A drawback of this biosynthetic hypothesis is that when treated with either acid or base, simple disubstituted epoxy alcohols cyclize to favor the undesired exo products. A breakthrough occurred when our group discovered that if a tetrahydropyran (THP) ring template was formed prior to the epoxide cyclization, the desired endo product was obtained in a 10:1 endo/exo ratio simply by heating the substrate in neutral water. This effect could be carried directly into multi-epoxide cascades – the first time that an endo-selective nucleophilic cascade of unbiased epoxides had ever been observed.
- Morten, C. J.; Byers, J. A.; Jamison, T. F. “Evidence that Epoxide-Opening Cascades Promoted by Water are Stepwise and Become Faster and More Selective After the First Cyclization” J. Am. Chem. Soc. 2011, 133, 1902-1908. Download PDF
- Morten, C. J.; Byers, J.A.; Van Dyke, A.R.; Vilotijevic, I.; Jamison, T. F. "The Development of Endo-Selective Epoxide-Opening Cascades in Water" Chem. Soc. Rev. 2009, 38, 3175-3192. Download PDF
- Morten, C. J.; Jamison, T. F. "Water Overcomes Methyl Group Directing Effects in Epoxide-Opening Cascades" J. Am. Chem. Soc. 2009, 131, 6678-6679. Download PDF
- Byers, J. A.; Jamison, T. F. " On the Synergism Between H2O and a Tetrahydropyran Template in the Regioselective Cyclization of an Epoxy Alcohol" J. Am. Chem. Soc. 2009, 131, 6383-6385. Download PDF
- Vilotijevic, I.; Jamison, T. F. "Epoxide-Opening Cascades Promoted by Water" Science 2007, 317,1189-1192. Download PDF
- Simpson, G. L.; Heffron, T. P.; Merino, E.; Jamison, T. F. "Ladder Polyether Synthesis via Epoxide-Opening Cascades Using a Disappearing Directing Group" J. Am. Chem. Soc. 2006, 128, 1056-1057. Download PDF