Synthetic organic and organometallic chemistry: Mechanism of enyne metathesis, synthesis of natural products, metathesis cascades as complexity-building reactions
572 Natural Sciences Complex
Buffalo NY, 14260
Phone: (716) 645-4208
Fax: (716) 645-6963
Organic synthesis, catalysis and enyne metathesis
Research in my group centers around the development of new synthetic methods to synthesize molecules that have unique biological properties. A major theme in our group is the efficient construction of complex molecules using transition metal catalysis. Complex usually means lots of stereochemistry and rings. In the past several years at UB, we have been interested in a simple reaction that forms a versatile functional group, the conjugated diene. This remarkable reaction takes place between alkenes and alkynes (eq 1). This coupling process is mediated by ruthenium carbenes and is known as enyne metathesis. The carbenes shown at the bottom of the Scheme are the Grubbs’ carbenes. The Nobel Prize was awarded to Grubbs, Schrock and Chauvin in 2005 for the development of olefin metathesis.
Inquiry in the Diver group is organized around three fundamental interests that build off one another. First, we are developing new synthetic reactions. Second, we are applying these new methods to the synthesis of challenging structures. Often these are ring systems or functional group arrays that are commonly found in natural products. Last, we like to know how new reactions work. We like to remind ourselves that organic synthesis is not perfected and we don’t know everything. In fact, this is what makes synthesis with transition metals fun, that we sometimes discover something new that we didn’t expect. This three-pronged inquiry into reactivity and how reactions work has proven to be exciting and provides an excellent training program that breeds creative and independent scientists.
Organic Synthesis is Rewarding
Developing new reactions is exciting and one of the most enjoyable parts of academic research. One reaction we have recently developed is a cyclodiene ring synthesis based on tandem metathesis (eq 2). A ring is created through a series of metathesis reactions, all occurring in a single step. This efficient approach to ring synthesis has paved the way to new projects that use tandem reactions besides metathesis.
The reactions we develop are often inspired by complexity found in natural products. We like to apply our methods towards these structures or their complex substructures to illustrate the effectiveness and breadth of the chemistry (eq 3).
New Reactivity is Inspiring
In the course of ‘normal’ research, we have discovered new reactions too. Cyclopropanation is a very rare reactivity mode for ruthenium carbenes (eq 4). Organometallic catalytic methods are extremely powerful for building molecular complexity. Depending on choice of catalyst, we can make two different products. We are now developing reactions that are inspired by this reactivity to make more complex ring systems.
Rapidly stopping enyne metathesis has shed insight into ruthenium carbene reactivity. The CO-promoted reaction gives a novel insertion into the N-heterocyclic carbene ligand. Based on this, we modified the additive to design a protocol to efficiently clean up metathesis reactions.
Catalysis and Organometallic Synthesis
Catalysis is difficult to study. Yet we weren’t satisfied with our level of understanding for catalytic enyne metathesis. We felt that improved knowledge would help us design new reactions. We started a collaborative project with Professor Keister to study the mechanism of enyne metathesis. We have developed a good working hypothesis, and plan to continue to study aspects of catalysis including catalyst decomposition and chelation. Future studies here will also require the synthesis of new ruthenium carbene complexes such as those containing novel cyclophane N-heterocyclic carbene ligands for enhanced selectivity in metathesis.