Unexpected migration and oxidative cyclization of substituted 2-acetophenone triflates under basic conditions: synthetic and mechanistic insights.
Oxidative ring closure of alkyl-substituted 2-hydroxyacetophenone trifluoromethanesulfonate esters (triflates) occurs upon exposure to base in anaerobic DMF at 20-90 degrees C. Alkyl substitution is required for ring closure. A migrated enol triflate product forms at lower temperature in high yield via migration of the trifluoromethanesulfonate in the unsubstituted and monoalkyl-substituted cases. The alkyl-substituted enol triflates also enter into the benzofuran-3-one ring-forming process under thermal cyclization conditions. Potential mechanistic pathways are evaluated.
Coe
Jotham W
JW
Pfizer Global Research and Development, Groton Laboratories, Pfizer Inc., Groton, Connecticut 06340, USA. coejw@groton.pfizer.com
Bianco
Krista E
KE
Boscoe
Brian P
BP
Brooks
Paige R
PR
Cox
Eric D
ED
Vetelino
Michael G
MG