Reactions of Arynes and Other Reactive Intermediates

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Professor Daesung Lee of University of Illinois at Chicago (UIC) is studying new reactivity of reactive intermediates known as arynes and developing new synthetic methods for forming these intermediates. Suitably designed organic compounds can undergo structural reorganization by heating to form new chemical species.

These synthetic methods will allow for efficient synthesis of organic compounds that have potential value in chemical biology and medicinal chemistry. Exploring these new reactive aryne species and their subsequent chemical transformations will help chemists better understand the factors and principles that facilitate the formation of these high energy species and their reactivity patterns.

An additional potential benefit of this research is that the synthetic approaches postulated herein, if successful, could spur related investigations in other systems. The simple design principles and mode of performing the reaction--under purely thermal conditions at relatively low temperatures--will allow participation of high school and undergraduate students in this research project, which will increase the opportunity of recruiting students from under-represented groups at UIC (Connect with UIC Faculty program) and high school students in Chicago area (STEM Professionals as Resource Knowledge Program of Stevenson High School).

Daesung Lee and his students will further develop hexadehydro Diels-Alder reaction-based aryne chemistry and expand the scope of transformations of other thermally generated reactive intermediates. To facilitate these thermal reactions, novel hydrogen bonding-promoted strategies will be explored and applied to the synthesis of biologically active natural products including selaginellin H, selagintamarin A, and selaginpuvilin G.

Also, the activating effect of an extra alkyne in 1,3-diynes will be examined in Alder-ene reactions, [2+2] cycloadditions between alkyne and allene, Myers-Saito and Bergman cyclizations. The activating effect of an alkyne substituent will be further exploited in the development of a new [4+2] cycloadditions to generate alpha,3-dehydrotoluene intermediates followed by their trapping as a zwitterionic or a diradical species.

This new mode of cycloaromatization is expected to display different reactivity compared to that of hexadehydro Diels-Alder reaction, thereby significantly enriching the array of thermal transformations available to multiynes. Broader impacts of this project will involve various aspects of mechanistic study, natural product synthesis, and development of medicinal and pharmaceutical lead compounds that can serve as an ideal platform for student training at various levels, including undergraduates, graduate students, and postdocs.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.