Development and application of nonracemic cyclohexa-2,5-dienones in the total synthesis of (+)-epoxysorbicillinol and (+)-rishirilide B

A vast number of structurally intriguing biologically active compounds have been isolated from nature. The reactive nature of these compounds is in part responsible for their biological activity. One biosynthetic intermediate is typically responsible for an entire family of bioactive compounds. Unlike nature, however, most asymmetric total syntheses focus on developing methods that are typically limited to one specific molecule. Following natures suggestion, we envisioned that a method for the procurement of nonracemic cyclohexa-2,5-dienones would be useful for the synthesis of numerous molecules. The versatility of a cyclohexa-2,5-dienone constructed from the dearomatization of resorcinol derivative stems from the embedded electronically differentiated olefins.; A method for the synthesis of nonracemic cyclohexa-2,5-dienones was developed. The dearomatization leading to nonracemic cyclohexa-2,5-dienones used an economical chiral directing group derived from methyl lactate. Unlike most dearomatizations, this dearomatization protocol provides the desired cyclohexa-2,5-dienones in good yields. The method proves to be general and can therefore be useful for the synthesis of numerous cyclohexa-2,5-dienones. In addition, several methods to remove the directing group were developed. The total synthesis of (-)-rishirilide B was completed using a chiral cyclohexa-2,5-die none assembled using the method. In addition, significant advances were made towards the synthesis of (+)-epoxysorbicillinol.