Facilitated By

San Antonio Medical Foundation

Catalytic Cycloaddition Reactions and Their Applications

The University of Texas at San Antonio

The University of Texas at San Antonio is an emerging Tier One research institution with nearly 29,000 students.

Principal Investigator(s)
Doyle, Michael
Funded by
Natl Science Fdn
Research Start Date

OVERVIEW.The objective of the proposed research project is to evolve catalytic cycloaddition reactions that originate through metallovinylcarbene [3+n]-cycloaddition processes in new directions. We will develop transformations made possible with [3+n]-cycloaddition products. will advance Br??nsted acid catalyzed cycloaddition reactions for efficient. previously unattainable molecular constructions. and will use novel chiral donor-acceptor (D-A) cyclopropanes for cycloaddition that occurs with retention of configuration. The components of this objective provide convenient methodologies for facile and highly selective syntheses of complex molecular frameworks. This objective takes advantage of our ability to construct strained-ring compounds with exceptional stereocontrol that provide electronic and steric advantages in their subsequent transformations. The proposed research will open new approaches to cycloaddition transformations. broaden strain-induced ring opening for highly selective late-stage syntheses. and explore new transformations originating from these investigations.
 INTELLECTUAL MERIT.The focus of this proposal is the discovery and development of new catalytic processes originating from metallovinylcarbene [3+n]-cycloaddition reactions and their products. Aim 1 further explores strain-induced ring opening that are made possible through asymmetric catalytic [3+1]-cycloaddition reactions of silyl group protected enoldiazo compounds and. also. initiates investigations of cycloaddition reactions with chiral donor-acceptor cycloalkenes. Nucleophilic strain-induced ring opening of chiral D-A cyclobutenes and azetines have already been demonstrated to be stoichiometric. occur rapidly and with highly selectively at room temperature. and proceed with complete retention of configuration. Aim 2 describes novel approaches to Br??nsted acid catalyzed cycloaddition reactions based on the use of superacid triflimide. In these reactions cycloaddition with product from catalytic enantioselective [3+n]-cycloaddition form intermediates capable of ring expansion to medium ring products. With enoldiazo compounds novel rearrangements open pathways to complex molecular constructions. Aim 3 takes advantage of highly enantioselective catalytic cyclopropanation reactions of enoldiazo compounds to prepare novel D-A cyclopropanes that are capable of cycloaddition. The challenge in this program is to retain the optical purity of the cyclopropane reactant in its catalytic cycloaddition reactions.
 BROADER IMPACTS. The proposed research will expand cycloaddition transformations for the highly selective synthesis of multifunctional organic compounds. New directions are presented for strain-induced ring opening. Br??nsted acid catalyzed cycloaddition reactions. and chiral D-A cyclopropanes for cycloaddition. New methodologies that are optimized for selectivity and yield will be developed. and representative examples of new compounds will be assayed for biological activity. This research offers opportunities for the education and training of postdoctoral students who are preparing for careers in the chemical sciences. Undergraduate students are integrated into the research program with a strong mentoring program to prepare them for their intended careers. UTSA is a minority-rich institution that is seeking to be a prominent center for the education of underrepresented. especially Hispanic. minorities. and this research program will attract and engage these students. The benefits of asymmetric catalysis. metal carbene transformations. and the preparation and reactions of diazo compounds. will continue to be brought to the scientific community through the Metal Carbene Consortium whose efforts are focused on outstanding problems in metal carbene and nitrene chemistry. 

Collaborative Project
Basic Research