Annulation triquinane synthesis

N. Naz, T. H. Al-Tel, Y. Al-Abed, and W. Voelter, Synthesis of polyfunctionalized bis-annulated pyranosides Useful intermediates for triquinane synthesis, Tetrahedron Lett. 35 8581 (1994). 

INTRAMOLECULAR (2+2) CYCLO-ADDmONS OF KETENES AND VINYLKETENES TO OLEFINS. 3. THE SYNTHESIS OF ANGULAR ANNULATED TRIQUINANE DERIVATIVES. 

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]. 

This concept has been applied for the synthesis of the structurally complex and highly oxyfunctionalized triquinane (—)-coriolin (Sch. 31) [61]. Two carbonyl groups, both in the right position for 1,2-acyl shift were present in the trimethyl-functionalized bicyclo[2.2.2]octenone 58. With a site-selectivity of 85% the expected regioisomeric tricyclic dione 59 was formed as a mixture of epimers (Sch. 31). Subsequent transformations involving the annulations of the third five-membered ring as well as epoxidation and hydroxylation steps led to the desired natural product... 

An elegant synthesis of ( )-hirsutene (32) was developed by Cohen and coworkers . The key step of the synthesis is the one pot, completely stereoselective, oxidative cyclopen-tannulation of dienolate 31 with two equivalents of FeCls in dmf (equation 17). CuCl2 was also tested, but proved inferior. The formation of a single diastereoisomer of the triquinane intermediate (31 ) is useful and suggests that stereochemical equilibration may occur at some stage. This annulation procedure can also be extended to cyclohexanone enolates. 

Although a number of syntheses of the angular triquinane sesquiterpene isocomene (18) have now been published, the synthesis by Dreiding et al. is interesting since it features the sequential alkynone cyclisations (14)— -(15) and (16)——(17) as the two key 5-ring annulation reactions. In a new synthesis of the related sesquiterpene silphinene (23) intramolecular(2+2] photocycloaddition from (19) is first used to elaborate the tricycle (20), which on brief exposure to iodotrimethylsilane produces (21). Reduction of (21) to (22), and functional group elaboration then completed the... 

One particularly elegant use of the silicon-directed Nazarov cyclization was in the synthesis of the angular triquinane silphinene (89), by Miesch and co-workers. Addition of a large excess of boron trifluoride etherate in refluxing ethylbenzene to 86 ensured annulation of the required third ring. Notably, the benzyloxy group was also eliminated imder the reaction conditions, and the product 88 was subsequently converted into the natural product 89. 

Hudlicky T, Short RP (1982) Terpenic Acids by Cyclopentane Annulation of Exocyclic Dienes. Synthesis of Triquinane Portion of Retigeranic Acid. J Org Chem 47 1522... 

Singh, V. and Jagadish, B., Synthesis of exo-annulated bicyclo[2.2.2]octenone and its oxa-di-Jt-methane rearrangement to cisisynxis triquinane, Indian J. Chem., 35B, 401,1996. 

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