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Abstract Benzylic and allylic electrophiles are well known to react faster in SN2 reactions than aliphatic electrophiles, but the origins of this enhanced reactivity are still being debated. Galabov, Wu, and Allen recently proposed that electrostatic interactions in the transition state between the nucleophile (Nu) and the sp2carbon (C2) adjacent to the electrophilic carbon (C1) play a key role. To test this secondary electrostatic hypothesis, molecular rotors were designed that form similar through‐space electrostatic interactions with C2 in their bond rotation transition states without forming bonds to C1. This largely eliminates the alternative explanation of stabilizing conjugation effects between C1 and C2 in the transition state. The rotor barriers were strongly correlated with the experimentally measured SN2 free energy. Notably, rotors where C2 was sp2or sp‐hybridized had barriers that were consistently 0.5–2.0 kcal mol−1lower than those for rotors where C2 was sp3‐hybridized. Computational studies of atomic charges were consistent with the formation of stabilizing secondary electrostatic interactions. Further confirmation came from observing the benzylic effect in rotors where the first atom was varied, including oxygen, sulfur, nitrogen, and sp2‐carbon. In summary, these studies provided strong experimental support for the role of secondary electrostatic interactions in the SN2 reaction.
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Transition State Stabilizing Effects of Oxygen and Sulfur Chalcogen Bond Interactions
Abstract Non‐covalent chalcogen bond (ChB) interactions have found utility in many fields, including catalysis, organic semiconductors, and crystal engineering. In this study, the transition stabilizing effects of ChB interactions of oxygen and sulfur were experimentally measured using a series of molecular rotors. The rotors were designed to form ChB interactions in their bond rotation transition states. This enabled the kinetic influences to be assessed by monitoring changes in the rotational barriers. Despite forming weaker ChB interactions, the smaller chalcogens were able to stabilize transition states and had measurable kinetic effects on the rotational barriers. Sulfur stabilized the bond rotation transition state by as much as −7.2 kcal/mol without electron‐withdrawing groups. The key was to design a system where the sulfur ‐hole was aligned with the lone pairs of the chalcogen bond acceptor. Oxygen rotors also could form transition state stabilizing ChB interactions but required electron‐withdrawing groups. For both oxygen and sulfur ChB interactions, a strong correlation was observed between transition state stabilizing abilities and electrostatic potential (ESP) of the chalcogen, providing a useful predictive parameter for the rational design of future ChB systems.
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- PAR ID:
- 10642389
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 30
- Issue:
- 54
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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