A SYNTHETIC STUDY ON (+ -)-PODOSPORIN-A

The synthesis of common skeleton of podosporin A and aureol was studie d through cationic olefin cyclization as a key step. The generation of thermodynamic silyl enol ether or enol acetate under known conditions gave regioselectivity of 88:12. The enolate alkylation of 2,3-dimethy lcyclohexanone with 2,5-dimethoxybenzyl bromide at the more substitute d site via lithium enolate gave poor yield. In this case an organozinc ate or an ammonium enolate also proved to be ineffective or not practi cal in terms of yield. Side chain elongation of the substituted cycloh exanone 13 through Grignard reaction, Wittig reaction, or Shappiro rea ction did not proceed because of steric hindrance and side reactions. However, Stille coupling reaction via enol triflate produced the desir ed product 18 in high yield. The advanced intermediate 22, which was e fficiently synthesized from 18, produced 24 instead of the desired pro duct under a cationic olefin cyclization condition, indicating that th e cyclization occurred in a stepwise manner via the organomercury inte rmediate 23.