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Volumn 65, Issue 33, 2009, Pages 6682-6695

Scandium triflate-catalyzed intramolecular Friedel-Crafts acylation with Meldrum's acids: insight into the mechanism

Author keywords

[No Author keywords available]

Indexed keywords

DIOXANE DERIVATIVE; LEWIS ACID; MELDRUM ACID; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; SCANDIUM; SCANDIUM TRIFLATE; TRIFLUOROMETHANESULFONIC ACID; UNCLASSIFIED DRUG;

EID: 67650217931     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2009.05.058     Document Type: Article
Times cited : (36)

References (122)
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    • Meldrum's acid derivatives are potent electrophiles when disubstituted at the 5-position (quaternized Meldrum's acids) and react with organolithium reagents in an inter- and intramolecular fashion, see:
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    • A limited number of intramolecular electrophilic aromatic substitution reactions of arenes with 5-alkylidene Meldrum's acid derivatives promoted by protic acids have also been described, see:
    • A limited number of intramolecular electrophilic aromatic substitution reactions of arenes with 5-alkylidene Meldrum's acid derivatives promoted by protic acids have also been described, see:
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    • Protic acid-promoted intramolecular Friedel-Crafts acylation with acyl Meldrum's acid derivatives were reported. Mechanistic evidences suggested a protonated acyl Meldrum's acid as the acylating agent, instead of a ketene or protonated ketene species, see:
    • Protic acid-promoted intramolecular Friedel-Crafts acylation with acyl Meldrum's acid derivatives were reported. Mechanistic evidences suggested a protonated acyl Meldrum's acid as the acylating agent, instead of a ketene or protonated ketene species, see:
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    • Formation of 2-(3-oxoacyl)pyrroles through Friedel-Crafts acylation of pyrrole with acylated Meldrum's acids, see:
    • Formation of 2-(3-oxoacyl)pyrroles through Friedel-Crafts acylation of pyrrole with acylated Meldrum's acids, see:
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    • Meldrum stated that the treatment of 2,2-dimethyl-1,3-dioxin-4,6-dione with excess of alkali 'was found to cause disruption into acetone and malonic acid'. However, no experimental data was provided, see:
    • Meldrum stated that the treatment of 2,2-dimethyl-1,3-dioxin-4,6-dione with excess of alkali 'was found to cause disruption into acetone and malonic acid'. However, no experimental data was provided, see:. Meldrum A.N. J. Chem. Soc. 93 (1908) 598-601
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    • The competitive reaction of an equimolar mixture of t-BuOH and EtOH with Meldrum's acid at reflux furnished a 1:3.8 ratio of the corresponding esters, see:
    • The competitive reaction of an equimolar mixture of t-BuOH and EtOH with Meldrum's acid at reflux furnished a 1:3.8 ratio of the corresponding esters, see:
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    • The competitive reaction of an equimolar mixture of t-BuOH and n-pentanol with acetylketene revealed a 8.2:1 selectivity favoring the less sterically demanding 1° alcohol, see
    • The competitive reaction of an equimolar mixture of t-BuOH and n-pentanol with acetylketene revealed a 8.2:1 selectivity favoring the less sterically demanding 1° alcohol, see:
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    • For ab initio studies on the formation of ketenes via pyrolysis of Meldrum's acid derivatives, see:
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    • Intramolecular arylation of ketenium ions, see:
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    • 2, see:
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    • note
    • The plot of the log(data) versus time was linear.
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    • Related studies of the thermal decomposition of 2,2,6-trimethyl-4H-1,3-dioxin-4-one have been reported with both kinetics experiments, see:
    • Related studies of the thermal decomposition of 2,2,6-trimethyl-4H-1,3-dioxin-4-one have been reported with both kinetics experiments, see:
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    • This compound decomposes to acetylketene and reacts just as described for acyl ketenes. These dioxinones do not require the initial enolization step, but still involve a retro hetero-Diels-Alder and acylation step. The rate-determining step in these reactions was determined to be a reversible, unimolecular loss of acetone to provide the reactive intermediate. It was also concluded that since the decomposition of 2,2,6-trimethyl-4H-1,3-dioxin-4-one is reversible, acetone is a competitor with other trapping reagents
    • Birney D.M., and Wagenseller P.E. J. Am. Chem. Soc. 116 (1994) 6262-6270 This compound decomposes to acetylketene and reacts just as described for acyl ketenes. These dioxinones do not require the initial enolization step, but still involve a retro hetero-Diels-Alder and acylation step. The rate-determining step in these reactions was determined to be a reversible, unimolecular loss of acetone to provide the reactive intermediate. It was also concluded that since the decomposition of 2,2,6-trimethyl-4H-1,3-dioxin-4-one is reversible, acetone is a competitor with other trapping reagents
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    • note
    • Similar inhibition by the 1-indanone product was postulated but not experimentally demonstrated.
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    • note
    • The stability of acyl ketenes, generated through retro hetero-Diels-Alder of Meldrum's acids, is enhanced by increasing the size of the substituent at the 5-position, see Ref. 18.
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    • 3-catalyzed Friedel-Crafts acylation with acid chlorides and anhydrides, see:
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    • note
    • At fixed time intervals, aliquots were drawn from the reaction mixture and immediately quenched in a triethylamine/methylene chloride solution. These samples were then filtered through plugs of silica, and then injected into a GC equipped with a flame ionization detector. The progression of the reaction was judged by the simple percent conversion as determined by the direct comparison of integration areas of the starting material with the product. Since no internal standard was used in the analysis, percent yields were not determined. All other reaction and analysis conditions were identical between each Lewis acid.
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    • note
    • For a large-scale synthesis, the removal of the acetone by-product by reduced pressure could be expected to accelerate the reaction, but this was not explored in this study.
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    • note
    • 2 has been shown to be effective catalysts for the Friedel-Crafts acylation of 42, see Ref. 4a.
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    • For examples of Friedel-Crafts acylation catalyzed by lanthanide bis(trifluoromethanesulfonate)amides, see
    • For examples of Friedel-Crafts acylation catalyzed by lanthanide bis(trifluoromethanesulfonate)amides, see:
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    • 2NH, see:
    • 2NH, see:
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    • 2O, see:
    • 2O, see:
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    • See also
    • See also:
  • 112
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    • 3 and MeOH, see:
    • 3 and MeOH, see:
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    • 13C NMR, see:
    • 13C NMR, see:
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    • note
    • 3 despite the extreme measures taken to dry the catalyst.
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    • 3-catalyzed aldol reactions with formaldehyde in water, the formation of TfOH was negligible and found not to be an active catalytic species, see:
    • 3-catalyzed aldol reactions with formaldehyde in water, the formation of TfOH was negligible and found not to be an active catalytic species, see:. Kobayashi S., and Hachiya I. J. Org. Chem. 59 (1994) 3590-3596
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