I-Indanone

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... 

This simple, one-step ring expansion is the only available method for the preparation of 2-hydroxy-3-alkylisocarbostyrils in good yield from the corresponding 2-alkyl-l-indanones. Table I lists five new hydroxyisocarbostyrils prepared in this manner. 

Prepare 6-methoxy-l-indanone (I) (JCS 1986(1962)) using polyphosphoric acid made by diluting 500 g of the commercial acid with 120 g 85% phosphoric acid. 2.5 g (I) in 176 ml ether and reflux one hour with 0.27 g lithium aluminum hydride. Cool and carefully add water and filter when bubbling stops (can use Celite filter aid). Dry and evaporate in vacuum and store twelve hours at -15° (under N2 if possible) to precipitate the white 6-methoxy-l-indanol (II) (recrystallize-n-hexane). 2.5 g (II) in 73 ml benzene and reflux one-half hour with 0.2 g p-toluenesulfonic acid. Cool, add water and separate the phases. Extract the aqueous phase with ether and combine with benzene phase and dry, evaporate in vacuum to get 5-methoxy-indene (III) (can distill 110-45/10). 1.53 g (III) and 1.39 g N.N-diethyl-aminoethyl-Cl.HCI in benzene (prepare the free base in benzene as described previously). Reflux four hours with 0.42 g sodamide, cool, wash with water and dry, evaporate in vacuum to get the indene analog of 6-methoxy DET as a dark liquid (can crystallize as oxalate). Alternatively, dissolve 2.51 g (III) in ether and treat (under N if possible) with 12 ml 1.6M buty-Li in hexane at 0-10°. After two hours cool to -30° and add 12 ml more of butyl-Li. Add ether suspension of 2.5 g N,N-diethylaminoethyl-CI. HCI over one-half hour and warm to room temperature. Filter, evaporate in vacuum to get the 6-methoxy-DET analog. 

D. L. Hughes, U.-H. Dolling, K M Ryan, R F. Schoene-waldt, E. I. J. Grabowski, A Kinetic and Mechanistic Study of the Enantioselective Phase-Transfer Methyla-tion of 6,7-Dichloro-5-methoxy-2-phenyl-l-indanone , J. Org. Chem. 1987, 52, 4745-4752... 

It has already been seen (see Section II,B and V,E) that vinylketene complexes of cobalt6,95 and chromium22 react with alkynes to produce cyclo-pentadienones, indanones, and substituted phenols. It has been shown108,109,144,145 that similar products may be derived from the alkyne adducts 247. Indeed, when alkyl or aryl substituted alkynes were reacted with vinylketene complex 221.e, a mixture of organic and organometallic products was isolated. In the cases where the alkyne is attached to an aromatic substituent, the expected alkyne adduct (247.h and 247.i) is isolated in low yield. However, when the vinylketene complex was treated... 

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

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... 

The Pd-catalyzed carbonylation of o-vinylaryl bromides using Mo(CO)6 as CO source with microwave irradiation gave indanone 338 and 3-acylaminoindanone 340, which are key intermediates for the synthesis of inhibitors of human immunodeficiency virus type 1 (HIV-1) protease and Plasmepsin I and II (Scheme 46). These polycyclic compounds were obtained in less than 30 min in high yields. The results clearly indicate the power and advantage of this protocol, especially for the combinatorial parallel synthesis of a library of compounds. 

The ultraviolet spectrum in the 300-350 m/i region showed that less than 1% of 1-indanone was present. If the 2-indanone darkens on standing, it can be repurified by steam distillation or by crystallization from ethanol. 

Keywords veratraldehyde, 4-phenylcyclohexanone, 1-indanone, aldol reaction, ,/i-unsaturated ketone... 

N. P, S COMPOUNDS Acetophenone Methyl acetophenone Phthalic Anhydride Methyl benzoate Indanone Dibenzofuran Diethyl phthal ate Di butylphthalate Di i sobutylphthalate Di (2-ethyl hexyl) phthal ate Diphenyl amine... 

Crystallization-induced asymmetric transformation has already been described by Leuchs in 1913 during the resolution of 2-(2-carboxybenzyl)-l-indanone with brucine.34 In this case spontaneous racemization occurred. More recently researchers at Sanofi observed spontaneous racemization during the resolution of 3-cyano-3-(3,4-dichlorophenyl)propionic acid (7), most likely as a result of the basic resolving agent [>-(-)-N-1 n etli y I g I near nine [d-(-)-MGA] (8) (Scheme 7.6).35 The enantiopure cyano acid, obtained in 91% overall yield, is subsequently reduced to (+)-4-amino-3-(3,4-dichlorophenyl)-l-butanol (9), a key intermediate in the phase 2 synthesis of tachykinin antagonists. 

The imine 20 from (R)-PGA 1 with 1-indanone 21 was obtained in 90% yield and ee >98% after boiling in i-PrOAc for 6 hours in the presence of a catalytic amount of p-TsOH H20 (Scheme 25.8). Prolonged heating under reflux of the mixture resulted in partial racemization of the chiral transfer agent. 

Many of the above-described examples highlight the diastereoselectivity of the solid-state reaction. Cyclic ketones with cis- or trans-a,a -substituents give the ring-contraction product with the same relative stereochemistry. Examples include 2-indanones 157 and 159 (Scheme 2.38), cyclohexanones 162 and 164—167 in Scheme 2.39, and ketones 177 and 179 in Scheme 2.43. The diastereospedfidty and enantiospecificity of linear ketones was also tested with the pentasubstituted acetone derivative 187 in its racemic and enantiomerically pure forms (Scheme 2.45). Notably, both samples reacted efficiently and in a completely diastereo-specific manner when reactions were carried out to 60% conversion. Sample of ( I )-(2R,4S)-187 gave the corresponding combination product in 100% ee and... 

Replacing the alkoxy carbene substituent by a better electron-donating amino group stabilizes the metal carbonyl bond. As a result, CO insertion in vinyl carbene D is hampered instead, cyclopentannulation via the chromacyclohexadiene I leads to aminoindenes K, which are readily hydrolyzed to indanones L (Scheme 6) [20]. 

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