Abstract: Professor Porco’s research is focused in two major areas: the development of new synthetic methodologies for efficient chemical synthesis of complex molecules and synthesis of complex chemical libraries. Synthetic methodologies developed in his laboratory include: copper (I)-mediated formation of enamides, oxa-electrocyclization/dimerization of dienals enroute to complex epoxyquinoid frameworks; enantioselective oxidative dearomatization using chiral copper complexes and molecular oxygen; photocycloaddition using oxidopyryliums enroute to the rocaglamides and related natural products, and catalytic ester-amide exchange using group (IV) metal alkoxide-activator complexes. In the past six years, his research group has synthesized twenty-three complex natural product targets, including nine epoxyquinoid natural products, four salicylate enamide macrolides, the rocaglamides, and kinamycin C.

At the NIH-funded Center for Chemical Methodology and Library Development at Boston University, Professor Porco and coworkers have recently focused on approaches to identify transformations leading to complex chemotypes. Reaction development has historically been guided by problems in total synthesis or interest in developing chemical transformations of broad scope and utility. Chemical methodology development has increasingly relied on systematic evaluation of catalysts and other variables including solvent, temperature, and supporting ligands. Screening approaches have increased the efficiency of reaction development with regard to discovery of active catalysts or conditions but have generally been focused on specific transformations of interest.

An emerging but underdeveloped method for chemical reaction discovery involves high-throughput screening. A few examples have been reported in which new reactions were discovered through screening of either multicomponent systems or reaction partners and catalysts. As a part of our overall interest in the synthesis of new chemotypes and structural frameworks, we have initiated a program to identify novel chemical transformations using both “multidimensional screening” and “reaction discovery” approaches. In this approach, substrates may be reacted with various catalysts and reaction partners in an array format and analyzed for unique reaction processes. In this lecture, we will report our recent studies on this mode of reaction screening and the identification and exploration of several new transformations discovered during initial screening efforts.

Abstract: The possibility of direct and selective introduction of a new functionality or a new C-C bond via C-H bond functionalization has long intrigued organic chemists as it provides new strategic opportunities for the synthesis of complex organic compounds. In this lecture, I will describe the efforts in the Sames laboratory aimed at development of new catalytic transformations of both sp² and sp³ C-H bonds. The main focus will center on C-C bond forming reactions in the context of diverse organic substrates (e.g., C-arylation of heteroarenes and saturated heterocycles, cross-coupling of alkenes and cyclic amines, electrophilic C-H/alkene coupling triggered by intramolecular hydride transfer). Both new mechanistic insights and the synthetic scope of these processes will be discussed. I will also present recent applications of the alkyne hydroarylation method (developed earlier in our group) to the synthesis of novel neuro-imaging probes, which were designed to illuminate the dopamine neurotransmission in the brain.

Abstract: Professor Scheidt’s research has focused on the development of new catalytic reactions and the total synthesis of molecules with important biological and structural attributes. Current methodology research in the Scheidt group involves the development of catalytic multi-component coupling processes, organosilicon chemistry, and the discovery of new catalytic reactions with N-heterocyclic carbenes (NHCs). In exploring this new field of carbene catalysis, he and his research group have discovered numerous innovative approaches to carbonyl/acyl anion equivalents, homoenolate reactivity, hydroacylations of ketones, formal [3+3] cycloadditions, Michael reactions, aldol reactions, and acylvinyl anion equivalents. The overarching theme in these investigations is the discovery of new or unconventional reactivity modes that facilitate the synthesis of target molecules, utilize simple precursors, and produce minimal waste.

The total synthesis program in the Scheidt laboratory focuses on the construction of complex natural products containing oxygen heterocycles. Using new Lewis acid-catalyzed cyclization reactions with dioxinones, we are pursuing the synthesis of tetrahydropyran-containing natural products with anti-tumor activity. With our recent discovery of the first catalytic enantioselective synthesis of flavanones, our laboratory is engaged in the synthesis of this broad and important family of medically relevant compounds. This presentation will present our recent exciting discoveries of new chemical reactions using carbene catalysis and highlight our recent successful total synthesis endeavors.

Abstract: Although it has been well demonstrated that given ample time and resources, highly complex molecules can be synthesized in the laboratory, too often current methods do not allow chemists to match the efficiency achieved in Nature. The discovery and development of highly selective C—H oxidation methods, similar to those found in Nature, for the direct installation of oxygen and nitrogen functionalities into allylic and aliphatic C—H bonds of complex molecules and their intermediates will be presented. Unlike Nature which uses elaborate enzyme active sites, we rely on the subtle electronic and steric interactions between C—H bonds and small molecule transition metal complexes to achieve high selectivities. Our current understanding of these interactions gained through preliminary mechanistic studies will be discussed. Novel strategies for streamlining the process of complex molecule synthesis enabled by these methods will be presented.