Triquinane skeleton

Scheme 6/4.15. Nickel-mediated formation of the triquinane skeletons.

An additional prerequisite in this reaction, however, is inhibition of a premature P-hydrogen elimination. Reaction of 6/4-56 and 6/4-57 led to 6/4-58 with 41 % yield. Again, one can assume that first a Ni-complex 6/4-59 is formed, which gives the bicyclic 6/4-60 followed by formation of the triquinane skeleton 6/4-58 via 6/4-61 with a P-hydride elimination being the last step (Scheme 6/4.15). 

Persistent synthetic efforts toward the triquinane skeleton through the intramolecular PKR have appeared in the literature. These include synthesis of (T)-ceratopicanol by Mukai, synthesis of the tricyclic moiety in kalmanol by... 

Hua has used the products of Pauson-Khand cycloadditions for syntheses of optically active pental-enene and racemic pentalenolactone E methyl ester. The racemic ketone in the first case was converted to the necessary optically active intermediate by kinetic resolution via 1,4-addition of an optically active allyl sulfoxide anion. These represented the first synthesis of natural products containing the angularly fused triquinane skeleton from bicyclic Pauson-Khand products (equation 53 and Scheme 20). ... 

Scheme 7-59 Access to linear or angular triquinane skeleton.

During the enantioselective total synthesis of (-)-coriolin, I. Kuwajima and co-workers used a Darzens-type reaction to construct the spiro epoxide moiety on the triquinane skeleton. Interestingly, the usual Darzens condensation where the a-bromoketone was condensed with paraformaldehyde yielded a bromohydrin in which the hydroxymethyl group was introduced from the concave face of the molecule. This bromohydrin upon treatment with DBU gave the undesired stereochemistry at C3 (found in 3-ep/-coriolin). To obtain the correct stereochemistry at C3, the substituents were introduced in a reverse manner. It was also necessary to enhance the reactivity of the enolate with potassium pinacolate by generating a labile potassium enolate in the presence of NIS. The in situ formed iodohydrin, then cyclized to the spiro epoxide having the desired stereochemistry at C3. 

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]. 

Scheme 12. 0-Stannyl ketyl approachs to triquinane skeletons...

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... 

It is noteworthy that, although Pd-catalyzed zipper mode cyclization under the Heck reaction conditions has widely been used for the construction of polycyclic systans, it would not be suitable for the construction of the capnellene skeleton with the cis-anti-cis stereochemistry, since the Heck reaction involves syn addition of an organopaUadium species to the carbon-carbon double bond followed by the syn elimination of a palladium hydride. Indeed, only the cis-syn-cis triquinane skeleton would be formed, and this has indeed been the case.f" ... 

Enholm EJ, Jia ZJ. Synthesis of linear and angular triquinane skeletons by 0-stannyl ketyl-promoted fragmentation-cyclization reactions of a-keto cyclopropanes. J. Org. Chem. 1997 62(1) 174-181. 

Jiao, L., Yuan, C. and Yu, Z.-X. (2008) Tandem Rh(l)-catalyzed [(5- -2)- -l] cycload-dition/aldol reaction for the construction of linear triquinane skeleton total syntheses of ( )-hirsutene and ( )-l-desoxyhypnophilin. Journal of the American Chemical Society, 130(13), 4421 430. 

This strategy has been used in one step to construct an angular triquinane skeleton [180]. 

Cydopentenone 64 bearing a carbonyl group in the substitutent R may serve for the synthesis of the angularly fused triquinane skeleton 66 based on a double Michael addition to the cyclopentadienone generated via base-promoted elimination of the dialkylamine [45]. Spiro[4.4]nonenone 65 appears as the relevant intermediate from the first Michael addition. Biscyclopentannulated cyclobutane 67... 

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