The Development and Analysis of New Organic Reactions in Bulk Solution and in Microdroplets
Shyam Sathyamoorthi, Ph.D.
CBC Faculty Candidate
The first portion of this research presentation concerns the methodological development and mechanistic analysis of new C–H functionalization reactions. Over the past twenty years, the invention of protocols for the site-selective functionalization of sp3 C–H bonds has irrevocably altered the state of organic synthesis. Two such reactions that I will be discussing are the oxidative cyclization of carboxylic acids to lactone products using Cu(OAc)2/K2S2O8 and the C–H bromination of N-methyl sulfamate esters with Rh(oct)4/NaOBr. Mechanistic studies have revealed that the former reaction is an intermolecular oxidation process, initiated by the thermolysis of persulfate into sulfate radical anion intermediates. In contrast, the latter reaction proceeds via an intramolecular C–H abstraction by a transiently formed N-centered radical, allowing for the predictable functionalization of a single C–H bond among the many present in a complex molecule.
The second portion of this presentation discusses advancements in the field of organic microdroplet chemistry. It has been previously demonstrated that reactions in microdroplets generated through electrospray ionization (ESI) are often orders of magnitude faster than their counterparts in bulk solution. Sharpless and co-workers previously studied the [2σ+2σ+2π] cycloaddition of diethyl azodicarboxylate (DEAD) and quadricyclane and reported that the addition of water to the neat reagents caused an acceleration in the reaction rate, giving birth to what has been called “on-water” chemistry. We examined this same reaction in aqueous microdroplets (ca. 5 μm diameter), where the cycloaddition reaction is accelerated even further (by a factor of 102) compared to that of the “on-water” reaction reported previously. Although it is well established that microdroplets provide unique environments for a variety of chemical reactions, the mechanisms underlying this phenomenon are not fully understood. Using the nucleophilic ring-opening of limonene oxide with morpholine as a model reaction, the effects of microdroplet size and speed, electrospray voltage, and solvent on reaction progress were delineated. These variables were all shown to profoundly affect the extent of reaction “in droplet”, which is accelerated by a factor of ~105 relative to the process in bulk.