Of triquinanes

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 triquinane acids, initiated by the preparation of isocomenic acid [22], thus provided a general method for control of the stereochemistry of secondary methyl groups in these terpenes. The [4+1] annulation based on the dienes of type 23 then laid the groundwork for the first-generation design and a model study for the approach to retigeranic acid [23]. 

Scheme 10.10 Paquette s synthesis of triquinane portion of retigeranic acid...

Scheme 10.14 Wender s synthesis of triquinane part of retigeranic acid by meta-photocycloadditon...

Iterative trapping of the alkylpalladium species with tethered olefins is also possible, which allows tandem cycloisomerizations and zipper reactions to take place. Thus, depending upon the juxtaposition of the unsaturated bonds, Trost achieved highly atom-economical syntheses of triquinanes, propellanes (264) from the ynediene 263, and polyspiranes (Scheme 67).261... 

VIII Synthesis of Triquinane Natural Products O O O 1.N0BH4... 

Lange, G.L., Decicco, C.P., Willson, J., and Strickland, L.A. (1989) Ring expansions of [2 + 2] photoadducts. Potential applications in the synthesis of triquinane and taxane skeletons. Journal of Organic Chemistry, 54, 1805—1810. 

An elegant application of this photocycloaddition in the field of triquinane synthesis has been reported by Reddy and Rawal [160]. The initially formed oxetane 163, formed from the Diels-Alder adduct 162, is easily cleaved reductively (by use of LiDBB = lithium di-/er -butyl-biphenylide) to give 164. This approach was also used for the construction of structurally diverse di- and (propellane-type as well as linear or angular anellated) triquinanes [161]. The classic linear triquinane hirsutene is also available via this route [162]. Star-like molecules like the tiene 167 are available via a sequence of intramolecular photocycloaddition (from the 1,3-cyclohexadiene/acylallene adduct 165) and oxetane (166) ring-opening (Sch. 58) [163]. Further examples of intramolecular... 

Some double-bond shifts and isomerizations have been observed previous to the PKR. Sometimes 1,6 enynes have reacted partially as 1,7 enynes, or 1,8-enynes have isomerized to 1,7-enynes prior to the PKR [59,60,133]. In some intermolecular examples strained alkenes have isomerized totally before the cyclization giving unexpected products. An example, in the synthesis of triquinanes like 120, depicted in Scheme 33, the starting alkene 118 was isomerized to 119 prior to the reaction with 117 [134,135]. 

Scheme 33 A pre-PK double bond shift. Synthesis of triquinanes...

Scheme 54 Cycloaddition of diynes with dienes in the synthesis of triquinanes. Tandem [2 + 2 + l]/[4 + 2] cycloadditions...

Scheme 3 Round-trip strategy for the construction of triquinanes...

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... 

More sophistication was required to elaborate the pathway applicable for the synthesis of triquinane 165, a known precursor for the preparation of hypnofilin 166. The presence of a hydroxyl group in ring A of 166 dictated the use of a modified substrate for the tandem radical cyclization and an entirely different method for its triggering. A one-electron reduction of the aldehyde carbonyl in 167 by Sml2 proved to be the method of choice in this case. It is worthwhile to note that adduct 160, already utilized in the synthesis of 154, also turned out to be useful as an advanced intermediate for the preparation of 167. 

The photochemical transformations of vinylcyclopropanes are of mechanistic interest, but because of the high energy of the reaction intermediates, especially in the triplet manifold, practical applications are scarce. The regio- and stereo-selective aspects are, however, similar to those of the thermal processes. Additional methods that provide for the cyclopentene rearrangement involve the degenerate photochemical rearrangements observed by Wender during meta-photocycloaddition of arenes and alkenes and utilized extensively in the synthesis of triquinane sesquiterpenes. -" -" (See Section 8.1.9 or ref. 41 for a recent summary.)... 

Hudlicky developed a general method of triquinane synthesis based on a cyclopropanation- arrange-ment sequence of dienic diazo ketones (Scheme 52). Topological selectivity of linear versus angular triquinane synthesis has been achieved. ... 

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