Tris-annelation

Dibenzo[/>,/]thiepin derivative (39) has been obtained by cyclization of 2-arylthio-5-nitrophenylpyruvic acid (38) in the presence of polyphosphoric acid 33>. The use of this Friedel-Crafts type reaction is restricted to the synthesis of the stable di- and tri-annelated thiepins such as 40 33), 41 7), and 42 34). 

Table 16. Structural Data of Tris-Annelated Benzenes...

Optically active estrone. Danishefsky and Cain have reported a synthesis of optically active estrone that utihzes the tris-annelating pyridine reagent (1). 

T riphenylphosphine—Diethyl azodi-carboxylate, 280, 645 Triphenylphosphine dibiomide, 645-646 Triphenylphosphine dichloride, 646-647 Triphenylphosphine dihaiides, 647-648 Triphenylphosphine diiodide, 648 Triphenylphosphine ditriflate, 648 Triphenylphosphite methiodide, 649 Triphenyl phosphite ozonide, 435 Triphenyl(prop-2-ynyl)phosphonium bromide, 494 Triphenylsilanol, 655, 656 Triphenylstannane, 649 Triphenyltin hydride, 649 Triphenylvinylsilane, 637 Triphosphopyridine nucleotide, 36-37 Tri- -propyl orthovanadate, 655 Tris-annelation, 410 Ttis(aquo)hexa-fi-acetato-p,-oxotri-ruthenium acetate, 425-426,650 Tris(dimethoxyboryl)methane, 328, 329 Tris(dimethylamino)borane, 554 Trishomocubanone, 108 Tris(neomenthyldiphenylphosphine)-chlororhodium, 416... 

The first synthesis of a tri-annelated system occurred 30 years after its initial discovery from coal-tar in 1832 by Dumas and Laurent when Limpricht hydrolyzed benzyl chloride under heat to afford anthracene [laj. The most significant improvement on anthracene production, however, came in 1868 when Liebermann and Graebe obtained it via Zn-dust distillation of the natural product alizarin [la]. An interesting dimer, known as dianthracene or p-anthracene 11, was obtained by several groups in the 1890s by irradiation of anthracene solutions (Scheme 1.3) [9]. Irradiation of several anthracene derivatives afforded similarly novel structures... 

We know of three species containing the bismethylenecyclopropane substructure for which enthalpies of formation are available the annelated benzocyclopropene and naphtho[h]cyclopro-pene, and the tris-methylene species, [3]-radialene [see J. F. Liebman and A. Greenberg, Chem. Rev., 89, 1225 (1989)]. However, none of these data seems particularly useful in the current context. 

The pKR+ value for the parent tri(l-azulenyl)methyl cation (2a+) is 11.3. Hydrocarbon-based carbocations, which comprise only of carbon and hydrogen, are generally very reactive species. Some extremely stable hydrocarbon carbocations, which exist even under basic conditions, were reported in the literature (5). However, most of these examples are cyclic cations, such as cyclopropenylium or tropylium ions (Figure 8). The tropylium ion 8+ annelated to three bicyclo[2.2.2]octane units is one of the most stable hydrocarbon-based carbocation ever reported (9). 

Notably, stabilization of the cation-radical center prevents a proton from being expelled. The cation-radical of tris(bicyclopentyl)annelated benzene is not prone to proton loss, entirely, owing to the spin-charge location more or less in the aromatic (nodal) phase (Rathore et al. 1998b Scheme 1.21). 

A twofold intramolecular Heck reaction of the dibromobenzene derivative 19 has been used to construct the heptacyclic skeleton 20 of cephalostatin analogs. This reaction required a precise control of the reaction time and temperature. The conversion proceeded best with a catalytic amount of the palladacycle from tris(< -tolyl)phosphine and palladium acetate, and gave exclusively (in 80% yield) the heptacycle 20 with an unusual m-annelation of the two newly formed rings (Scheme 10). ... 

In dimethylsulfoxide, the two starting cation radicals of Scheme 1-35 have pKa values of -20 and -25, respectively (Bordwell Cheng 1989). It is clear that both species give rise to the stabilized carboradicals after deprotonation. Electron-donating substituents increase the stability of the arene cation radical and render the odd-electron species less acidic for example, the cation radical of hexamethylbenzene has a pKa value of only 2 in AN (Ama-tore Kochi 1991). The cation radical of tris(bicyclopentyl)annelated benzene is not prone to proton loss, due entirely to the spin-charge location more or less in the aromatic (nodal) phase (Rathore Lindeman et al. 1998), Scheme 1-36. 

Electrophilic Substitution Reactivity Much of the electrophilic reactivity of aromatics is described in great detail in a comprehensive recent book of Taylor [10]. We shall focus attention on the electrophilic substitution reactivity of annelated benzenes and try to interpret the orientational ability of fused small rings. For this purpose we consider here Wheland transition states of the electrophilic substitution reactions. It is also convenient to take the proton as a model of the electrophilic reagent. In order to delineate rehybridization and 7r-electron localization effects, let us consider a series of angularly deformed benzenes (Fig. 21), where two vicinal CH bonds bent toward each other mimick a fused small ring. Angles c of 110° and 94° simulate five and four membered... 

The reaction of allenylsilanes with electron deficient ir-systems constitutes a powerful and general method for the tegio- and stereo-selective preparation of substituted cyclopentenes. As first reported, (trimethylsilyl)allenes function as three-carbon nucleophiles in TiCU-promoted (trimethylsilyl)cyclopen-tene annelations (Scheme 31). The annelation process involves the polarization of an a,p-unsaturated carbonyl compound by TUTU to generate an alkoxyallylic cation. Regiospecific electnqrhilic substitution of this cation at C-3 of the allenylsilane produces a silicon-stablizied vinyl cation. A 1,2-shift of the tri-... 

This is a vast improvement over the old procedure using butadiene, dichlorodimethyl-silane, and ordinary magnesium powder in hexamethylphosphoric triamide and requiring several days at elevated temperatures.34 The reaction must be carried out in an autoclave and gives a single annelation product. No mention was made in this paper if Kl-activated magnesium had been tried. 

In the course of the studies on transannular interaction [76] between heteroatoms, Furukawa and co-workers have recently reported some interesting new stable azasulfuranes [77], sulfurane dications bearing two sulfur atoms [78], and selenurane dications bearing two sulfur and selenium atoms as ligands which are annelated in two five-membered diazocine skeletons. As shown in Scheme 35, the central sulfur atom of the tris-sulfide 76 can be converted... 

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