An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition–lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry
Young, C., Taylor, J., & Smith, A. (2019). Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition–lactonisations. Organic and Biomolecular Chemistry, 17(19), 4747-4752. https://doi.org/10.1039/C9OB00703B