Hydroazulene skeleton

Cycloaddition involving the Pd-catalyzed trimethylenemethane (TMM) fragment 63 and the 1.3-diene 61 with an EWG offers a good synthetic method for the hydroazulene skeleton 65. The cydoaddition of trimethylene-... 

Desymmetrization of a seven-membered cyclic meso compound, followed by a metallo-ene reaction, provides ready access to the trans-hydroazulene skeleton (Scheme 8E.15) [69]. By using BINAP in preference to BINAPO ligand, which gave a lower enantioselectivity (70% ee), two alkylation products were obtained in differential enantioselectivities. The high enantiopurity of the major product 106 may be the consequence of a subsequent kinetic resolution because the second ionization, followed by proton loss from enf-106, involved a matched event. 

This ring expansion procedure was extended to the preparation of a functionalized hydroazulene skeleton . 

Further transannular cyclization studies start from (E)- or(Z)-5-cyclodecenone while radical-induced reactions form hydroazulene skeletons predominantly, the acid-catalyzed reactions generate hydronaphthalene systems. Only 1,6-cyclization products are observed, the L -config-urated cyclodecenone leads to the tram, while the Z-configurated material yields the cis ring... 

A 1,5-distance between the initiating cation and nucleophilic center of the double bond (resulting from Markovnikov s rule) generates a hydroazulene skeleton. Formation of a cis ring junction is favored but there are several examples producing ra j-fused systems. In many cases mixtures of cis- and tram-hydroazulenes are found55. 

A third skeletal system which occurs widely in natural products is the hydroazulene skeleton. The /rans-annulated form seems to be somewhat more stable than the corresponding nix-form41- 48. Thus, isomerization of compounds such as 1 can be easily achieved in alkaline media and the equilibrium is largely in favor of the trans-fused product49. 

An attractive synthesis of the hydroazulene skeleton of the fungal sesquiterpene velleral (168) has been reported, based on the known addition of dimethyl acety-lenedicarboxylate to an enamine, viz. (166), followed by electrocyclic ring-opening of the resulting cyclobutene, viz. (167) (Scheme 31). ° The potentially useful hydro-... 

It is possible to effect an anti-Markovnikov cyclization to the per-hydroazulene skeleton of the guaianes by the action of acid catalysts upon the 5,6-epoxides of various germacrene sesquiterpenes (727, 124). Markovnikov opening of the epoxode with participation of the transannular double bond (cyclobutane-like strain in transition state) does not compete. For contrast, the cyclization of the isomeric epoxide to eudesmanediol is also shown. 

Transannulation reactions involving triple bonds59 or allenic units60 are known. The major products are mostly decalin skeletons but hydroazulene formation is also found. Stereoselection regarding the ring junction is low and in some cases Wagner-Meerwein rearrangements lead to constitutional isomers. 

The oxabicyclo[3.2.1]octan-2-one ring systems form a core skeleton of many naturally existing molecules. In an approach towards guaianolide sesquiterpenes, their hydroazulenic framework has been constructed through a rhodium(II)-catalyzed reaction [82] of the a-diazo ketone 106 with DMAD to afford the oxatricyclic system 107, which forms the skeleton of ambrosic acid 108 (Scheme 33). 

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