Event Information
Novel Methods for Alpha-Functionalization of Ketones and Thioesters
- Abstract:
Carbon–carbon bond-forming reactions comprise the most important class of synthetic transformations practiced in the modern pharmaceutical industry and in government and academic laboratories throughout the world. These reactions have significant and wide-reaching implications in many areas, but are most notable in the development and synthesis of new and existing pharmaceutical products. We have been exploring soft enolization as a means of enabling certain key carbon–carbon bond-forming reactions in an effort to establish mild, operationally simplified and inexpensive alternatives to the existing conventional approaches. For example, ketones were found to undergo soft enolization and acylation on treatment with MgBr2•OEt2, i-Pr2NEt and various acylating agents to give 1,3-diketones. The processes is particularly efficient for N-acylbenzotriazoles and O-Pfp esters and, in these cases, can be conducted using untreated, reagent grade CH2Cl2 under atmospheric conditions, thus providing an exceptionally simple approach to the synthesis of this important class of compounds. The methodology has also been extended to the preparation of -keto thioesters through the development of a direct crossed-Claisen reaction involving thioester enolates.
We will also describe a novel approach to -functionaliztion of ketones that proceeds via conjugate addition of various nucleophilic carbon species to diazoalkenes derived in situ from the corresponding sulfonyl hydrazones. This method offers a fundamentally different way of approaching ketone -functionalization based on umpolung reactivity and, consequently, enables the incorporation of functionality not possible using standard methods employing ketone enolates.
Master's Thesis Defense Seminar
Student Exams Seminar