2- methyl-1-indanone

None of the trifluoromethyl dibenzoheterocyclic salts synthesized above successfully trifluoromethylated enolate anions derived in situ from ketones with a base, with the exception of an enolate anion derived from 2-methyl-1-indanone, which has a tertiary a-carbon. The reactivity of the enolate anions may have been too great for these dibenzoheterocyclic salts. There-... 

The reaction of the lithium enolate of 2-methyl-1-indanone with the thiophenium salt (35) leading to the 2-trifluoromethyl derivative in 51% yield is an exception. With all other in situ generated enolates of ketones, no trifluoromethylation was observed. To moderate the reactivity of the enolates, a boron Lewis acid (40) was added to form the boron complexes. This made a regio-, diastereo- and enantio-selective trifluoromethylation possible in good to high yields. ... 

With 2-methyl-1-indanone, high ee s were obtained with some aryl bromides, but very low ee s with p-substituted aryl bromides, a result with no ready explanation. The postulated reaction pathway is shown below (Scheme 1), although it is unclear where the enantioselective-determining step occurs. 

Muzart and coworkers have succeeded in a catalytic asymmetric protonation of enol compounds generated by palladium-induced cleavage of 3-ketoesters or enol carbonates under nearly neutral conditions [47,48]. Among the various optically active amino alcohols tested, (-i-)-e do-2-hydroxy-endo-3-aminoborn-ane (25) was effective as a chiral catalyst for the enantioselective reaction. Treatment of the P-ketoester of 2-methyl-1-indanone 58 with a catalytic amount of the amino alcohol 25 (0.3 equiv) and 5% Pd on charcoal (0.025 equiv) under bubbling of hydrogen at 21 °C gave the (P)-enriched product 59 with 60% ee... 

Scheme 9) [48]. The enantioselectivity was highly dependent on the reaction temperature and almost enantiopure 2-methyl-1-indanone (59) was obtained at 52 °C. The reaction was assumed to proceed via an enol or palladium enolate intermediate which was produced by cleavage of the benzyl-oxygen bond and the subsequent decarboxylation. 

N HCl in ethyl acetate added with stirring at 0° to a soln. of 2-methyl-1-indanone in toluene, n-butyl nitrite in toluene then added slowly, stirred 1 hr. at 0° and an additional hr. at room temp. 2-hydroxy-3-methylisocarbostyril. Y 69%. F. e. s. E. J. Moriconi et al., J. Org. Ghem. 28, 2215 (1963). 

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. 

In an attempted explanation, the initial ketyl cyclizes to 2-methyl indanone, which is always detected in the initial stages of the stirred reaction, and the liberated amide base deprotonates the allylic methylene group. The resulting carban-ion cyclizes to a-naphthol. Thus, sonication probably accelerates the formation of the ketyl in such a manner that only cyclization to 2-methyl indanone occurs. If valid, this interpretation would confirm the rule according to which polar processes are not affected by sonication, in contrast to SET reactions. 

Treatment with triethylsilane and boron trifluoride etherate allows a variety of methyl (i-hydroxy-/3-ary lpropionates to be reduced to methyl ft -ary lpropionates in yields of 85-100% as part of a synthetic sequence leading to the preparation of indanones (Eq. 31).170 Small amounts of dehydration products formed simultaneously are reduced to the methyl -arylpropionates by mild catalytic hydrogenation.170... 

With lower hydrochloric acid concentration and reversal of the mode of addition, i.e., acid to indanone-nitrite mixture, the intermediate 2-methyl-2-nitroso-l-indanone may also be isolated as its dimer. This can be isomerized to the isocarbostyril rapidly in refluxing methanolic sodium methoxide and more slowly in concentrated hydrochloric acid.4... 

Ceric ammonium nitrate promoted oxidative addition of silyl enol ethers to 1,3-butadiene affords 1 1 mixtures of 4-(/J-oxoalkyl)-substituted 3-nitroxy-l-butene and l-nitroxy-2-butene27. Palladium(0)-catalyzed alkylation of the nitroxy isomeric mixture takes place through a common ij3 palladium complex which undergoes nucleophilic attack almost exclusively at the less substituted allylic carbon. Thus, oxidative addition of the silyl enol ether of 1-indanone to 1,3-butadiene followed by palladium-catalyzed substitution with sodium dimethyl malonate afforded 42% of a 19 1 mixture of methyl ( )-2-(methoxycarbonyl)-6-(l-oxo-2-indanyl)-4-hexenoate (5) and methyl 2-(methoxycarbonyl)-4-(l-oxo-2-indanyl)-3-vinylbutanoate (6), respectively (equation 12). 

Poor stereoselectivity (<30% ee) is recorded for the Michael addition of 1,3-di-ketones with nitroalkenes using cinchona bases [50] and early work recorded <25% ee using N-methylquininium and quinidinium hydroxides [51, 52], In contrast, indanones have been reported to react with methyl vinyl ketone in the presence of a cinchoninium salts to produce a chiral (S)-product in >95% yield (80% ee) [7]. Surprisingly, the (R)-isomer is obtained less readily (ee 40-60%) using cinchoni-dinium salts. Both isomers are obtained in high optical purity (>80% ee) via alkylation with 1,3-dichlorobut-2-ene and subsequent ring closure yields the Robinson... 

Catalytic asymmetric methylation of 6,7-dichloro-5-methoxy-2-phenyl-l-indanone with methyl chloride in 50% sodium hydroxide/toluene using M-(p-trifluoro-methylbenzyDcinchoninium bromide as chiral phase transfer catalyst produces (S)-(+)-6,7-dichloro-5-methoxy-2-methyl-2--phenyl-l-indanone in 94% ee and 95% yield. Under similar conditions, via an asymmetric modification of the Robinson annulation enqploying 1,3-dichloro-2-butene (Wichterle reagent) as a methyl vinyl ketone surrogate, 6,7 dichloro-5-methoxy 2-propyl-l-indanone is alkylated to (S)-(+)-6,7-dichloro-2-(3-chloro-2-butenyl)-2,3 dihydroxy-5-methoxy-2-propyl-l-inden-l-one in 92% ee and 99% yield. Kinetic and mechanistic studies provide evidence for an intermediate dimeric catalyst species and subsequent formation of a tight ion pair between catalyst and substrate. 

Figure 5. Variations of the chiral phase transfer methylation of indanone 5.

Table I. Effect of Catalyst/Indanone Ratio on Rate and Selectivity of the Chiral Methylation ...

These observations showed that the reaction can be simplified by preformation of the indanone enolate in toluene/50% NaOH and subsequent addition of catalyst and CH3CI (Figure 12). This eliminates the "induction period and most importantly the high sensitivity of rate and ee to the catalyst/indanone ratio. Detailed kinetic measurements on this preformed enolate methylation in toluene/50% NaOH determined that the reaction is 0.55 order in catalyst. This is consistent with our finding that the catalyst goes into solution as a dimer which must dissociate prior to com-plexation with the indanone anion. If the rate has a first order dependence on the monomer, the amount of monomer is very small, and the equilibration between dimer and monomer is fast, then the order in catalyst is expected to be 0.5. The 0.5 order in catalyst is not due to the preformation of solid sodium indanone enolate but is a peculiarity of this type of chiral catalyst. Vlhen Aliquat 336 is used as catalyst in this identical system the order in catalyst is 1. Finally, in the absence of a phase transfer catalyst less than 2% methylation was observed in 95 hours. 

Vlhen the chiral methylation is carried out with 30% aqueous NaOH the indanone is deprotonated at the interface but does not precipitate as the sodium enolate (Figure 11). In this system there are 3 to 4 molecules of H2O per molecule of catalyst available while in the 50% NaOH reactions the toluene is very dry with only 1 molecule of H2O available per catalyst molecule thus forcing the formation of tight ion pairs. Solvation of the ion pairs in the toluene/30% NaOH system should decrease the ee which we indeed observe with an optimum 78% versus 94% in the 50% NaOH reaction. In the 30% NaOH reactions the ee decreases from 78% to 55% as the catalyst concentration increases from 1 mM to 16 mM (80 mM 5, 560 mM CH3CI, 20 C). Based on these ee s rates of formation of (-h)-enantiomer and racemic product can be calculated. When the log of these rates are plotted versus the log of catalyst concentrations (Figure 13) we find an order of about 0.5 in the catalyst for the chiral process similar to that found using 50% NaOH consistent with a dimer-monomer pre-equilibrium. The order in catalyst for the... 

Experimental Procedure 2.2.6. Cyclopentannulation with a Molybdenum Aryl-carbene Complex 3-Hexyl-5-methyl-l-indanone 346]... 

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

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

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