Use of an Axial α-Face Control Element in Intramolecular Conjugate Additions: Synthesis of an ABCD Tetracyclic Bruceantin Precursor

Article abstract of DOI:10.1021/jo00356a030

An ABCD ring intermediate for the synthesis of the quassinoidal antileukemia agent bruceantin has been prepared.Control of stereochemistry of the C ring fusion has been established by a cesium fluoride mediated intramolecular conjugate addition of an α-face α-sulfonyl ester to an α-chloro enone (49); the product from this reaction is a pentacyclic cyclopropyl sulfone (60).Reductive silylation of this sulfone affords a regiospecific silyl enol ether (64) which can be converted to the natural BC ring stereochemistry by oxidative cleavage followed by intramolecular aldol reaction (64 to 69).A new method for the oxidative ring expansion of δ-lactones to α-keto δ-lactols is demonstrated.The procedure involves the conversion of a tertiary lactol to a β-methylthio exocyclic enol ether by the action of the Swern reagent (74 to 75 and 84 to 85); further oxidation of these β-methylthio enol ethers with osmium tetraoxide directly affords the ring-expanded α-keto lactols (86, 87).