Indenones, synthesis

The mechanism of the indenone synthesis (Scheme 3) seems to involve (1) oxidative addition of the aryl iodide to Pd(0) (2) arylpalladium coordination to the alkyne and subsequent insertion of the alkyne to form a vinylpalladium intermediate (8), (3) then either the vinylic palladium intermediate adds to the carbonyl group and subsequently undergoes a /3-hydride elimination (path A) or the alde-hydic C-H bond may oxidatively add to the palladium to produce an organopalla-dium(IV) intermediate (six-membered ring palladacycle) which subsequently undergoes rapid reductive elimination of the indenone and palladium (path B). The actual mode of ring closure of the vinylic palladium intermediate to the inde-... 

A catalytic but low-yield Rh-based indenone synthesis from benzene, alkynes and CO, involving a hydrogen migration is also known P. Hong, B.-R. Cho and H. Yamazaki, Chem. Lett., 1979, 339. 

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. 

Hsynthesis from, 3, 767 Indenobenzazepines pharmacological properties, 7, 546 Indenone oxide, 2,3-diphenyl-photochromic compound, 1, 385 In deno[ 1,2-c][ 1,2,4]triazines synthesis, 3, 434 Indicated hydrogen nomenclature, 1, 33 Indigo, I, 317, 318-319, 4, 370 Baeyer synthesis, 1, 319 colour and constitution, 1, 344-345 molecular structure, 4, 162 photochromic compound, 1, 386 synthesis, 4, 247 Indigoid dyes... 

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.). 

This type of 1,4-addition reaction has also been applied to optically active indenone derivatives in the synthesis of enantiomerically pure (C/D)-frmw-dihydro-l.f/-indenones, precursors for nortestosterone281 see also refs 282, 283 and 397. 

During the synthesis of an indenone derivative, Hoomaert found that AICI3 catalyzed the dimerization of indenone 34 to form truxone 35 (Scheme 2.3) [23]. Attempts to... 

Ishikawa and coworkers reported a synthesis of ( )-0-methylkinamycin C (54) [32, 33]. Their retrosynthetic analysis is shown in Scheme 3.9. It was envisioned that 54 could be derived from the dihydroindanone 55 by D-ring oxygenation, installation of the diazo substituent, and oxidation of the protected hydroquinone function. The dihydroindanone 55 was envisioned to arise from the enol ether 56, itself formed from an endo Diels-Alder reaction between the indenone 59 and the diene 58. 

In a total synthesis of coriandrin 68, the isocoumarin unit is generated by the thermal rearrangement of an indenone epoxide 67, the first application of a cycloreversion route to isocoumarin synthesis (Scheme 46) <00TL3677>. 

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]. 

Table 1. Examples of C-H transformations of aldehydes synthesis of indenones.

The central bond in (photochemically) easily accesible bicyclo[n.2.0]-alkan-2-ones (n = 3,4) can be cleaved by retro-aldol reaction (cf. Sch. 2), but also by treatment with Broenstedt- and Lewis-acids. This is shown in Sch. 16 for the synthesis of (i)descarboxyquadrone (55) starting from indenone 56 via the cycloadduct 57 which reacts with HC1 to 58 [69], or by the preparation of the AB-ring core of Taxol 59 from cyclopentenone 60 via cycloadduct 61 which rearranges to 62 in the presence of TiCl4 [70]. 

The microwave-assisted synthesis of indeno[l,2-h]pyridmes 12 and 13 have been reported by Tu and co-workers [63]. The 5//-mdeno[l,2-h]pyridin-5-one framework is present in the alkaloids from Annonaceae species that represent a small but biologically intriguing group of compounds [64, 65]. Applying a micro-wave-assisted MCR with a suitable aldehyde, an acetophenone, a 1,3-indanedione or a 1 -indenone and ammonium acetate in DMF, a small library of compounds 12... 

An intermolecular Pauson-Khand reaction of a dihydrofuran intermediate was used to prepare a benz[ indenone, allowing for the first synthesis of a zirconocene benz[/]indene complex <03OL3153>. A stereoselective intermolecular Pauson-Khand reaction of 3-(R)-methyldihydrofuran was used to construct the desired diastereoisomer of oxabicyclo[3.3.0]octanone ring shown below in the total synthesis of the sesterterpene terpestacin <03JA11514>. 

Padwa and co-workers (89TL2633 93JA2637) have elaborated an elegant modification of the cyclization/cycloaddition approach that involves the displacement of a carbene center and provides access to O-bridged compounds with an indenone moiety. An illustrative example is the synthesis of compound 718 through the Rh(II)-catalyzed decomposition of a-diazo ketones bearing tethered alkyne units in the presence of a dipolarophile (91JOC2523). 

During the enantioselective synthesis of (3aR,4R,7aS)-4-hydroxy-7a-methylperhydro-1-indenone, a suitable CD-ring fragment for vitamin D-anaiogs, M. Vandewalle et al. realized that the hydroboration/oxidation of (1,1)-ethylenedioxy-8a-methyl-1,2,3,4,6,7,8,8a-octahydronaphtalene led to a c/s-decalin structure instead of the literature reported trans-fusion." ... 

In recent years several closely related transition metal processes have been reported. For example, both catalytic amounts of Col2(dppe) [133, 134] and NiBr2(dppe) [135] in the presence of Zn metal and acetonitrile will effect this same indenol synthesis from o-haloaryl aldehydes or ketones and alkynes. Similarly, rhodium will catalyze the formation of indenones from simple aroyl chlorides and internal alkynes (Eq. 69) [136]. 

Recently, Larock and co-workers reported an efficient method for the synthesis of indenones 13 by the Pd-catalyzed annulation of o-iodobenzaldehyde 12 with internal... 

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. 

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