Bromination of 2,2,6-Trialkyl-1,3-dioxan-4-ones. Application of the Deuterium Isotope Effect to the Synthesis of a Chiral Trialkyldioxinone

Article abstract of DOI:10.1021/jo00048a039

Free-radical bromination (2 equiv of NBS) of 2-tert-butyl-2,6-dimethyl-1,3-dioxan-4-one (6a) gives the 2-bromomethyl product 7a.By contrast, bromination of 2-tert-butyl-2-methyl-1,3-dioxan-4-one (1) is reported to occur at the 6-position.Deuterium-labeling experiments established that 7a is formed by direct substitution at the 2-methyl group of 6a and not by abstraction of H-6 followed by hydrogen atom transfer from the 2-methyl group and bromination of the resultant primary radical 12.When 2-tert-butyl-6-methyl-2-(methyl-d3)-1,3-dioxan-4-one (13) is reacted with 4 equiv of NBS, the course of the reaction is altered dramatically and the major product formed in high yield is dioxinone 16.Thus, a trideuteriomethyl group directs bromination away from the 2-methyl site to H-6.Bromination at the 6-position followed by the loss of HBr, addition of Br2, and loss of a second HBr gives 16.Dioxinone 14, a valuable substrate for asymmetric induction studies, is formed in high yield by reductive debromination of 16.When (R)-3-hydroxybutyric acid is used in the preparation of 13, optically pure (-)-14 is obtained using the sequence described.