roject 3. Development of Microfluidic Technologies for Reaction Discovery, MethodologyDevelopment, and Library Synthesis.3.
1 Specific Aims. This project represents a collaborative effort between the CMLD-BU and the laboratory ofProfessor Klavs Jensen of the Department of Chemical Engineering at MIT. The goal of this collaborativeproject is the development of microfluidic technologies to enable multidimensional reaction screening,photochemical and microwave-mediated reactions, automated reaction optimization, and chemical synthesis oflibraries. Each section will address the development of the appropriate modules to be incorporated into anautomated microfluidics platform.1. Microfluidics-Enabled Photochemistry. This project will focus on the development of microfluidic deviceswith photochemistry capability for use in an automated platform. The photochemical module will be utilized intwo 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 amicrowave module for our automated microfluidics platform. Microwave-induced heating has been shown tobe a powerful tool in organic synthesis and thus an important aspect in expansion of the capabilities of thisplatform. Microfluidics will also address a number of issues related to microwave synthesis such as scale anduniform heating. The project will also include evaluation of chemical methodologies specifically designed totake advantage of the microwave capability on our platform including tandem condensation/inverse demandDiels-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 twomajor items in library synthesis, reaction optimization, and parallel synthesis. We will adapt a reactionoptimization algorithm, developed in the Jensen lab, to our automated platform. This system will allow us toautomate optimization of reactions under development. Using our automated microfluidics platform we will beuniquely positioned to investigate reaction time, temperature, stoichiometry, and reagent variation. This projectwill 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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