Triquinacene

Acyl azides may loose N2 on heating and rearrange to isocyanates (Curtius rearrangement), which may be solvolyzed. Some of the possibilities of classical carboxyl conversions are exemplified in the schemes below, which are taken from a triquinacene synthesis (R. Russo, 1971 C. Merder, 1973) and the ergotamine synthesis of A. Hofmann (1963). 

All this is in line with the most recent finding for triquinacene, for which the direct determination of its AHy(g) from its experimentally measured heat of combustion finally corroborated the results of the most advanced computational studies that triquinacene is not homoaromatic [35]. Evidently, heat of combustion measurements should also be carried out for some representative [nlpericyclines to finally settle the quest for their neutral homoaromaticity. 

FIGURE 8. Structures of triquinacene (1) and hexaquinacene (2) (distances in A, angles in degrees)... 

Recently, Mascal and Ceron Bertran <2005JA1352> reported the preparation and characterization of 35 (aza-analogue anions of triquinacenes) which are stable enough in THF solution (in the absence of acid). Moreover, the hexachloro anion 35b could be isolated as tetraethylammonium salt by column chromatography on alumina. As expected, anion 35a was more nucleophilic than 35b. Indeed, only the former could be benzylated leading to 36a. However, 35b reacts easily with molecular bromine at low temperature yielding the corresponding a,a,a-tribromide 37b or dibrominated ether 37 b when this bromination was conducted in THF. 

Woodward et al. (1964) were the first to prepare triquinacene. They reported that there was no evidence in support of delocalization of the 1t system. Many subsequent studies reached the same conclusion (see Bunzli et... 

Photoelectron and electron transmission spectroscopy indicate that there is appreciable interaction between the acetylene units of [129] (Houk et al., 1985). Both homoconjugation and hyperconjugation are proposed. Dewar and Holloway (1984) suggest that the through-bond interactions dominate. Similar thermochemical studies to those performed with the triquinacene series were carried out on [129] and some acyclic homoconjugated acetylenes (Scott et al., 1988). From these data it was concluded that decamethyl[5]pericyclyne should be classed as a homoaromatic molecule. As already discussed for the triquinacene series, the species used as non-homoaromatic models (and the calculated compensations for strain energies) may be inappropriate and thus this conclusion should be treated with some caution. Using our probes for homoaromaticity we were not able to obtain any evidence in support of the homoaromaticity of [129] (Williams and Kurtz, unpublished results). 

Another approach to evaluating homoaromaticity is to compute various reaction properties such as heats of reaction. A typical example of this approach is a recent paper by Storer and Houk (1992) using molecular mechanics calculations (MM2) of the heats of hydrogenation of triquinacene [118]. In this study they conclude that the anomalous heat of hydrogenation can be explained without invoking homoaromaticity. The use of this type of computational data suffers the same problems as experimentally measured values there is an ambiguity with regard to separation of structural and electronic effects and how to choose appropriate reference systems. 

It is obvious that the isobutene unit provides a good starting point for the generation of trimethylenemethane radical anions. However, even isobutane units can be used to produce these more highly unsaturated species. In a preliminary work aimed at two-and three-fold deprotonation processes in solution, Kuck, de Meijere and coworkers165 have subjected triquinacene (41) and the tribenzotriquinacenes 44 to NCI conditions with... 

CH4/O2 and CF4 as the reactant gases and observed the formation of [M — 4 H] ions in the Cl plasma (Scheme 13)166. Thus, repeated deprotonation and electron transfer processes appear to offer an efficient access to more highly unsaturated and/or ring condensed trimethylenemethane radical anions. The [M — 4 H]- ion is considered identical to the molecular radical anion (42) of acepentalene (43), which was generated as a short-lived species from the former by neutralization-reionization mass spectrometry167. Efforts to apply Squires methodology to triquinacene 41 and the tribenzotriquinacenes 44 have been made168. 

Some illustrative examples from the field of polyquinanes are the synthesis of some derivatives of bicyclo[3.3.0]octane 6 (Scheme 6.7) [12] [15] -which have been used in the total syntheses of coriolin, hirsutic acid and quadrone- and the synthesis of triquinacene 7 and some of its derivatives. The retrosynthetic analysis of perhydrotriquinacene-l,4,7-trione (7a) is shown in Scheme 6.7bis. In the actual synthesis the hydroxy groups must be protected either as trialkylsilyl ethers or more conveniently as benzyl ethers [16] [17]. 

Khand annulations (extremely efficient in the synthesis of polyquinanes and cyclopentanoid sesquiterpenes -triquinacene, coriolin, etc.-, among many others). 

Strategies based on known, highly elaborated, but nevertheless readily accesible, starting materials with a "complexity index" as near as possible to the "complexity index" of the target molecule. This strategy has also been applied to non-natural compounds as, for instance, in the synthesis of triquinacene by Woodward [37] and in the syntheses of dodecahedrane by Paquette (Domino Diels-Alder adduct) [38] and Prinzbach ("pagodane") and their associates [39]. 

Full details have now appeared concerning the photoisomerization of triquinacene its bridgehead substitution via photochlorination and the S l solvolytic reactivity of these halides The three deuterated, optically active 2,3-dihydrotri-quinacenes 463 of known absolute configuration have been prepared from +)-462 (Scheme XXXVII) The dextrorotatory monodeuterated triquinacene 464 was... 

An alternative practical synthesis of triquinacene-2-carboxylic acid (as the dextrorotatory enantiomer) has l n described by Deslongchamps and Soucy Their protocol begins with hydroxy ketone 467 and passes via the 2-methyl derivative (Scheme XXXVIII). Selenium dioxide oxidation of the hydrocarbon provided the aldehyde which was further oxidized and then hydrolyzed to arrive at the add. 

Following resolution with (—)-quinine, (+)-465 was transformed into the (-l->2-formamido derivative which was condensed with the acid chloride of (+)-465 to give the secondary amide 468. From this point, the cyclic imidate salt 469 was prepared, but cyclization to the dodecahedrane nucleus could not be realired With Thiele s add as starting material, several routes to triquinacene and 2,3-dihydrotriquinacen-2-one 462) have been developed Triquinacene reacts with Mo(CO)g to give tricarbonyl(triquinacene)molybdenum (470) and with (CHjCI -... 

W(CO)3 to give tricarbonyl(triquinacene)tungsten X-ray analysis has revealed 470 to possess the indicated structure. 

Following the preparation of 2,6-di(bromomethyl)triquinacene 471), dimercaptan 472 was synthesize conventionally. Coupling of these intermeiates produced a 3.5 to 1 mixture of anti- and syn-triquinacenophanes 473 and 474. These [somers were separate chromatographically and identities established by x-ray structure determination of 473... 

Direct irradiation of the (CH)10 hydrocarbon triquinacene (26) in pentane solution gave five different (CH)10 isomers along with some naphthaline and azulene. The two major products were pentacyclo[4.4.0.02 4.03 i0.05,9]dec-7-ene (27), arising from an intramolecular [2 + 2] cycloaddition, and hexacyclo[4.4.0.02,4.03,10.05,8.07 9]decane ( barettane , 28), which is formed via a di-n-methane rearrangement (see Section l.A.2.2.) followed by an intramolecular [2 + 2] cycloaddition,50... 

An example of the inherent complexities in assigning homoaromaticity in neutral hydrocarbons, even when accompanied by thermochemical, molecular mechanical and/or quantum chemical analysis, is shown by the competing studies of the energetics of triquinacene ... 

Several systems have been examined in the context of potential tris- and higher homoaromatic systems21. These include cis. cis, cis-1,4,7-cyclonon atriene (128), triquinacene (129), hexaquinacene and the cyclic polyacetylenes such as 130. The conformations of some of these systems are such that they could be considered to be examples of in plane homoaromatic systems266. 

Oxidative cleavage of the organic fragment from the metal is possible using Ce and gives the tricyclic rearrangement product (34) in very high yields (equation 15) 45,46 The tetranitrile, (34), prepared in this manner has been used as a key intermediate in the synthesis of chiral 2-substituted triquinacene derivatives.51... 

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