Theoretical Elucidation of the Origins of Substituent and Strain Effects on the Rates of Diels–Alder Reactions of 1,2,4,5-Tetrazines

The Diels–Alder reactions of seven 1,2,4,5-tetrazines with unstrained and strained alkenes and alkynes were studied with quantum mechanical calculations (M06-2X density functional theory) and analyzed with the distortion/interaction model. The higher reactivities of alkenes compared to alkynes in th...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2014-08, Vol.136 (32), p.11483-11493
Main Authors: Liu, Fang, Liang, Yong, Houk, K. N
Format: Article
Language:English
Subjects:
Acetylene - chemistry
Alkenes - chemistry
Alkynes - chemistry
Cycloaddition Reaction
Electrons
Ethylenes - chemistry
Kinetics
Models, Molecular
Molecular Structure
Pyridines - chemistry
Quantum Theory
Software
Thermodynamics
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Summary:The Diels–Alder reactions of seven 1,2,4,5-tetrazines with unstrained and strained alkenes and alkynes were studied with quantum mechanical calculations (M06-2X density functional theory) and analyzed with the distortion/interaction model. The higher reactivities of alkenes compared to alkynes in the Diels–Alder reactions with tetrazines arise from the differences in both interaction and distortion energies. Alkenes have HOMO energies higher than those of alkynes and therefore stronger interaction energies in inverse-electron-demand Diels–Alder reactions with tetrazines. We have also found that the energies to distort alkenes into the Diels–Alder transition-state geometries are smaller than for alkynes in these reactions. The strained dienophiles, trans-cyclooctene and cyclooctyne, are much more reactive than unstrained trans-2-butene and 2-butyne, because they are predistorted toward the Diels–Alder transition structures. The reactivities of substituted tetrazines correlate with the electron-withdrawing abilities of the substituents. Electron-withdrawing groups lower the LUMO+1 of tetrazines, resulting in stronger interactions with the HOMO of dienophiles. Moreover, electron-withdrawing substituents destabilize the tetrazines, and this leads to smaller distortion energies in the Diels–Alder transition states.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja505569a