Brown Lab
Indiana University

The Brown group is focused on the development of new methods and strategies for organic chemical synthesis. Inspiration for problem selection comes from the structures of important molecules that are currently difficult, or impossible, to access with current technologies. Our group is broadly interested in three research areas: 1) Stereoselective [2+2] cycloaddition to prepare cyclobutanes, 2) Cu-catalyzed cross-coupling/interrupted cross-coupling reactions, and 3) stereoselective cross-coupling of Csp3-nucleophiles by Pd/Cu synergistic catalysis.

■  Stereoselective [2+2] Cycloadditions

Our lab seeks to invent reagent or catalyst controlled stereoselective [2+2] cycloadditions of alkenes with allenes or heteroallenes. The substituted cyclobutanes generated by these transformations are either directly found in bioactive molecules or can be subjected to a wide variety of complexity-building chemical reactions to quickly establish complex polycyclic molecular frameworks.

 

■  Transition Metal-Catalyzed Cross-Coupling Reactions

The value of transition metal-catalyzed cross-coupling reactions in the chemical synthesis of important molecules cannot be underestimated. Within this area our lab is broadly interested in two major themes: 1) Cu-catalyzed Suzuki-type cross-couplings/interrupted cross-couplings, and 2) stereoselective cross-coupling of Csp3-nucleophiles.

1) Stereoselective Cross-Coupling of Csp3-Nucleophiles.

Traditional strategies for stereoselective cross coupling of Csp3-nucleophiles involve the pregeneration and often the isolation of the chiral nucleophilic component. We envisioned a different approach to the problem that involves catalytic generation of Csp3-organometallic nucleophiles in situ by addition of Ln[M]-G (Bpin, H, Ar, etc.) complexes across simple alkenes followed by cross-coupling. The approach has several notable advantages: 1) Simple alkenes are used as the chemical input. 2)  Both positions of the alkene are functionalized, thus allowing for two new bonds (up to two stereocenters) to be generated in a single step. 3) An additional site for further functionalization can be incorporated. 4) Pregeneration and isolation of the Csp3-nucleophile is not necessary.

2) Cu-Catalyzed Suzuki-Miyaura Type Cross-Couplings

Our lab is interested in developed practical Cu-catalyzed Suzuki-Miyaura type cross-couplings. Our efforts in this area are not driven purely by cost and toxicity benefits with Cu, but also by the discovery of new reactivity that will allow for the synthesis of important molecules that were previously difficult to access. One major emphasis in this area is to utilize the unique reactivity of Cu to achieve alkene functionalization through interrupted cross-coupling.