Synlett
DOI: 10.1055/a-1463-9527
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Cooperative Hydrogen Atom Transfer: From Theory to Applications

Padmanabha Venkatesh
1  Rice University Wiess School of Natural Sciences, Chemistry, Houston, United States (Ringgold ID: RIN124473)
,
2  Rice University, Chemistry, Houston, United States (Ringgold ID: RIN3990)
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Hydrogen atom transfer (HAT) is one of the fundamental transformations of organic chemistry, allowing for the interconversion of open and closed shell species through the concerted movement of a proton an electron. While the value of this transformation is well-appreciated in isolation, allowing for homolytic C–H activation via abstractive HAT and radical reduction via donative HAT, cooperative HAT (cHAT) reactions, where two hydrogen atoms are removed or donated to vicinal reaction centers in succession proceeding through radical intermediates, are comparatively unknown outside of the mechanism of desaturase enzymes. This tandem reaction scheme has important ramifications in the thermochemistry of each HAT, with the bond dissociation energy of the C–H bond adjacent to the radical center being significantly lowered compared to that of the parent alkane, allowing for each HAT to be performed by different species. Here we discuss the thermodynamic basis of this bond strength differential in cHAT and demonstrate its use as a design principle in organic chemistry for both dehydrogenative (application 1) and hydrogenative (application 2) reactions. Together, we hope that this overview will highlight the exciting reactivity possible with cHAT and inspire further development using this mechanistic approach.



Publication History

Received: 10 March 2021

Accepted after revision: 24 March 2021

Publication Date:
24 March 2021 (online)

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