DFT study on the mechanism and stereochemistry of the Petasis-Ferrier rearrangements

The Petasis-Ferrier rearrangement is a very important and useful reaction for the synthesis of multifunctional tetrahydrofurans and tetrahydropyrans from easily synthesized enol acetals. Here we report our DFT investigation of the detailed reaction mechanism of the Petasis-Ferrier rearrangement, proposing that the active promoting species in this reaction is the cationic aluminum species, instead of the usually considered neutral Lewis acid (this will give very high activation energies and cannot explain why the Petasis-Ferrier rearrangements usually take place at low temperature or under mild conditions). Calculations indicated that the mechanisms of the Petasis-Ferrier rearrangements for the formations of five- and six-membered rings are different. Formation of five-membered tetrahydrofuranone is stepwise with C-O bond cleavage to generate an oxocarbenium enolate intermediate, which then undergoes an aldol-type reaction to give the desired cyclized oxacycle. In contrast, the formation of six-membered tetrahydropyranone is a concerted and asynchronous process with the C-O bond breakage and aldol-type C-C bond formation occurring simultaneously. A DFT understanding of why the catalytic versions of the Petasis-Ferrier rearrangements cannot be realized when using R2Al(+) as the active promoting species has also been discussed. In addition, DFT calculations were used to reveal the origins of the stereochemistry observed in the Petasis-Ferrier rearrangements.