Amines are one of the most prevalent functional groups in chemistry. Perhaps even more importantly, amines represent one of the most ubiquitous moieties within the realm of bioactive natural products and life-saving pharmaceuticals. The archetypal geometrical property of amines is their sp³ hybridization with the lone pair of nitrogen occupying the apex of the pyramid. Herein, we present a blueprint for quantifying the properties of extremely sterically hindered alkylamines. These amines reach planarity around the nitrogen atom due to the excessive steric hindrance, which results in a conformational re-modeling of the amine moiety. Crucially, the steric properties of amines are characterized by the %V_Bur index, which we show is a general predictive parameter for evaluating the properties of sterically hindered amines. Computational studies on the acidic nature and the reactivity of organometallic Au and Pd complexes are outlined. Density functional theory calculations permit for predictive catalysis, ordering the mapping of extremely hindered tertiary amines by employing artificial intelligence via machine learning. Overall, the study outlines the correlation between the unusual geometry and the key thermodynamic and kinetic properties of extremely hindered alkylamines. The steric hindrance, as quantified by %V_Bur, is the crucial factor influencing the observed trends and the space required to accommodate sterically hindered tertiary amines.

Poly (vinyl ethers) are compounds with great value in the coating industry due to exhibiting properties such as high viscosity, soft adhesiveness, resistance to saponification and solubility in water and organic solvents. However, the main challenge in this field is the synthesis of vinyl ether monomers that can be synthetized by methodologies such as vinyl transfer, reduction of vinyl phosphate ether, isomerization, hydrogenation of acetylenic ethers, elimination, addition of alcohols to alkyne species etc. Nevertheless, the most successful strategy to access to vinyl ether derivatives is the addition of alcohols to alkynes catalyzed by transition metals such as molybdenum, tungsten, ruthenium, palladium, platinum, gold, silver, iridium and rhodium, where gold-NHC catalysts have shown the best results in vinyl ether synthesis. Recently, the hydrophenoxylation reaction was found to proceed through a digold-assisted process where the species that determine the rate of the reaction are PhO-[Au(IPr)] and alkyne-[Au(IPr)]. Later, the improvement of the hydrophenoxylation reaction by using a mixed combination of Cu-NHC and Au-NHC catalysts was also reported. DFT studies confirmed a cost-effective method for the hydrophenoxylation reaction and located the rate-determining step, which turned out to be quite sensitive to the sterical hindrance due to the NHC ligands.

Non‐biological catalysts following the governing principles of enzymes are attractive systems to disclose unprecedented reactivities. Most of those existing catalysts feature an adaptable molecular recognition site for substrate binding that are prone to undergo conformational selection pathways. Herein, we present a non‐biological catalyst that is able to bind substrates via the induced fit model according to in‐depth computational calculations. The system, which is constituted by an inflexible substrate‐recognition site derived from a zinc‐porphyrin in the second coordination sphere, features destabilization of ground states as well as stabilization of transition states for the relevant iridium‐catalyzed C−H bond borylation of pyridine. In addition, this catalyst appears to be most suited to tightly bind the transition state rather than the substrate. Besides these features, which are reminiscent of the action modes of enzymes, new elementary catalytic steps (i. e. C−B bond formation and catalyst regeneration) have been disclosed owing to the unique distortions encountered in the different intermediates and transition states.

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 substituents that lead to the trans isomer.

We report herein an N‐alkylation reaction of amines with alcohols through a hydrogen autotransfer reaction. Unlike other catalytic systems containing transition metals or additives, potassium tertiary butoxide was found to be a unique and effective catalyst for synthesizing secondary amines. The role of the K⁺ ion and the reaction intermediates were studied under control experiments and by theoretical calculations. The reaction was found to be general and tolerates a series of functional groups, providing a convenient method to synthesize N‐alkylated compounds.