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![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Spotlight on Mechanosterics: A Bulky Macrocycle Promotes Functional Group Reactivity in a [2]Rotaxane
Thomas Pickl1, Claire Stark1, Diego Briganti1,2
1Catalysis Research Center (CRC) & TUM School of Natural Sciences, Department of Chemistry, Technical University of Munich, Ernst-Otto-Fischer Str. 1, 85747 Garching, Germany.
Abstract:
Macrocycles typically hinder the reactivity of adjacent functional groups in mechanically interlocked molecules due to steric shielding. Herein, we report a [2]rotaxane in which a bulky macrocycle in fact accelerates deprotection of a Fmoc-derived stopper by 36-fold compared to a non-interlocked control. We rationalize this by a preorganization of the macrocycle and the stopper, exposing its reactive site for base abstraction. This is evidenced by extensive NMR, SC-XRD, and DFT studies, revealing highly directional CH-π interactions and hydrogen bonding between the interlocked components. Our findings highlight and structurally rationalize how entanglement can instead promote reactivity through precise spatial control. This concept paves the way for designing molecular machines with functional, reactivity-enhancing components.
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