DIASTEREOSELECTIVE 1,4-CONJUGATE ADDITION TO -SUBSTITUTED ENONES AND PROGRESS TOWARD THE TOTAL SYNTHESIS OF BRAZILIDE A

An organocatalytic enantioselective 1,4-conjugate addition to enones that controls the absolute stereoselectivity of the chiral center generated at the -position of the carbonyl has been developed. The inclusion of -substituents in the enone adds a new chiral center, and a diastereomeric relationship, in the product as shown in Scheme 1. Therefore, it is desired to be able to control the diastereoselectivity of the product, leading to the formation of two chiral centers that are independently controlled in one step via an enantioselective protonation of the transient boron enolate. Brazilide A has been isolated from Sappan lignum, a traditional Chinese medicine. Only one total synthesis of brazilide A has been published due to the complexity of the propellane core. A rhodium carbene-cascade, followed with a base-catalyzed rearrangement, developed by the May lab, forms the propellane core as shown in Scheme 2. This methodology allows for a concise, and high-yielding formation of the structurally complex propellane core that will allow for a novel synthesis of brazilide A.