1-Indanone, carboxylation

A total synthesis of dihydrolycorine (85), y-lycorane (87) and 8-lyco-rane (92), has been achieved starting from the indanone carboxylic acid 77. This, in turn, was obtained, like the tetralone ester 76, from the known anhydride (75) via Friedel-Crafts cyclization of the monomethyl esters obtained from 75 by treatment with 1 mole of methanol. Reduction of the methyl ester of 77 (LiAlH4), followed by Mn02 oxidation,... 

Here, the catalyst was ammonium compound 27, and 1 served as F-source. Under optimized conditions, methyl indanone carboxylate 26 was fluorinated with up to 68% ee. 

When dealing with polyalkylaromatic hydrocarbons, rearrangement of the substituents has been known to occur. Heilbrunn and Marechal have shown that when durene is reacted with MA in the presence of AICI3, a 75% yield of the indanone carboxylic acid 135 is obtained. Thus, both acylation as well as alkylation by the anhydride and olefin fragments of MA occur. 

The carboxylation of ketones is carried out essentially as in the preceding experiment, but at slightly higher temperatures (requiring an oil bath or mantle). Thus, acetophenone (6 g, 0.05 mole) in 100 ml of approx. 2 M MMC is stirred and heated at 110-120° for 1 hour. After cooling, hydrolysis in the acid-ice mixture, and isolation from ether, benzoylacetic acid, mp 99-100°, is obtained in 68% yield. Similarly, 1-indanone gives l-indanone-2-carboxylic acid, mp 100-101°, in 91 % yield. 

Protonated amides and carboxylic acids have also been shown to activate adjacent electrophilic centers. Although protonated carboxylic acids and amides are not typically considered stable cationic groups, in superacidic media they can be readily generated and many have been observed by spectroscopic studies.16 As an example of electrophilic activation by a protonated carboxylic acid, P-phenylcinnamic acid (35) is diprotonated in super- acid to give the dication (36, observable by NMR) which then reacts with benzene and gives the indanone (37) in good yield (eq 12).17 It is known that the 1,1-diphenylethyl... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

Chemical/Physical. Ozonation in water at 60 °C produced 7-formyl-1-indanone, 1-indanone, 7-hydroxy-l-indanone, l-indanone-7-carboxylic acid, indane-l,7-dicarboxylic acid, and indane-1-formyl-7-carboxylic acid (Chen et al, 1979). Wet oxidation of acenaphthene at 320 °C yielded formic and acetic acids (Randall and Knopp, 1980). The measured rate constant for the gas-phase reaction of acenaphthene with OH radicals is 8.0 x 10 " cmVmolecule-sec (Reisen and Arey, 2002). 

Indane 1 formyl 7 carboxylic acid, see Acenaphthene 1-Indanone, see Acenaphthene, Fluorene... 

Indanone, see Fluorene l-Indanone-7-carboxylic acid, see Acenaphthene Indene, see Di-n-butyl phthalate lodoformaldehyde, see Methyl iodide... 

Indanone was first prepared by distillation of the calcium salt of o-phenylenediacetic acid2 3 and, more recently, by the action of acetic anhydride on its potassium salt.4 It has been obtained by the dilute sulfuric acid-catalyzed hydrolysis and decarboxylation of 2-iminoindan-l-carboxylate6 and ethyl 2-indanone-l-carboxylate.6 2-Indanone is commonly obtained by acid-catalyzed dehydration of an indene glycol,7 8 as illustrated in this preparation. Indene glycol has been obtained from indene via the bromohydrin.9-12 The most recent preparation of 2-indanont is by Curtius degradation of 2-indenecarboxylic acid.13... 

Polymer catalysts containing cinchona alkaloids were re-examined by d Angelo for the reaction of l-indanone-2-carboxylate and methyl vinyl ketone, in which the structure of the spacer connecting the base moiety to the Merri-field resin dramatically influenced the enantioselectivity (Scheme 5) [12]. Catalyst 4 (n=7) with a 7-atom-length spacer to quinine exhibits 87% ee, while 4 (n=3) with a 5-atom spacer and 4 ( =9) with an 11-atom spacer gave only 13% and 31% ee, respectively. 

Scheme 1. Catalysis ofthe reaction of indanone 2-carboxylate with methyl vinyl ketone to afford Michael adduct 2...

Migration of the carbonyl during epoxide cleavage is used to produce hydroxy lactones from epoxides of carboxylic acids (Eq. 44) [84]. a-Acyl-2-indanones [85], furans [86], and A -oxazolines [87] (Eq. 45) can also be synthesized by cleavage and rearrangement of epoxides with BF3 Et20. 

For the synthesis of (69), the enol ether (71) from the indanone (70) was carboxylated with COa-n-butyl-Iithium in THF at —70 C to yield (72). The methyl ester (73) was converted into (75) via the maleic anhydride adduct (74), essentially as described in earlier work. Lithium aluminium hydride reduction followed by oxidation with dicyclohexylcarbodi-imide afforded the aldehyde (76). This was condensed with excess (77) to yield a mixture of the diastereomers (78). Oxidation with chromium trioxide-pyridine in methylene dichloride gave (79), which could be converted into the diketone (80) by treatment with excess benzenesulphonylazide. The diketo-lactam (81) was prepared from (80) as described for the synthesis of the analogous intermediate used in the synthesis of napelline. Reduction of (81) with lithium tri-t butoxyaluminohydride gave the desired dihydroxy-lactam (82). Methylation of (82) with methyl iodide-sodium hydride gave (83). Reduction of this lactam to the amine (84) with lithium aluminium hydride, followed by oxidation with potassium permanganate in acetic acid, gave (69). 

Indanone-3-Carboxylate/Cyanohydrin Route to Benzazepine 6 (Route B)... 

The first of these alternative approaches started with commercially available indanone-3-carboxylic acid 23 (derived from phenylsuccinic anhydride via Friedel-Crafts chemistry). This indanone was a viable precursor to 6 through an aminomethyl homologation with cyanide or nitromethane (Scheme 3.10). Our intent was to obtain ester 25, which after reduction would afford methylamine 28, which in turn would cyclize to generate lactam 29, giving benzazepine 6 upon reduction. Stereocontrol in the homologation was unnecessary, as lactam 29 would theoretically provide a thermodynamic sink under epimerizing reaction conditions, capturing the desired di-indane isomer. 

The cyclization of 3-phenylpropanoyl acid chloride to 1-indanone can be performed in boiling benzene with 90% yield. The in situ formation of mixed carboxylic-fluorosulfonic anhydride intermediates is suggested to account for the high catalytic activity of Nafion. 

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