and 6 bearing 2-iodoethyl and 2-cyanoethyl groups at the o-position as precursors of 2-fluoronaphthalenes. These substrates 5 and 6 were prepared as outlined in Scheme 1 via the one-pot sequence that we have previously established for a wide range of gem-difluoroalkenes [18]. 2,2-Difluorovinylboranes 2 were prepared in situ from 2,2,2-trifluoroethyl p-toluenesulfonate 1 and trialkylboranes.…”

Section: Synthesis Of 2-fluorinated Naphthalene Derivativesmentioning

confidence: 99%

Ring-fluorinated naphthalene and indene synthesis via 6- and 5-endo-trig cyclizations of gem-difluoroalkenes by carbon nucleophiles

Ichikawa

Miyazaki

Sakoda

et al. 2004

Journal of Fluorine Chemistry

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gem-Difluoroolefin synthesis: general methods via thermostable difluorovinylmetals starting from 2,2,2-trifluoroethanol derivatives

Cited by 105 publications

References 69 publications

One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

Friedel-Crafts Cyclization of 1,1-Difluoroalk-1-enes: Synthesis of Benzene-Fused Cyclic Ketones via α-Fluorocarbocations

Ring-fluorinated naphthalene and indene synthesis via 6- and 5-endo-trig cyclizations of gem-difluoroalkenes by carbon nucleophiles

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