Protoilludane synthesis

Intramolecular [2 + 2 + 2] cycloadditions belong to the same type of valence isomerization as those of 1,5-unsaturated compounds to cyclobutanes.70 The cobalt-mediated cyclization of l-en-5-ynes stereoselectively converts enediynes directly to bicyclo[4.2.0]hexa-l,3-dienes, as single diastereomers, when a stoichiometric amount of dicarbonyl(cyclopentadienyl)cobalt is used. This cyclization90 has a high efficiency (92%). An example is the synthesis of the protoilludane framework 23 from the enediyne precursor 22.71... 

Singh, V. and Porinchu, M. (1996) Sigmatropic 1,2- and 1,3-acyl shifts in excited states a novel, general protocol for the synthesis of tricyclopentanoids and protoilludanes. Tetrahedron, 52, 7087-7126. 

An expeditious stereospecific synthesis of the protoilludane skeleton has been actively pursued by Matsumoto s group. In his first approach (Scheme 42),307 bicyclooctanone 274 was smoothly elaborated in classical fashion. Using a five-step sequence to effect a 1,2-carbonyl transposition with retention of a hydroxyl group at the original carbonyl site, these workers then prepared 275. Oxidation of this intermediate followed by end acetylation afforded 276. When this enone was irradiated... 

A number of compounds with the protoilludane skeleton have been synthesized (Scheme 40). The two keto-esters (279) and (280) have been converted by standard methods into a variety of tricyclic analogues. In addition, the bicyclic enone (281), obtained from 4,4-dimethylcyclopentene and acetyl-acetone by a similar procedure, has been converted into protoillud-7-ene (282) (Scheme 41). A long and rather low-yield synthesis of (283), a possible precursor of illudinine (284), has been reported. ... 

Attempts to devise a biogenetic-type synthesis of hirsutene (314) and derivatives cf. Vol. 7, pp. 79,80) have recently culminated in the successful conversion of protoilludane epoxide (315) into hirsUten-8a-ol (316) and compounds (317)— (319). In contrast the diastereomeric epoxide (320) under the same conditions (Bp3,Et20) provides the ketone (318) as the only product (Scheme 30). 

Schwartz BD, Matousova E, White R, Banwell MG, Willis AC (2013) A chemoenzymatic total synthesis of the protoilludane aryl ester (+)-Armillarivin. Org Lett 15 1934-1937... 

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