Annelation-ring cleavage 3 + 2 Annelations

The chemistry of thiopyrylium salts and their annelated congeners is dominated by the electrophilicity, of the cationic nucleus. Nucleophilic attack is formally the reverse of the principal means of synthesis (elimination of a suitably disposed group), though further reaction can lead to ring cleavage, and, in appropriate cases, to ring closure to alternative heterocycles. 

Annelation-ring cleavage.1 A bifunctional reagent with an acetal and an allylsi-lane group can be used for annulation of silyl enol ethers to six- and seven-membered carbocycles (equation I).2 The reaction involves conjugate addition to give an adduct that undergoes intramolecular cyclization. 

A novel entry to decahydrocyclopentacyclooctene derivatives via the intramolecular photocycloaddition of fused a,/3-unsaturated y-lactones has been developed (80CC1011). Irradiation of the butenolide (153) in acetone solution gave both the fused and bridged photoadducts (154) and (155) (2-3 1). The major adduct was hydrolyzed, oxidized and esterified to afford (156). Reductive cleavage of the unsaturated keto ester (156) with lithium in ammonia afforded a five-component mixture of a,/3- and /3,y-unsaturated esters. Equilibration with 0.1M sodium methoxide in methanol converted the mixture into a single a,j8-unsaturated ester (157 Scheme 34). This annelative two-carbon ring expansion method may find application in the synthesis of ophiobolin and ceroplastol sesterterpenes. 

Intramolecular addition of thiolate, dithiocarboxylate, and enedithiolate sulfurs to unsaturated carbon-carbon bonds also provides a convenient way to thiophenes. Thus, reductive cleavage of the thioester group of the compound (11) followed by intramolecular addition of the thiolate sulfur to the triple bond affords the thiophene (12) directly (Equation (2)) <93SL209>. In this way, a number of alkyl-substituted and six-membered ring annelated thiophenes were synthesized in good overall yields. 

The stereogenic centers were then introduced by palladium-catalyzed dynamic kinetic asymmetric transformatitHi. ITierefore, 41 was coupled with lactone 42 in the presence of chiral ligand (RJt)-43 and gave 44 in 89% yield. The synthesis of 42 is shown below in Scheme 2.6. Compound 44 was subjected to an intramolecular Heck reaction followed by acidic cleavage of the ester function 45). The intramolecular Heck reaction only produced one diastereomer, because the c/s-annelated rings are favored. Scandium(lll)-mediated cyclizatitMi and reduction of the lactone with DIB ALII yielded (-)-aflatoxin Baa (46). It was acetoxylated and then pyiolyzed to give (-)-aflatoxin Bi (1) in 1.6% overall yield and nine linear steps from catechol (40). 

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