Synthetic organic chemistry is the unifying feature of all research in the Coltart group. We are particularly interested in the development of new synthetic methods and the use of those methods to enable the total synthesis of structurally complex, biologically active natural products. The methodology research in our group focuses mainly on asymmetric carbon–carbon bond formation, especially the α-alkylation of carbonyl compounds. We have been developing two programs in parallel along these lines. One is based on the use of activated hydrazones and centers around achieving the longstanding, yet unrealized goal of developing a general approach to the asymmetric a-alkylation of ketones. The second focuses on soft enolization of thioesters as a mild and operationally simple alternative to conventional hard enolization procedures.
Activated Hydrazones and Oximes in the Development of New Asymmetric Methods
A major aspect of our current research effort is the study of activated hydrazones, oximes, and related compounds in the development of new asymmetric methods. The methods we are developing may be categorized according to two broad reaction manifolds: 1) those based on nucleophilic addition to N-sulfonyl azoalkenes, nitrosoalkenes, and related compounds and 2) those based on electrophilic addition to azaenolate mono- or dianions.
Direct Carbon–Carbon Bond Formation via Soft Enolization of Thioesters
One of our primary research objectives is the development of mild and operationally simple approaches to key carbon–carbon bond-forming reactions. In terms of developing mild synthetic methods, Nature’s repertoire of reactions is an ideal source of inspiration given that these reactions are conducted in an aqueous environment and, typically, under aerobic conditions. Moreover, years of evolution have led to the refinement of these transformations and much can be learned from the manner in which they are conducted. Inspired by the way in which carbon–carbon bond formation occurs in citrate synthase, we have been studying the soft enolization of thioesters as a means of developing simple approaches to certain fundamental organic transformations.
Natural Products Total Synthesis
Much of the methodology that we have developed has been, or is being applied in the context of natural product total synthesis. Often the final objective is not the synthesis of the natural product, which itself is a worthwhile and challenging goal. Instead, the completed synthesis marks the transition into biological investigations. Some targets that are either completed or in progress include the following: