Triquinanes linearly fused

Hirsutene (1) and A9(,2,-capnellcnc (2), the parent members of the hirsutane and capnellane families of triquinane natural products, respectively, are isomeric molecules that possess four contiguous stereogenic centers, one of which is quaternary. The linearly fused tricyclopentanoid frameworks of compounds 1 and 2 are obviously very similar, differing only with respect to the positions of the three methyl groups. An asset of Curran s tandem radical cyclization strategy is that it provides a unified entry into a wide variety of linear condensed cyclopentanoid natural products. As a result, it is possible to devise nearly identical retrosynthetic pathways for these structurally related molecules. 

The synthesis of other angularly fused triquinanes as well as linearly fused sesquiterpenes such as hirsutene and capnellene quickly followed. Many general methods for the synthesis of cyclopentanoid natural products emerged as a result of the target-oriented effort [6]. These accomplishments have been reviewed extensively on numerous occasions [7]. This chapter reviews the history of retigeranic acid from its isolation and structure determination to published approaches to its synthesis and the four total syntheses accomplished to date. 

More recently. Little has synthesized 667 during his studies of the applicability of 1,3-diyl trapping reactions to the construction of tricyclopentanoids Capitalizing on a reversal of the normal regioselective mode of these transformations which gives rise to linearly fused triquinanes, he decomposed diazene 670 in refluxing acetonitrile and immediately subjected the product mixture to a hydroboration-... 

Sternbach s work has offered a highly efficient synthesis of the linearly fused triquinane (+)-hirsutene 26, where intramolecular Diels-Alder reaction of the substituted cyclopenta-... 

Triquinanes, A new route to linearly fused triquinanes uses an intramolecular cycloaddition of a nitrone to a double bond (1 2). The product is a precursor to the... 

The potential of sequential radical addition as a powerful method to achieve the formation of five-membered rings was fully realized in the tandem radical cyclization strategy devised by Curran for the synthesis of triquinanes. In the case of linearly fused triquinanes, such as hirsutene 90 (Scheme 3.40), this strategy implies the retrosynthetic disconnection of the tricyclic framework by the application of two sequential radical cyclization transforms at rings A and... 

Asymmetric hydroboration using IpC2BH was also applied in the stereocontrolled synthesis of a linearly fused triquinane, (+)-hirsutic acid (eq 1) ... 

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)... 

Another major tricyclopentanoid structural motif, the tricyclo[6.3.0.(P ]undecane skeleton of the so-called linearly fused triquinanes, is also readily accessed by using the meta cycloaddition process, as... 

In a novel combination of Pauson-Khand cycloaddition with vinylcyclopropane chemistry, de Meijere has described an entry to linearly fused triquinanes beginning with cyclopropylalkynes. Cyclopentenone formation has been carried out with a variety of substitution patterns on the cyclopropane, and moderate yields achieved with both norbomene and cyclopentene as substrates. Thermal vinylcyclopropane-cy-clopentene rearrangement of the cycloaddition products leads to the final tricyclic system (Scheme... 

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). ... 

The linear triquinane skeleton is easily accessible from methyl 8-oxotricyclo-[5.4.0.0] undecan-l-carboxylate 67 [64]. Photoreduction of 67 affords ring-expanded intermediate 67" which cyclizes to the linearly fused triquinane 68 (Scheme 29, eq 1). An extension of this reaction to the heterocyclic angular tricyclic compound 70 has also been achieved starting from keto lactone 69 (Scheme 29, eq 2) [75]. 

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... 

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]. 

The skeieton of linear triquinane is easily accessible from the methyl 8-oxotricyclo I 5.4.0.0l undecan-l-carboxylate 150." Photoreduction of 150 implied the formation of a ring-expanded intermediate K which cyclized to produce the linearly fused triquinane 151 (Scheme 58). An extension of this reaction to heterocyclic angular tricyclic compounds has also been achieved (Scheme 59). This photofragmentation method has been ex-... 

Photochemistry, in the shape of the de Mayo reaction, also features in a new synthesis of the linear fused triquinane hirsutene (20). Thus, photocycloaddition between dimedone and 2-methyl-cyclopent-2-enol was accompanied by spontaneous retro-aldolization of the intermediate adduct (17), leading to (l8a). McMurry coupling of the dione (l8b), derived from (l8a), followed by manipulation of the functional groups in (19) then led to (+)-hirsutene... 

Reaction of linear compounds containing a ketone and diene functional groups with TMSC(Li)N2 produces alkylidene carbenes that undergo intramolecular cyclopropanation followed by formation of trimethylenemethane diyls and then [3 + 2]cyclo-addition, giving linearly fused triquinanes (eq 31). ... 

SCHEME 25.68. O-Stannyl ketyl approach to linear-fused triquinanes. 

Hwang, J.-T. and Liao, C.-C., Synthesis of angularly and linearly fused triquinanes via the common intramolecular Diels-Alder adduct of a masked o-benzoquinone. Tetrahedron Lett., 32,6583,1991. 

Singh, V. and Thomas, B., Aromatics to triquinanes synthesis and photoreaction of tricy-clo[5.2.2.0 > ] undecanes having an a-methoxy-P,y-unsaturated carbonyl chromophore a novel ef cient and general route to linearly fused cisiantixis tricyclopentanoids, /. Org. Chem., 62,5310, 1997. 

Recently reported rearrangements of linear triquinanes (244) to their angularly fused isomers (247) have been envisaged to involve the formation and equilibration of the enolates (245) and (246) followed by an intramolecular Michael addition of the enolate ion in (246) to the cyclopentenone moiety see Scheme 62. It has been reported that treatment of l,10-dibromobicyclo[8.1.0]undecane-3,8-dione (248) with triethylamine in dichloromethane results in the formation of a novel cyclopenta[(>]pyran derivative (249). The mechanism outlined in Scheme 63 has been postulated to account for this unusual transformation. 

Scheme 640 Synthesis of cyclopropane-fused linear triquinane.

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