Water Overcomes Methyl Group Directing Effects in Epoxide-Opening Cascades

Journal of the American Chemical Society 131(19), 6678-6679, DOI: 10.1021/ja9025243

Water is an effective promoter of the endo-selective opening of trisubstituted epoxides, enabling related cascades leading to a variety of substituted ladder polyether structures. When used in conjunction with a tetrahydropyran-templated nucleophile, water can overcome the powerful electronic directing effect of a methyl substituent at either site of the epoxide, making water a uniquely versatile medium and promoter of epoxide opening.