Development of Flow Chemistry Techniques: Resolution of Problematic Industrial Process Chemistry Reactions

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Analogues of natural products are known to be an abundant reservoir for medicinally relevant compounds, withmany such molecules being commercialized into therapeutically useful drugs, such as cancer therapies.Historically, considerable effort in the field of organic chemistry has been applied to the development of newsynthetic methods for the construction of these natural products and their respective therapeutically usefulderivatives. Although many synthetic transformations have been developed, new synthetic methods areurgently required to make syntheses shorter, safer, greener and more atom economical. It is the goal of thisresearch project to resolve problematic process chemistry reactions that have been identified by Dalton PharmaServices by creating new flow chemistry-based methods that will be used in the synthesis of activepharmaceutical ingredients (API), which are commonly derivatives of natural products. Specifically, we willdevelop new flow-based synthesis protocols for i) reductions using lithium aluminum hydride (LiAlH4) and ii)reduction of alkynes to alkenes that are suitable for process scale applications. Currently, these types ofreactions are particularly problematic to perform on large scale due to safety and reactivity problems that areinherent to batch chemistry reactions. To solve these issues, we will develop flow chemistry synthetic protocolsthat will replace these current process scale batch methods (vide infra). The field of flow chemistry is poised tohave a transformative effect on the discipline of organic synthesis by avoiding the costly, inefficient methods ofbatch, and replacing them with superior methods that allow for safer, greener and more proficient chemicaltransformations. In its simplest form, flow chemistry replaces conventional fixed-volume batch reaction flaskswith flow microreactors, hence the term "flow" chemistry. This research project plans to utilize the benefits offlow chemistry and develop continuous flow processes that will solve the problems that are inherent whenscaling-up these batch reactions. Overall, resolving the problematic batch reactions that have been identified byDalton Pharma Services, and yield much more cost-effective and safer chemical processes.