Catalytic Synthesis of Arylboronic Esters

DESCRIPTION (provided by applicant): The usefulness of arylboronic acids or esters in organic synthesis, biology and molecular recognition leads to the origin of this proposal. Classical preparations of arylboronic acids use harsh conditions that can only be tolerated by a very limited number of functional groups. In the past five years, the appearance of new technology has opened the door to the preparation of arylboronic esters with a broader functional group tolerance, although current progress is still limited with respect to yield and substrate specificity. We propose to develop a series of transition metal-based catalysts with the intention of screening for one with high efficiency, practical scalability and broad functionality. In Phase I, we will synthesize a series of ligands and the corresponding complexes. Then we will evaluate the catalytic capability of these complexes as catalysts, based on a standard model reaction. Once the best catalyst is selected, the reaction will be optimized based on reagents, solvents, temperature and additives by using a combinatorial approach coupled with Design of Experiments (DOE) software. In Phase Il, we will expand the use of various substrates for the synthesis of arylboronic esters. If necessary, we will modify the best catalysts and optimize the synthetic method. PROPOSED COMMERCIAL APPLICATION: Arylboronic acids and esters are very important chemical intermediates that are used by pharmaceutical and the related industry in large quantities. The classical preparations of arylboronic acids use harsh conditions that can only be tolerated by a very limited amount of functional groups. MediChem proposes a highly efficient catalytic process to synthesize arylboronic esters or acids with practical scalability and a wide range of functionality that may be commercialized for application in academia and industry.