Developing An Intramolecular Cationic [2 + 2] Cycloaddition

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

Intramolecular reactions represent one of the most important venues in organic synthesis, given their ability to expeditiously bring forth a great deal of structural complexity in a highly regio- and stereoselective manner. With support of this award from the Chemical Synthesis Program of the Division of Chemistry at the National Science Foundation, Professor Richard Hsung's research group at the University of Wisconsin-Madison intends to develop asymmetric intramolecular cationic [2 + 2] cycloadditions using chiral Fe(III) catalysts or chiral Brønsted acids, and to design temporary tethered systems for achieving an equivalent of highly regio- and stereoselective intermolecular cycloaddition. An ultimate goal is to feature the cationic [2 + 2] cycloaddition in a total synthesis of natural product, (-)-bielschowskysin, that possesses anti-cancer and anti-malarial activities. Achieving a cationic [2 + 2] cycloaddition will lead to a bio-inspired strategy for synthesizing cyclobutanes, and will allow Professor Hsung's program to significantly impact an area of cycloaddition chemistry that is under-explored and contribute to the field of asymmetric catalysis in areas of chiral Fe(III) reagents as well as Brønsted acids. Designing and developing new methods that can serve as approaches for rapid assembly of complex structures and efficient strategies for constructing natural occurring substances that possess important biological activities remain as one of important quests in modern organic chemistry. With support of this NSF award, Professor Hsung intends to build a research program based on this premise while focusing on a [2 + 2] cycloaddition manifold en route to cyclobutanes, a four-membered all-carbon containing ring that represents a prevalent motif among medicinally useful entities. In addition, all projects proposed here concern various aspects of basic organic chemistry. Thus, they provide a unique opportunity for teaching undergraduate students to develop useful synthetic methodologies based on fundamental concepts, structural designs, and proposed mechanistic models. By accomplishing these objectives, Professor Hsung's research efforts will continue to broaden the impact of synthetic organic chemistry on training and education.