Applications of automation to reaction optimization and library synthesis

Chapter 1 is a background on Combinatorial Chemistry and the early techniques for generating of diversity. These combinatorial methods evolved into parallel synthesis, as automated techniques became available.; Chapter 2 provides details on the basis for which the automated facility was built and how it was implemented for a wide array of applications including reaction optimization and library synthesis. Unit operations have been the driving force in this design. The use of robotic workstations capable of performing common tasks such as liquid transfers allow the robotics lab to be used in a wide variety of applications.; Chapter 3 describes the results generated from using the automated facility to optimize catalytic reactions. An epoxidation method using methylrhenium trioxide, pyridine, and aqueous hydrogen peroxide was studied and conditions were optimized for terminal, cis-, and trans-substituted olefins. This screening process was accomplished through varying the pyridine additive, the catalyst, and the oxidant and performed in a completely automated fashion. An analytical technique for screening the aminohydroxylation of cinnamamides is reported through the use of mass spectrometry. This method in conjunction with robotics allows for the accelerated screening of this reaction.; Chapter 4 illustrates an approach for process driven library synthesis. Three diepoxde cores are opened with amines and methods for using this efficient ring-opening reaction was developed for generating diversity. These bis-electrophiles were used to generate three libraries totaling approximately 4500 compounds were made in mixtures of 10.