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The cis – trans isomerization of (thio)amides was studied by DFT calculations to get the model for the higher preference for the cis conformation by guided predictive chemistry, suggesting how to select the alkyl/aryl substituents on the C/N atoms that lead to the trans isomer. Multilinear analysis, together with cross-validation analysis, helped to select the best fitting parameters to achieve the energy barriers of the cis to trans interconversion, as well as the relative stability between both isomers. Double experimental check led to the synthesis of the best trans candidate with sterically demanding t -butyl substituents, confirming the utility of predictive chemistry, bridging organic and computational chemistry. 

The cross-coupling of aryl esters has emerged as a powerful platform for the functionalization of otherwise inert acyl C–O bonds in chemical synthesis and catalysis. Herein, we report a combined experimental and computational study on the acyl Suzuki–Miyaura cross-coupling of aryl esters mediated by well-defined, air- and moisture-stable Pd( ii )–NHC precatalysts [Pd(NHC)(μ-Cl)Cl] 2 . We present a comprehensive evaluation of [Pd(NHC)(μ-Cl)Cl] 2 precatalysts and compare them with the present state-of-the-art [(Pd(NHC)allyl] precatalysts bearing allyl-type throw-away ligands. Most importantly, the study reveals [Pd(NHC)(μ-Cl)Cl] 2 as the most reactive precatalysts discovered to date in this reactivity manifold. The unique synthetic utility of this unconventional O–C(O) cross-coupling is highlighted in the late-stage functionalization of pharmaceuticals and sequential chemoselective cross-coupling, providing access to valuable ketone products by a catalytic mechanism involving Pd insertion into the aryl ester bond. Furthermore, we present a comprehensive study of the catalytic cycle by DFT methods. Considering the clear advantages of [Pd(NHC)(μ-Cl)Cl] 2 precatalysts on several levels, including facile one-pot synthesis, superior atom-economic profile to all other Pd( ii )–NHC catalysts, and versatile reactivity, these should be considered as the ‘first-choice’ catalysts for all routine applications in ester O–C(O) bond activation. 

The Pd–NHC-catalyzed acyl-type Buchwald–Hartwig cross-coupling of amides by N–C(O) cleavage (transamidation) provides a valuable alternative to the classical methods for amide synthesis. Herein, we report a combined experimental and computational study of the Buchwald–Hartwig cross-coupling of amides using well-defined, air- and moisture-stable [Pd(NHC)(allyl)Cl] precatalysts. Most crucially, we present a comprehensive evaluation of a series of distinct Pd( ii )–NHC precatalysts featuring different NHC scaffolds and throw-away ligands for the synthesis of functionalized amides that are not compatible with stoichiometric transition-metal-free transamidation methods. Furthermore, we present evaluation of the catalytic cycle by DFT methods for a series of different Pd( ii )–NHC precatalysts. The viability of accessing NHC-supported acyl-palladium( ii ) amido complexes will have implications for the design and development of cross-coupling methods involving stable amide electrophiles. 

Fullerenes, in particular C 60 , are important molecular entities in many areas, ranging from material science to medicinal chemistry. However, chemical transformations have to be done in order to transform C 60 in added-value compounds with increased applicability. The most common procedure corresponds to the classical Diels–Alder cycloaddition reaction. In this research, a comprehensive study of the electronic activity that takes place in the cycloaddition between C 60 and cyclopentadiene toward the [5,6] and [6,6] reaction pathways is presented. These are competitive reaction mechanisms dominated by σ and π fluctuating activity. To better understand the electronic activity at each stage of the mechanism, the reaction force (RF) and the symmetry-adapted reaction electronic flux (SA-REF, J Γi ( ξ )) have been used to elucidate whether π or σ bonding changes drive the reaction. Since the studied cycloaddition reaction proceeds through a C s symmetry reaction path, two SA-REF emerge: J A′ ( ξ ) and J A′′ ( ξ ). In particular, J A′ ( ξ ) mainly accounts for bond transformations associated with π bonds, while J A′′ ( ξ ) is sensitive toward σ bonding changes. It was found that the [6,6] path is highly favored over the [5,6] with respect to activation energies. This difference is primarily due to the less intensive electronic reordering of the σ electrons in the [6,6] path, as a result of the pyramidalization of carbon atoms in C 60 (sp 2 → sp 3 transition). Interestingly, no substantial differences in the π electronic activity from the reactant complex to the transition state structure were found when comparing the [5,6] and [6,6] paths. Partition of the kinetic energy into its symmetry contributions indicates that when a bond is being weakened/broken (formed/strengthened) non-spontaneous (spontaneous) changes in the electronic activity occur, thus prompting an increase (decrease) of the kinetic energy. Therefore, contraction (expansion) of the electronic density in the vicinity of the bonding change is expected to take place.