In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Hisashi Yamamoto of the Department of Chemistry at the University of Chicago will continue his efforts in developing catalysts based on chiral tethered bis(8-quinolinolato) metal complexes (TBOxM) for modern chemical synthesis. This class of complexes provides well defined and rigid configuration and has been shown to be capable of introducing a high level of enantiocontrol in several different reactions. In the next funding period, two specific aims will be explored. The first aim is to study TBOxM for Lewis acid catalysis and the second aim is to study them for redox reaction catalysis. The broader impacts involve training undergraduate and graduate students, broadening participation through the inclusion of researchers on the project, and continuing to build a useful chemical transformation strategy for the society.
Such chemistry will contribute to build the solid base of molecular engineering in the future. Successful development of the methodology will have an impact on any area of activity in which the synthesis of catalyst is needed, such as the pharmaceutical, material, and the biological research activities based on chemistry. In addition to the impact that would derive from adoption of this area of research by the wider community, the project offers an excellent training ground for both graduate and undergraduate students.
In this funding period our research focused on the following areas: 1) the use of tethered bis(8-quinolinolato) (TBOx) catalysts for a variety of reactions including propargylation, alkynylation of aldehydes, and conjugate additions; 2) Copper-catalyzed Claisen-rearrangement reaction; 3) Gold-catalyzed synthesis of 5 and 7-member-rings; 4) the application of supersilyl chemistry for the formal total synthesis of avermectin B1a and Z-selective Peterson olefination of a-silyl super silyl esters with aldehydes. The metal catalysts studied in this project allow an access to a large array of chemical compounds. The TBox-catalyzed propargylation and alkynylation and Cu-catalyzed asymmetric Claisen-rearrangement afforded a variety of important chiral building blocks in organic synthesis. We have found double stereodefferentiation of aldol reaction and HF-induced deprotection/spiroketalization to construct stereodefined spiroketal subunits, utilizing them for the formal total synthesis of avarmectin B1a,a member of the avermectin family,originating from soil bacterium Streptomyces avermilitis. The strong directing ability of super silyl ester enabled stereoselective Peterson olefination to provide an efficient synthetic method for the less explored Z-unsaturated esters. The activity of many biologically active and pharmaceutical compounds is often dependent on the stereochemistry within the molecule. This project enables the stereoselective synthesis of a diverse set of compounds that can have biological activity.
