2-Substituted 1-indenones

Carbonylation of halides in the presence of terminal and internal alkynes produces a variety of products. The substituted indenone 564 is formed by the reaction of o-diiodobenzene. alkyne, and CO in the presence of Zn[414]. 

Another interesting [3+2] cycloaddition in aqueous media was recently reported by Murakami.131 2-Cyanophenylboronic acid reacted as a three-carbon component with alkynes or alkenes to afford substituted indenones or indanones (Eq. 4.67). The use of an alkynoate even produced benzotropone, a formal [3 + 2 + 2] adduct. 

Evidence for the involvement of the diprotonated species 40 and 42 includes 13C NMR data, which shows deshielding of the involved carbons as the acidity of the media increases from H0 —8 to —26 (mesityl oxide is estimated to be fully monoprotonated in acids of about H0 —8). Dication 42 has been shown to be capable of reacting even with very weak nucleophiles, for example, abstracting hydride from cyclohexane.19b An analogous species (43) has been proposed in interaction with excess AICI3. Protonated cyclohex-2-enone is converted to 3-methylcyclo-pent-2-enone in HF-SbFs solution at 50°C.20 The reaction mechanism is thought to involve the dicationic intermediate 44 (eq 13). Likewise, aryl-substituted indenones are converted to the dications by reaction in superacid (eq 14).21... 

An interesting synthetic route to 2,3-substituted indenones 205 was discovered by the annulation of alkynes with o-iodobenzaldehyde (203) [86], In this reaction, the CH bond of the aldehyde may oxidatively add to Pd(0) to generate the hydridopalladium 204, which produces indenones 205 by reductive elimination. 

Using 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

The complex [Ir(cod)py(PCy3)]+ (41) as the PF6 salt has been found to be superior to complex (23) in the selective hydrogenation of steroids to the 5a product.165 Indenones and a series of substituted cyclohexenols could also be hydrogenated in good yield and with generally very high selectivity with (41).166 A brief summary of some of the above chemistry is available.167... 

Using Ni(CO)4 as both reducing agent and cycloaddition mediator, o-diiodobenzene may be induced to serve as a benzyne equivalent in a cycloaddition with alkynes leading to indenones. Yields are consistently good and regioselectivity with terminal alkynes for the 2-substituted product excellent (equation... 

The reversibility of the cycloaddition or cyclodimerization via radical cation could be observed in certain cases. For example [209], with some indenones (Scheme 38), cyclodimerization into truxones may occur but the radical cation of the cyclodimer may lead to other kinds of cyclodimer. Note also that the open radical cation is strongly sensitive to the presence of residual water. Other induced [4 + 2]-cycloaddition reactions implying 2-vinylpyrroles and y6-accept or substituted enamines were described [210]. 

Galatsis, P., Manwell, J. J., Blackwell, J. M. Indenone synthesis. Improved synthetic protocol and effect of substitution on the intramolecular Friedel-Crafts acylation. Can. J. Chem. 1994, 72, 1656-1659. 

Cascade intermolecular carbopalladations of alkynes followed by intramolecular trapping with electrophiles represent not only a novel type of organic transformation involving vinylpalladium intermediates, but also provide synthetically useful routes toward differently substituted indenols, indanones, indenones, and naphthy-lamines." Although these protocols are restricted to the intramolecular trapping with electrophiles, a wide application of this methodology toward the synthesis of various types of complex carbocychc compounds may be anticipated in the near future. 

In 1997 Murai s group developed a two-step procedure for the synthesis of 2-substituted inden-l-ones [56]. The reaction pathway comprised a carbonylation at a C-H bond and subsequent intramolecular aldolcondensation. Aromatic imines were applied as starting materials and coupled with both ethylene and trimethylvinylsilane to yield indenones in moderate to good yields (Scheme 6.18). 

Hydroxyl derivatives have been employed to synthesize indenones and quinolines (Table XI-20). The lactone XI-164, obtained from ester was converted to a variety of A -substituted lactams (XI-16S), which ere then reduced to the tetrahydronaphthyridines (XI-166) (Table XI-20). 

Two general approaches were used to synthesize 2-cyano-l-indenones with different alkyl groups at the 3-position. The first was an expansion of the Campaigne synthesis (Figure 1, Scheme A), which required the s mthesis of substituted ylidenemalononitriles, 2, and their sub uent cyclization in concentrated sulfuric acid. One limitation of this procedure in the expansion of the SAR was that for small R groups (i.e. lower alkyl), the cyclization did not occur. 

An intramolecular version of this tandem reaction has been applied to the synthesis of indanones and indenones (Scheme 4-294). Accordingly, a sequence of pentacarbonyliron-catalyzed isomerization, aldolization, and dehydration can be exploited to transform vinyl sugars into substituted cyclopentenones (Scheme 4—295). The latter represent versatile intermediates for the synthesis of a variety of natural products. ... 

West also demonstrated that oxyallyls derived from pyran-4-ones can participate in electrophilic aromatic substitution reactions. Irradiation of pyran-4-ones 34 with aryl groups appended in the 2-position produced tricyclic tetrahydrobenz[e]indenone 35 in fair to moderate yield (Table 81.4). Capture of the oxyallyl intermediate by solvent and Type A rearrangement to pyran-2-ones competed with the desired intramolecular EAS reaction. Interestingly, the yield of 35 was concentration dependent (higher yields with dilution). It is not clear how concentration affects the bifurcation of the oxyaUyl intermediate between intramolecular trapping and rearrangement. 

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