The ability to design and synthesize new molecules are tools of enormous power that chemists bring to molecular level investigations in many areas of science. Research in the Overman group centers on the invention of new transformations and strategies in organic synthesis, and the total synthesis of complex organic molecules having promising biological properties. In our studies, natural products with unusual structures often play a role in pointing out limitations of current chemical synthesis art, thereby stimulating us to develop new organic synthesis methods.

Invention of New Transformations.  A major focus of our research in this area is the development of catalytic reactions using organometallic catalysts. Exemplary is our recent development of the first practical catalytic asymmetric conversions of prochiral allylic alcohols to branched chiral allylic amines and esters. These catalytic asymmetric reactions employ palladacycle catalysts of the COP family, which are now commercially available.

Inventing cascade reaction sequences that form several rings with high levels of stereocontrol is another strategy we employ to design transformations of value in synthesis. Two illustrative examples are depicted below. These cascade transformations were pivotal strategic steps in our recent total syntheses of the marine diterpene briarellin E and the structurally intricate Stemona alkaloid didehydrostemofoline.

Natural Product Total Synthesis.  At any one time, the Overman laboratory is engaged in the total synthesis of a dozen or more structurally distinct natural products. Many of our recent target molecules are rare marine natural products, where synthesis has played a key role in defining the structure of these typically non-crystalline compounds. Our synthesis strategies employ transformations developed in our group as central steps. A selection of natural products recently synthesized in our laboratories is shown below.