Apr 25, 2024: Alison Wendlandt (MIT)
“Emergent selectivity in complex stereoarrays” Stereochemical editing has recently become a promising strategy for the synthesis of complex molecules. By enabling surgical alterations at a late synthetic stage, readily accessible substrates can be btransformed into rare and valuable products. However, because many products contain stereoarrays of chemically similar groups, achieving precise control of site- and stereoselectivity is difficult. Typically, this challenge is addressed by reducing the kinetic complexity of the system: by using protecting groups to suppress reactivity at other sites (substrate control) or by using catalysts with tailored shapes to drive selectivity at the editing site (catalyst control). This talk proposes “network control,” a contrasting paradigm that exploits hidden interactions between rate constants to greatly amplify modest intrinsic biases and enable precise multi-site editing. When network complexity is treated as a scale parameter, the amplification effect can be viewed as a mesoscale phenomenon that emerges between the limiting regimes of kinetic control in simple chemical systems and metabolic regulation in complex biological systems. The concept of embracing kinetic complexity to engineer photochemically-driven selectivity landscapes should serve as a general framework for the design of next-generation stereochemical editing systems.