2-Indanones, formation

Indanone formation from the amino acid derivative shown in trifluoroacetic acid solution with 1 mole of trifluoroacetic anhydride occurred in 95% yield after refluxing for 3 hours (ref.82). 

Representative reactions that are thought to proceed through a CMD pathway and that use KOAc as the optimum base include the benzolactone formation via direct arylation of a tethered carboxylic acid (eq 33), indanone formation via direct arylation of cyclopropanol-derived homoenolates (eq 34), and the direct arylation of thiophenes with aryl bromides (eq 35). ... 

A possible mechanism was outlined by the authors. Coordination of diphenylacetylene to the cobalt complex could induce an electronic attack of the central cobalt metal on the aromatic ring and migration of the aromatic hydrogen to the acetylenic carbon initialing the C-H metalation step. Insertion of CO into the cobaltocycle complex gives the indenone. The resultant indenone could be hydrogenated by the [Co]-H species formed under water gas shift reaction conditions to furnish the indanone formation as discussed previously. 

Treatment of the acetylenic ketones 186 with lithium dialkylcuprates and trapping the resultant enolates with acetic anhydride produced the enyne-allene 187 (Scheme 20.39) [72], Regeneration of the oxyanion-substituted enyne-allene system using methyllithium at -20 °C led to the formation of either the indanones 188 or the ben-zofluorenones 189 through a Schmittel cyclization reaction. 

Generally phenol formation is the major reaction path however, relatively minor modifications to the structure of the carbene complex, the alkyne, or the reaction conditions can dramatically alter the outcome of the reaction [7]. Depending on reaction conditions and starting reactants roughly a dozen different products have been so far isolated, in addition to phenol derivatives [7-12], In particular, there is an important difference between the products of alkyne insertion into amino or alkoxycarbene complexes. The electron richer aminocarbene complexes give indanones 8 as the major product due to failure to incorporate a carbon monoxide ligand from the metal, while the latter tend to favor phenol products 7 (see Figure 2). 

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. 

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... 

Lee and coworkers ", studying the Beckmann rearrangement of 1-indanone oxime derivatives 240, observed that the pure E and Z oximes isomerize under mild acidic conditions such as silica gel (equation 72). In the presence of Brpnsted or Lewis acids as silica gel or AICI3 the high rotational barrier of C=N double bond would be lowered by the formation of a complex between the tosylate and AICI3 241. This fact makes the... 

Stabilized ketene 6S. For l, 2 -disubstituted epoxide, species 6S undergoes 6-endo-dig electrocyclization (path b) [24] to form the six-membered ketone 66, ultimately giving naphthol products. l, 2, 2 -Trisubstituted epoxide species 6S undergoes 5-endo-dig cyclization (path a) to give the ketone species 67, finally producing l-alkylidene-2-indanones. The dialkyl substituent of the epoxide enhances the 5-endo-dig cyclization of species 65 via formation of a stable tertiary carbocation 67. We observed similar behavior for the cyclization of (o-styryl)ethynylbenzenes [15, 16]. Formation of 2,4-cyclohexadien-l-one is explicable according to 6-endo-dig cyclization of a ruthenium-stabilized ketene, vhich ultimately afforded the observed products [25]. 

Thiopyrans have, in general, been less thoroughly investigated. The isothiochroman-4-one (245) on irradiation in basic methanol is converted to the indanone (246)199 a pathway involving electrocyclic ring opening and the formation of the intermediate (247) may be implicated. An alternative... 

Oxidative carbonylation of alkynyltungsten(II) complexes in excess triflic acid leads to formation of indanone derivatives424 [Eq. (5.161)]. Elucidation of the reaction mechanism was made by isolation and characterization of acyltungsten(IV) species indicating the involvement of the 17 -vinyl idene cation 115. 

Various attempts to hydrolyse 9-ethylenedioxybicyclo[3.3.1]nonane-3,7-dione under acid conditions resulted only in the formation of either 5-hydroxyindan-2-one (HCl/AcOH 14% yield) or a mixture of the indanone (13%) and 7,9-bis(ethylenedioxy)bicyclo[3.3.1]nonan-3-one (13% 10% aqueous HC1). 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

Using the enthalpy of formation of 1-indanone from [29], we find this reaction is exothermic by 8.1 kJ mol 1. We are not surprised that this reaction is less exothermic than the earlier one (1) because we have lost the conjugation energy associated with conjugation of a carbonyl group attached to a benzene ring. 

This reaction (13) is exothermic by 14 kJ mol-1 and so 2-benzoxazolinone seems to be nonaromatic. The same reaction enthalpy value as for 2-indanone (six n electrons), not far from indane (21 kJ mol-1), suggests that it lacks aromaticity other than found in its benzene ring, much as found for indane and the indanones. Admittedly, the enthalpy of formation of CH3NHCOOCH3(A,0-dimethylcar-bamate) is unknown however, we may estimate the value to be -420 kJ mol1 by assuming thermoneutrality for reaction 14 ... 

The oxime nitrogen lone pair of electrons must be properly oriented so as to interact with the rhodium carbenoid.84 Thus, subjection of the -oximino isomer 182 to a catalytic quantity of Rh2(OAc)4 in CH2C12 (40 °C) with a slight excess of DMAD afforded the bimolecular cycloadduct 184 in 93% yield. In sharp contrast, when the isomeric Z-oximino diazo derivative 183 was exposed to the same reaction conditions, only indanone-oxime 185 (80%) was obtained. The formation of this product is most likely the result of an intramolecular C-H insertion reaction. 

The photostimulated reactions with the enolate anions of 1-indanone and a-tetra-lone lead to the reduction product benzamide (23% and 44%, respectively), together with the target fused isoquinolinones (51% and 42%, respectively) [65]. The formation of benzamide can probably be ascribed to the hydrogen atom abstraction from the cyclic ketone. 

In the original discovery route by Sugimoto,19,46 aldol condensation of 5,6-dimethoxy-l-indanone (25) and l-benzyl-4-piperidine-carboxaldehyde (26) in the presence of freshly prepared LDA and hexamethylphosphoramide (HMPA) in THF provided exocyclic enone 27 in 62% yield (Scheme 2). Hydrogenation with 10% Pd/C followed by salt formation with hydrochloric acid afforded donepezil hydrochloride (3) in 86% yield. 

For the synthesis of tris-annulated benzene rings, the aldol trimerization of cyclic ketones has been known as a powerful tool since the 19 century. Why the reaction works so well with some ketones (e.g., indanone) but fails so miserably with others (e.g., tetralone), however, has never been adequately explained. This chapter outlines the development and scrutiny of a hypothesis that says formation of an a,/ -unsaturated (conjugated) dimer from a cyclic ketone is vital to the success of an aldol trimerization reaction for the synthesis of a tris-annulated benzene the reaction will fail with ketones that form only / ,y-unsaturated (unconjugated) dimers. This hypothesis unifies much experimental chemistry and is supported by theoretical calculations. 

The presence of ammonia may depress the formation of a secondary amine, and quite high yields of primary amines have often been obtained with ketoximes over Raney Ni in the presence of ammonia, as seen in the hydrogenation of l-(4-ethoxy-3-methoxyphenyl)-2-propanone oxime (eq. 8.15)24 and 3,3-dimethyl-l-indanone oxime,25 where the corresponding primary amine was obtained in 95 and 92% yields, respectively. 

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