text: In the first enantioselective synthesis of (+)-Griseofulvin, a potent antifungal agent, a Curtin–Hammett situation was observed. A key step in the synthesis is the rhodium-catalyzed formation of an oxonium ylide, which then undergoes a [2,3] sigmatropic rearrangement en route to the desired product. However, the substrate contains two ortho-alkoxy groups, either of which could presumably participate in oxonium ylide generation.
  Obtaining high selectivity for the desired product was possible, however, due to differences in the activation barriers for the step following ylide formation. If the ortho-methoxy group undergoes oxonium ylide formation, a 1,4-methyl shift can then generate an undesired product. The oxonium ylide formed from the other ortho-alkoxy group is primed to undergo a [2,3] sigmatropic rearrangement to yield the desired compound. Pirrung and coworkers reported complete selectivity for the desired product over the product resulting from a 1,4-methyl shift. This result suggests that oxonium ylide formation is reversible, but that the subsequent step is irreversible. The symmetry-allowed [2,3] sigmatropic rearrangement must follow a pathway that is lower in activation energy than the 1,4-methyl shift, explaining the exclusive formation of the desired product.