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Abstract Not long ago, the occurrence of quantum mechanical tunneling (QMT) chemistry involving atoms heavier than hydrogen was considered unreasonable. Contributing to the shift of this paradigm, we present here the discovery of a new and distinct heavy‐atom QMT reaction. Triplet syn‐2‐formyl‐3‐fluorophenylnitrene, generated in argon matrices by UV‐irradiation of an azide precursor, was found to spontaneously cyclize to singlet 4‐fluoro‐2,1‐benzisoxazole. Monitoring the transformation by IR spectroscopy, temperature‐independent rate constants (k≈1.4×10−3 s−1; half‐life of ≈8 min) were measured from 10 to 20 K. Computational estimated rate constants are in fair agreement with experimental values, providing evidence for a mechanism involving heavy‐atom QMT through crossing triplet to singlet potential energy surfaces. Moreover, the heavy‐atom QMT takes place with considerable displacement of the oxygen atom, which establishes a new limit for the heavier atom involved in a QMT reaction in cryogenic matrices.
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This content will become publicly available on September 12, 2026
Influence of Heavy-Atom Tunneling on Pericyclic Reactions in Biosynthesis: A Computational Study
Understanding the kinetics of reactions in biosynthetic pathways requires accounting for the contribution of quantum mechanical tunneling to the rates. Whereas hydrogen tunneling in biology is well established, the extent of heavy-atom tunneling in biochemical reactions has been very little studied. We report computational results (M06-2X/cc-pVDZ) on rate constants for electrocyclic ring closures and [3,3] sigmatropic shifts––processes dominated by heavy-atom motions––that are proposed steps in the biosynthesis of four representative natural products. Using direct dynamics, and canonical variational transition state theory with and without the small curvature tunneling approximation, predicted rate constants suggest that heavy-atom tunneling contributes 21% to the electrocyclization step leading to (+)-occidentalol (3), and 28% to the Cope rearrangement leading to a close analogue of dictyoxepin (4), at 298 K. Key structural factors that lead to faster rates at a given temperature and higher tunneling percentages include tethers between the carbons forming a new sigma bond and the release of ring strain from opening of a small ring. Computed 12C/13C kinetic isotope effects for cyclization to 3 provide a possible experimental test of the predictions.
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- PAR ID:
- 10637266
- Publisher / Repository:
- American Chemical Society, Journal of Organic Chemistry
- Date Published:
- Journal Name:
- The Journal of Organic Chemistry
- Volume:
- 90
- Issue:
- 36
- ISSN:
- 0022-3263
- Page Range / eLocation ID:
- 12638 to 12647
- Subject(s) / Keyword(s):
- tunneling computations biosynthesis pericyclic reactions
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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