Asymmetric Oxidative Cyclization of o-Phenolic Oxime-Esters: First Synthesis of Enantiomerically Enriched Spiroisoxazoline Methyl Esters.

A new method for the synthesis of enantiomerically enriched cyclohexadienone spiroisoxazoline (-)-2a has been described. Asymmetric intramolecular oxidative cyclization of the o-phenolic oxime-ester 1c using a novel optically active tertiary alcohol (-)-3 as a chiral auxiliary proceeded smoothly to afford cyclohexadienone spiroisoxazoline 2c in 83% yield. Opitcally active tertiary alcohol (-)-3 was synthesizied from racemic (1S,8R,9R,10R)-8-phenyl-1-decalol (4) by optical resolution. Removal of the chiral auxiliary in 2c with CF(3)COOH followed by methylation gave methyl ester (-)-2a in 74% ee (71% chemical yield) having S-configuration. The absolute configuration of 2awas determined by the synthesis of the marine natural product (+)-aerothionin.