roject 3. Development of Microfluidic Technologies for Reaction Discovery, Methodology Development, and Library Synthesis. 3.
1 Specific Aims. This project represents a collaborative effort between the CMLD-BU and the laboratory of Professor Klavs Jensen of the Department of Chemical Engineering at MIT. The goal of this collaborative project is the development of microfluidic technologies to enable multidimensional reaction screening, photochemical and microwave-mediated reactions, automated reaction optimization, and chemical synthesis of libraries. Each section will address the development of the appropriate modules to be incorporated into an automated microfluidics platform. 1. Microfluidics-Enabled Photochemistry. This project will focus on the development of microfluidic devices with photochemistry capability for use in an automated platform. The photochemical module will be utilized in two chemical methodology projects 1) a multidimensional reaction screen exploring the chemistry of azirines; and 2) evaluation of the photochemical reactivity of complex scaffolds synthesized in the CMLD-BU. 2. Microwave Synthesis using Automated Microfluidics. This project will focus on the development of a microwave module for our automated microfluidics platform. Microwave-induced heating has been shown to be a powerful tool in organic synthesis and thus an important aspect in expansion of the capabilities of this platform. Microfluidics will also address a number of issues related to microwave synthesis such as scale and uniform heating. The project will also include evaluation of chemical methodologies specifically designed to take advantage of the microwave capability on our platform including tandem condensation/inverse demand Diels-Alder reactions of 1,2-dicarbonyls and amidrazones to afford complex alkaloidal scaffolds. 3. Microfluidics-Enabled Automated Optimization and Library Synthesis. This project focuses on two major items in library synthesis, reaction optimization, and parallel synthesis. We will adapt a reaction optimization algorithm, developed in the Jensen lab, to our automated platform. This system will allow us to automate optimization of reactions under development. Using our automated microfluidics platform we will be uniquely positioned to investigate reaction time, temperature, stoichiometry, and reagent variation. This project will also focus on several aspects of library synthesis which may be enabled by microfluidics including: a) heterogeneous catalysis b) multiple step synthesis c) and "inline" workup.
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