Triquinacene synthesis

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). 

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]. 

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. 

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... 

One molecule that might be expected to be homoaromatic, if the phenomenon can exist in neutral species, is triquinacene (Fig. 9.7) the three double bonds are held rigidly in an orientation which appears favorable for continuous overlap with concomitant cyclic delocalization of six n electrons. Indeed, its potential aromaticity was one of the reasons cited for the synthesis of this compound [58], A measurement of the heat of hydrogenation of triquinacene found a value 18.8 kJ mol 1 lower than that for each of the next two steps (leading to hexahydrotriqui-nacene) [59]. This was taken as proof of homoaromaticity in the triene, i.e. that the compound was 18.8 kJ mol-1 (4.5 kcal mol 1) stabler than expected for an... 

The initial synthesis of triquinacene (356) and, in fact, the coinage of its trivial name are due to Woodward and co-workers (Scheme 55).337 The lengthy route began with isodrin (349) which was converted to alcohol 350 by a procedure devised by... 

A most expeditious synthesis of triquinacene was described by Deslongchamps and his co-workers in 1973 (Scheme 58).3S°) This approach comprised degradation of Thiele s acid (363) to diketone 364 and photolysis of this intermediate to give keto aldehyde 365. Aldolization of365 led to construction of the tricyclic nucleus sequential hydride reduction, mesylation, and elimination of this intermediate over alumina efficiently provided 356. 

The shortest synthesis of triquinacene is the four-step conversion from cyclo-pentadiene described by Wyvratt and Paquette (Scheme 59).351,352) Oxidative coupling of sodium cyclopentadienide with iodine generated 9,10-dihydrofulvalene (368)3S3,354) which was treated in situ with diethyl azodicarboxylate. The resulting... 

Serratosa has critically evaluated the various entries to the triquinacene system available via Pauson-Khand chemistry, concluding that a route involving cycloaddition of the dibenzylated enyne substrate (Schemes 17 and 23) is operationally the simplest for preparation of multigram quantities of tricy-clo[5.2.1.0 °]decane-2,5,8-trione. This in turn is a key intermediate for the study of synthetic entries to dodecahedrane and its derivatives. An optically active version of this synthesis has l n developed as... 

Triquinacene 10 which is now reasonably well accessible by a six to seven step synthesis [1,2], has long been envisaged as the logical precursor to acepentalene 3 [43] (see Scheme lb). Woodward et al. developed the first synthesis for triquinacene 10 [43] and suggested that it should be a potential precursor to both the fully unsaturated tricycle acepentalene 3 and dodecahedrane 88 [ 1,44]. Although many attempts have been made to cyclodimerize triquinacene 10,... 

The facile thermal [2 + 2 + 2] cycloreversion of diademane 51 (R=H, Scheme 12) is an interesting formation, but not a viable synthesis of triquinacene 10 [48,49]. This rearrangement in which three cyclopropyl cr-bonds of 51 open to form the three 7r-bonds of 10 is a concerted process and occurs at only 80 °C... 

Scheme 10.10 outlines Deslongchamps synthesis of triquinacene derivatives. Manipulation of Thiele s acid (146) gave the key product, 147. A photochemical fragmentation gave 148. and an intramolecular aldol... 

Pericydic Processes involving Non-concerted Steps.—Synthesis of triquinacenes have been discussed above. The hydrocarbon (388) [=(359)] is remarkably stable to heat. At 600 °C it gives azulene in low conversion with loss of 2H. At 700 °C the azu-lene secondarily isomerizes to naphthalene but t,2-dihydronaphthalene is also formed from triquinacene. At 750 °C some indene is formed with loss of CH2. The formation of azulene is unexpected. It is suggested that initial loss of 2H takes the molecule out of the set of (CH) o isomers and skeletal rearrangement via (389) to azulene is a possibility. At the higher temperatures isomerization via (390)—(393) would provide a path to the other products, each step being known or reasonable. The rates of the thermal conversions (394) (395), (395) - (396X and (394) - (396) at 200 °C are... 

With the disclosure of this protocol for the synthesis of 57, the opportunity to rapidly generate triquinacene analogs became viable. One of... 

Anionic homoaromatic compounds are quite few, such as the bis-diazene dianion in Fig. 4.3. However, whether or not neutral species can be homoaromatic is still a matter of debate. Some of neutral molecules used to be considered as homoaromatic, such as the fulleroid, 1,2-diboroetane and triquinacene in Fig. 4.3 but their homoaromaticity characters are either in question or denied. Thus, the establishment of experimental models for potential neutral homoaromatic molecules has long been an exciting pursuit in synthetic and theoretical chemistry. The central challenges remain the development of efficient synthesis, and the collection of detailed experimental data, in order to gain a deep insight into the structure-reactivity relationship. 

Cadieux JA, Buller DJ, Wilson PD (2003) Versatile route to centro-substituted triquinacene derivatives synthesis of 10-phenyltriquinacene. Org Lett 5 3983-3986... 

Triquinacene (50) is another hydrocarbon that has long been of interest. One reason is that an appropriate dimerization of triquinacene would provide dodecahedrane (51). From the standpoint of synthesis, triquinacene forces one to address the problem of five-membered ring synthesis. In addition, it is interesting to examine the difunctional relationships used in syntheses by practitioners in the field. 

I will start with the Woodward synthesis. Triquinacene is symmetrical and thus, it is not surprising that the synthesis (plan) passes through a series of symmetrical intermediates. For example, it was felt that triquinacene could be prepare by elimination of two moles of H-X from an intermediate such as 52 or 53. At this point it is difficult to know what provided Woodward with the insight that led back to 54 as a projected intermediate. Perhaps it was recognition that the known compound 56, derived from norbornadiene and cyclopentadiene, was only one carbon-carbon bond away from containing the triquinacene carbon skeleton as a substructure. 

The synthesis began with 56, which had been described by the Winstein group at UCLA. Oxidation to ketone 57, and epoxidation from the steri-cally most excessible face of the olefin, provided 55. Base mediated intramolecular opening of the epoxide established the final carbon-carbon bond of the triquinacene skeleton, as alluded to above. Oxidation of 58 to the diketone was accompanied by hydrate formation to provide 54. It was now necessary to break two carbon-carbon bonds to reveal the tricyclic nucleus of triquinacene. This was accomplished by treatment of 54 with lead tetraacetate to reveal anhydride 59, with the first of three double bonds present in triquinacene in place. 

---