Labelling and determination of the energy in reactive intermediates in solution enabled by energy-dependent reaction selectivity

• Published in: Nature chemistry Vol. 10; no. 2; pp. 237 - 241
• Main Authors: Kurouchi, Hiroaki, Singleton, Daniel A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2018; Nature Publishing Group
• Subjects: 639/638/403/934; 639/638/440/950; Analytical Chemistry; Balancing; Biochemistry; Chemistry; Chemistry/Food Science; Cleavage; Energy; Inorganic Chemistry; Intermediates; Isotope effect; Labeling; Organic Chemistry; Physical Chemistry; Selectivity
• ISSN: 1755-4330; 1755-4349; 1755-4349
• DOI: 10.1038/nchem.2907

Any long-lived chemical structure in solution is subject to statistical energy equilibration, so the history of any specific structure does not affect its subsequent reactions. This is not true for very short-lived intermediates because energy equilibration takes time. Here, this idea is applied to achieve the ‘energy labelling’ of a reactive intermediate. The selectivity of the ring-opening α-cleavage reaction of the 1-methylcyclobutoxy radical is found here to vary broadly depending on how the radical was formed. Reactions that provide little excess energy to the intermediate lead to a high selectivity in the subsequent cleavage (measured as a kinetic isotope effect), whereas reactions that provide more excess energy to the intermediate exhibit a lower selectivity. Accounting for the expected excess energy allows the prediction of the observed product ratios and, in turn, the product ratios can be used to determine the energy present in an intermediate. Short-lived intermediates in solution may react before undergoing thermal equilibration. This phenomenon is used here to achieve the ‘energy labelling’ of an alkoxy radical. The intermediate's excess energy varies broadly depending on how it is formed and can be determined from the observed reaction selectivity.