Triquinane ring system

In a representative example of this type, complexed l-ethoxy-2-ethynylcyclopropane 7 was used in the Pauson-Khand reaction with cyclopentene to give the cyclopropyl-substituted bi-cyclo[3.3.0]octenone 8, which on thermal rearrangement of the vinylcyclopropane unit gave the triquinane ring system 9 ... 

In the synthesis of ( )-pentalenene, the PKR was used to construct the angularly fused triquinane ring system 77 from cyclopentene 76. 

The aforementioned examples of ewdo-annulated bicyclo[2.2.2]octenones led to photoproducts containing a linear c/s a ti ds-triquinane framework. The stereochemical feature of the photoproducts in these examples is a direct consequence of stereoselectivity in the ODPM reaction and the orientation of the annulated ring. It is interesting to note that the sensitized irradiation of compound 198 with an exo-annulated five-membered ring gave the tetracychc compound 199 containing a folded cis syn cis-triquinane ring system (Scheme 37). ... 

It should be noted that this strategy could also be utilized to build up the linear triquinane framework 3-257 in 45% yield, employing the 11-membered ring system 3-256 in which the BMDMS group is simply moved from one to the other side of alkyne moiety as compared to 3-252 (Scheme 3.66) [105],... 

Briggs et al. proposed a new strategy for the synthesis of tricyclic structures using acyl xanthates as precursor for acyl radicals [121]. Irradiation with visible light of a solution of acyl xanthate in presence of 1,6-diene 126 afforded czs-fused bicyclic compound 127 in a good yield (Scheme 38). Radical reduction of xanthate and subsequent aldol condensation leads to the formation of [5.5.5]-fused ring systems similar to those of the triquinane terpene family. 

Synthetic applications of [2 + 2] photocycloadditions of unactivated alkenes have been limited due to the low regioselectivity and stereoselectivity observed in this process. However, Wender recently reported an intramolecular example of a diene- iene photochemical [2 + 2] which provides rapid access to cif-fused 5-8 ring systems and subsequently linearly fused triquinanes. ° Sensitized irradiation of (65)... 

Intramolecular radical cyclizations are exceptionally useful and have found widespread use in organic synthesis [11,12]. Kolbe chemistry has been exploited in this manner providing access to the prostaglandin precursor 8 [13], and to ring systems (10) that are common to the angularly fused triquinane natural products [14]. 

Transannulation of the mesylate (33), derived from 4,8-dimethylcycloocta-4-en-l-ol, using sodium carbonate in aqueous dioxane has provided the bicyclo[3.3.0]octanol (34), a central precursor to the monoterpene iridomyrmecin (35 equation 13). In studies of the biomimetic synthesis of the natural tri-quinanes capnellene (37 equation 14) and pentalenene (40 equation IS) Pattenden et al. have shown that both molecules can be produced from appropriate cycloocta-l,S-diene precursors, i.e. (36) and (39) [or indeed their corresponding positional isomers (38) and (41), respectively] by treatment with boron trifluoride. Mehta et al. have described an alternative transannulation approach to the triquinane unit found in pentalenene, i.e. (42) - (43 equation 16), and also to the ring system (44 equation 17) found... 

Triquinanes rank among the most important natural carbon frameworks [12, 19], Angular- and linear-fused carbon skeletons possess three five-membered rings which share one or two carbon-carbon bonds, respectively. Natural products from a wide array of biological sources produce these compounds with a considerable range of functionality. A new radical anion tandem process to prepare two triquinane skeletons, linear and angular, was initiated by the radical anion of strained ring systems... 

Conformationally constrained triazacyclopenta[c]penta-lenes 128 are unprecedented tricyclic scaffolds and share the structural complexity characteristic of alkaloid natural products, such as triquinanes ° (e.g., 129 and 130), in that both scaffolds are composed entirely of fused five-membered rings and contain quaternary carbon centers (Figure 16.12). The triaza tricyclic ring system represents a source of chemical diversity that may complement traditional classes of heterocyclic compounds as potential pharmaceutical agents. 

Magnus was the first to develop extensive synthetic applications of the Pauson-Khand preparation of the bicyclo[3.3.0]oct-l-en-3-one system. His efforts amply demonstrate the degree to which the high level of functionality in the Pauson-Khand products can be directly utilized in building more complex structures. A formal synthesis of the antitumor sesquiterpene coriolin illustrates a very efficient sequence for construction of the third ring in the linearly fused triquinane series in the presence of considerable functionality (Schemes 10 and 18). A synthesis of the related triquinane hirsutic acid utilizes the observation that the proper stereochemical relationship between the substituents at C-7 and the ring-fusion carbon (C-5) of the bicyclo[3.3.0]oct-l-en-3-one system, while not controllable in the cycloaddition reaction itself, may be readily established by acid- or base-catalyzed equilibration (equation 54 and Scheme 19). ... 

In the laboratory of K. Fukumoto, the stereoselective total synthesis of (+)-A -capnellene was carried out using an intramolecular Diels-Alder reaction to obtain a tricyclic 5-5-6 system. Since the target molecule was a triquinane, the six-membered ring had to be converted to a five-membered one, a transformation achieved by a Wolff rearrangement. The required a-diazo ketone was prepared via a deformylative diazo transfer reaction and was photolyzed in methanol. The ring-contracted methyl ester was isolated as a 3 1 mixture of separable isomers favoring the a-isomer. 

This bicyclo[3.3.0]octenone preparation has been employed in numerous natural product syntheses. Scheme 5-4 shows an early adaption of one of the cycloadditions shown in Eq. (53) toward the synthesis of the linearly fused triquinane system in coriolin. The substitutional and stereochemical characteristics built in by the Pauson-Khand process lend themselves to a very efficient approach [120]. Angularly fused triquinanes have also been prepared by closing the third ring onto a bicyclic Pauson-Khand product [121]. 

Whereas the preceding processes involving ring openings of cyclopropanes provide useful [3+2] entries to cyclopentanes, the use of simpler substrates in [3+2] cycloadditions is made possible by the development of reductive cycloaddition pathways. Such reactions were initially developed in the context of stoichiometric processes, where metallacycles were prepared by oxidative cyclizations of enones and alkynes, followed by either protonation or alkylation of the nickel 0-enolate functionality. Catalytic protocols involving various intramolecular combinations of 7t-systems include formal [3+2] reductive cycloadditions of bis-enones to form bicyclooctanols (Scheme 3-33), of enones with unsaturated acyl oxazolidinones to form triquinane derivatives, and of enals with alkynes to form bicyclooctenols. ... 

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