Comforth model synthesis

An ample evidence that the earlier described models that are based on the full consideration of a- and p-substituents on the aldehyde are oversimplified can be evidenced by the reported synthesis of swinholide by Paterson et al. [6]. In their synthesis, a simple alteration in the configuration at Y-position changes completely the facial selectivity of the enol nucleophile. As shown in Scheme 2.104, equation A, FeUcin control minimization of yn-pentane interactions and application of the Comforth-Evans transition state lead to a reinforced FeUdn attack. On the other side, just changing the aforementioned configuration (B) leads to yn-pentane interactions between the methyl groups at C4 and C2 and ultimately to a non-FeUdn transition state (Scheme 2.104). 

---