​According to Mayr, polar organic synthesis can be rationalized by a simple empirical relationship linking bimolecular rate constants to as few as three reactivity parameters. Here, we propose an extension to Mayr’s reactivity method that is rooted in uncertainty quantification and transforms the reactivity parameters into probability distributions. Through uncertainty propagation, these distributions can be transformed into uncertainty estimates for bimolecular rate constants. Chemists can exploit these virtual error bars to enhance synthesis planning and to decrease the ambiguity of conclusions drawn from experimental data. We demonstrate the above at the example of the reference data set released by Mayr and co-workers [J. Am. Chem. Soc. 2001, 123, 9500; J. Am. Chem. Soc. 2012, 134, 13902]. As by-product of the new approach, we obtain revised reactivity parameters for 36 π-nucleophiles and 32 benzhydrylium ions.

According to Mayr, polar organic synthesis can be rationalized by a simple empirical relationship linking bimolecular rate constants to as few as three reactivity parameters. Here, we propose an extension to Mayr's reactivity method that is rooted in uncertainty quantification and transforms the reactivity parameters into probability distributions. Through uncertainty propagation, these distributions can be transformed into uncertainty estimates for bimolecular rate constants. Chemists can exploit these virtual error bars to enhance synthesis planning and to decrease the ambiguity of conclusions drawn from experimental data. We demonstrate the above at the example of the reference data set released by Mayr and co‐workers [J. Am. Chem. Soc. 2001, 123, 9500; J. Am. Chem. Soc. 2012, 134, 13902]. As by‐product of the new approach, we obtain revised reactivity parameters for 36 π‐nucleophiles and 32 benzhydrylium ions.

This manuscript reports the synthesis and structure of an unprecedented sulfonium salt, 5-(trifluorovinyl)dibenzothiophenium triflate, and its use as a versatile reagent for the introduction of the bioisosteric 1,1,2trifluoroethylene linker in drug-like structures. The protocol developed consists of the reaction of this compound with alcohols and phenols to deliver a complete set of 1,2,2trifluoro-2-(alkoxy-/aryloxy)ethyl sulfonium salts, which have been purified by column chromatography and fully characterized. Subsequent single electron reduction under mild photochemical conditions efficiently affords the corresponding fluoroalkyl radicals that are trapped either intra-or intermolecularly through their reaction with (hetero)arenes. Theoretical calculations are used to evaluate the conformational consequences derived from the presence of the CF 2 À CHF tether.

​According to Mayr, polar organic synthesis can be rationalized by a simple empirical relationship linking bimolecular rate constants to as few as three reactivity parameters. Here, we propose an extension to Mayr’s reactivity method that is rooted in uncertainty quantification and transforms the reactivity parameters into probability distributions. Through uncertainty propagation, these distributions can be transformed into uncertainty estimates for bimolecular rate constants. Chemists can exploit these virtual error bars to enhance synthesis planning and to decrease the ambiguity of conclusions drawn from experimental data. We demonstrate the above at the example of the reference data set released by Mayr and co-workers [J. Am. Chem. Soc. 2001, 123, 9500; J. Am. Chem. Soc. 2012, 134, 13902]. As by-product of the new approach, we obtain revised reactivity parameters for 36 π-nucleophiles and 32 benzhydrylium ions.

What is the most significant result of this study?We show that distributions of Mayr-type reactivity parameters improve the assessment of relative reactivity. Instead of trusting binary statements such as "species A is more/less reactive than species B" (cover image, bottom), uncertainty quantification enables chemists to draw more informed conclusions such as "there is a p % chance that A is more/less reactive than B" (cover image, top).What future opportunities do you see (in the light of the results presented in this paper)? Jonny ProppeJohannes Kircher www.tu-braunschweig.de/en/pci/compmatThe front cover artwork is provided by Prof. Ricardo A. Mata from the University of Gçttingen. The image contrasts singlevalued reactivity parameters and distributions thereof. The latter allow chemists to better assess relative reactivity and, therefore, support synthesis planning. Read the full text of the Research Article at 10.1002/cphc.202200061.