School of Pharmacy UNIVERSITY OF WISCONSIN - MADISON Chemistry of Allenamides and Ynamides Synthetic Methods Using Chiral Allenamides and Ynamides We are developed two unique classes of organic building blocks or organic synthons: Chiral allenamides and ynamides. These electron deficient chiral variants of allenamines and ynamines are thermally more stable and experimentally easier to handle than traditional allenamines and ynamines, thereby rendering them more synthetically useful and adaptable to reaction designs such as intramolecular manifolds and transistion metal meadiated transformation that are not possible for allenamines and ynamines. These synthons are currently being applied to a diverse array of stereoselective synthetic methodologies raning from classical pericyclic transformations to transition metal mediated reactions. A. The Chemistry of Allenamides Most significantly, we have pioneered a tandem epoxidation and oxyallyl cation [4 + 3] cycloaddition using chiral allenamides. The epoxidation of allenamides proves to be an excellent source of chiral, nitrogen stabilized oxyallyl cations. We were able to develop highly regio- and stereoselective inter- and intramolecular oxyallyl cation [4 + 3] cycloadditions. Recently, not only were we able to achieve the first asymmetric [4 + 3] cycloaddition using copper-bisoxazoline systems, but more significantly, in collaboration with Professor Ken Houk at UCLA and Dr. Elizabeth Krenske at University of Melbourne, we are beginning to construct a theoretical model for understanding and predicting regioselectivities of [4 + 3] cycloadditions, which has been unexplored. These activities have allowed us to contribute significantly to a 50-year old cycloaddition reaction. B. The Chemistry of Ynamides We have evolved the chemistry of ynamides into a burgeoning field with the following of many research groups around the world. Our work has rekindled the interest of the synthetic community toward this very interesting class of functional group. 16 Years ago, we placed particular emphasis on developing a highly efficient synthesis of ynamides in order to provide the kind of accessibility that may allow the community to view ynamides as a user-friendly functional group in organic synthesis. Toward this goal, we developed a Cu(II)-catalyzed C-N bond formation involving sp-hybridized carbons. This catalytic amidation provides a direct entry to chiral ynamides via N-alkynylation of amides. Our work and those that followed including my colleague Shannon Stahl’s beautiful work have had a huge impact on the field, allowing many research groups to freely develop methods of their interest using ynamides as an organic functional group. Recently, we were able to finally succeed in developing an ynamide version of Ficini’s thermal [2 + 2] cycloaddition with alpha,beta-unsaturated carbonyl systems.