Professor W. Dean Harman of the University of Virginia is supported by the Chemical Synthesis Program in the Division of Chemistry to conduct research that explores the ability of specially designed tungsten complexes, known as dearomatization agents, to coordinate and activate various types of aromatic molecules toward novel chemical transformations. The cornerstone of this approach is the implementation of highly pi-basic transition metal complexes that forms strong back-bonding interactions with the aromatic molecule. The research focuses on three areas: 1) the activation and manipulation of phenols and anilines 2) the activation and manipulation of polyaromatic hydrocarbons and 3) the development of enantio-enriched dearomatization agents that can be used for the synthesis of enantio-enriched organic products derived from aromatic molecules. These new methodologies will be used to generate new organic compounds that will be broad-screened for biological function and medicinal value.
New synthetic methods that can convert ubiquitous aromatic molecules into highly functionalized molecules provide facile routes for the preparation of new synthetic substances not readily available from other methods. In most cases, these are entirely new compounds, and are of interest to the biochemical and medicinal communities as potential leads for the development of new biological probes and medicines. The project is highly interdisciplinary, combining elements of coordination chemistry, organometallics, organic, and medicinal chemistries. As a result, Ph. D. and undergraduate students involved with this research will receive the type of broad education required for them to be successful as modern synthetic chemists.
The production of modern pharmaceuticals utilizes an elaborate array of methods developed over this past century that stitch together relatively simple petroleum-based molecules into more elaborate chemical structures. When a new synthetic process is developed, it opens the door to the creation of new compounds that can be tested for their biological and medicinal value. Aromatics, a broad class of chemicals found in crude oil, often resist these chemical processes as they are endowed with certain properties that cause them to be unusually stable. The goal of this NSF-funded program has been to increase access to this important and abundant class of materials. A new type of molecule has been invented that can clamp to an aromatic molecule, acting like a "molecular vise". These so-called Dearomatization Agents feature tungsten or molybdenum reaction sites, which have been carefully engineered to disrupt the chemical stability of the bound aromatic. Such action dramatically enhances the chemical reactivity of the arrested molecule, allowing access to a broad range of fundamentally new chemical transformations. This new way of utilizing some of nature's most common molecular building blocks will provide new candidates for medicines and biological probes. Dozens of new chemical reactions discovered from this program have provided hundreds of new molecular compositions and many of these materials have been submitted for testing for their potential use as new medicines. Graduate and undergraduate students that have been involved in this research program have been exposed to a research environment that is fully interdisciplinary, working on problems ranging from medicinal applications to synthesis, to novel reaction mechanisms. They have gained experience with sophisticated analytical instruments and computational methods, and techniques for handling air-sensitive compounds. They have become integrated into the scientific community through presentations at professional meetings, writing manuscripts and proposals, and collaborating with other scientists. In addition, graduate students have developed their mentoring and teaching skills by training and collaborating with undergraduate students.
