Unveiling the reactivity of 2H-(thio)pyran-2-(thi)ones in cycloaddition reactions with strained alkynes through
Wei Huang1, Kangqiao Wen1, Scott T Laughlin1
1Department of Chemistry, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11790, USA. scott.laughlin@stonybrook.edu.
Abstract:
Over the past two decades, click chemistry transformations have revolutionized chemical and biological sciences. Among the different strain-promoted cycloadditions, the inverse electron demand Diels-Alder reaction (IEDDA) has been established as a benchmark reaction. We have theoretically investigated the IEDDA reaction of endo-bicyclo[6.1.0]nonyne (endo-BCN) with 2H-pyran-2-one, 2H-thiopyran-2-one, 2H-pyran-2-thione and 2H-thiopyran-2-thione. These 2H-(thio)pyran-2-(thi)ones have displayed different reactivity towards endo-BCN. Density functional theory (DFT) calculations show, in agreement with experiments, that endo-BCN reacts significantly faster with 2H-thiopyran-2-one compared to other 2H-(thio)pyran-2-(thi)one derivatives because of the lower distortion energy. Experimentally determined second-order rate constants for the reaction of a 2H-pyran-2-thione with different strained derivatives, including a 1-methylcyclopropene derivative and several cycloalkynes (exo-BCN, (1R,8S)-bicyclo[6.1.0]non-4-yne-9,9-diyl)dimethanol, dibenzocycylooctyne and a light activatable silacycloheptyne, were used to validate the computational investigations and shed light on this reaction.
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