Carbodiimides are important crosslinkers in organic synthesis and are used in the isocyanate industry as modifier additives. Therefore, the understanding of their formation is of high importance. In this work, we present a theoretical B3LYP/6-31G(d) and SMD solvent model and experimental investigation of the formation of diphenylcarbodiimide (CDI) from phenyl isocyanate using a phosphorus-based catalyst (MPPO) in ortho-dichlorobenzene (ODCB) solvent. Kinetic experiments were based on the volumetric quantitation of CO2 evolved, at different temperatures between 40 and 80 °C. Based on DFT calculations, we managed to construct a more detailed reaction mechanism compared to previous studies which is supported by experimental results. DFT calculations revealed that the mechanism is composed of two main parts, and the rate determining step of the first part, controlling the CO2 formation, is the first transition state with a 52.9 kJ mol-1 enthalpy barrier. The experimental activation energy was obtained from the Arrhenius plot (ln k vs. 1/T) using the observed second-order kinetics, and the obtained 55.8 ± 2.1 kJ mol-1 was in excellent agreement with the computational one, validating the complete mechanism, giving a better understanding of carbodiimide production from isocyanates.

Borane catalysis has emerged as a powerful technology in epoxide polymerization. Still, the structure-activity correlations for these catalysts are not fully understood to date, especially regarding compounds with nonionic backbones. Thus, in this work, 13 different borane catalysts of this respective type are described and investigated for their epoxide oligomerization and polymerization performance, using propylene oxide (PO), 1-butylene oxide (BO) and allyl glycidyl ether (AGE) as monomers. Structurally, special emphasis is put on catalysts with different linker lengths and linker flexibilities as well as the introduction of more than two borane functionalities. Importantly, this screening is conducted both under typical polymerization conditions as well as under the chain transfer agent (CTA)-rich conditions relevant for large-scale production. It is found that suitable preorganization of the borane groups, such as present in biphenyl derivatives, offers a simple route to high-performing catalysts and quantitative monomer conversion of the investigated epoxides. Furthermore, it is demonstrated that a diborane-catalyzed oligomerization can be kept active over weeks, whereby repeated addition of monomer batches (14 steps) constantly results in full conversion and well-defined oligoethers, underlining the practical potential of this method. The absence of co-initiating counter ions is suggested as an inherent advantage of nonionic catalysts.

The design, synthesis, and initial study of amino-functionalized porphyrins as a new class of bifunctional catalysts for asymmetric organophotocatalysis is described. Two new types of amine-porphyrin hybrids derived from 5,10,15,20-tetraphenylporphyrin (TPPH2), in which a cyclic secondary amine moiety is covalently linked either to a β-pyrrolic position (Type A) or to the p-position of one of the meso phenyl groups (Type B), were prepared by condensation, reductive amination, or amidation reactions from the suitable porphyrins (either formyl or methanamine derivatives) with readily available chiral amines. A preliminary study of the possible use of Type A amine-porphyrin hybrids as asymmetric, bifunctional organophotocatalysts was performed using the chiral, imidazolidinone-catalyzed Diels-Alder cycloaddition between cyclopentadiene 28 and trans-cinnamaldehyde 29 as a benchmark reaction. The yield and the stereochemical outcome of this process, obtained under purely organocatalytic conditions, under dual organophocatalysis, and under bifunctional organophotocatalysis, were compared.

Cyclodextrins (CDs) are cyclic oligosaccharides used in many fields. Grafting polymers onto CDs enables new structures and applications to be obtained. Polylactide (PLA) is a biobased, biocompatible aliphatic polyester that can be grafted onto CDs by -OH-initiated ring-opening polymerization. Using 4-dimethylaminopyridine (DMAP) as an organocatalyst, a quantitative functionalization is reached on native α-, β-, γ- and 2,3-dimethyl- β-cyclodextrins. Narrow molecular weight distributions are obtained with the native CDs (dispersity < 1.1). The DMAP/β-CD combination is used as a case study, and the formation of an inclusion complex (1/1) is shown for the first time in the literature, which is fully characterized by NMR. The inclusion of DMAP into the cavity occurs via the secondary rim of the β-CD and the association constant (Ka) is estimated to be 88.2 M-1. Its use as an initiator for ring-opening polymerization leads to a partial functionalization efficiency, and thus a more hydrophilic β-CD-PLA conjugate than that obtained starting from native β-CD. Polymerization results including also the use of the adamantane/β-CD inclusion complex as an initiator suggest that inclusion of the DMAP catalyst into the CD may not occur during polymerization reactions. Rac-lactide does not form an inclusion complex with β-CD.

Chiral phase-transfer catalysis provides high level of enantiocontrol, however no experimental data showed the interaction of catalysts and substrates. 1 H NMR titration was carried out on Cinchona and Maruoka ammonium bromides vs. nitro, carbonyl, heterocycles, and N-F containing compounds. It was found that neutral organic species and quaternary ammonium salts interacted via an ensemble of catalyst + N-C-H and (sp2 )C-H, specific for each substrate studied. The correspondent BArF salts interacted with carbonyls via a diverse set of + N-C-H and (sp2 )C-H compared to bromides. This data suggests that BArF ammonium salts may display a different enantioselectivity profile. Although not providing quantitative data for the affinity constants, the data reported proofs that chiral ammonium salts coordinate with substrates, prior to transition state, through specific C-H positions in their structures, providing a new rational to rationalize the origin of enantioselectivity in their catalyses.

This work involves a facile synthesis of three (S) -proline-based organocatalysts with C2 symmetry and their effects in enantioselective aldol reaction of acetone with substituted aromatic aldehydes. Moderate enantioselectivities (up to 61% ee) were obtained depending on the nature of the substituents on the aryl ring. Computational calculations at HF/6-31 + G(d) level were employed to underline the enantioselectivity imposed by all the organocatalysts. Higher calculations at B3LYP/6-311 ++ G(d,p) scrf=(solvent=dichloromethane)//B3LYP/6-31 + G(d) levels of theory were also performed for the aldol reaction of acetone with benzaldehyde and 4-nitrobenzaldehyde catalyzed by 1. The computational outcomes were consistent with those produced by experimental results and they were valuable to elucidate the mechanism for the observed stereoselectivity.

Theoretical calculations were performed to investigate the mechanism and enantioselectivity of cinchonine-thiourea-catalyzed intramolecular hetero-Diels-Alder cycloaddition of ethynylphenol derivatives to afford axial chirality naphthalenylpyran products via a vinylidene ortho-quinone methide (VQM) intermediate. The results show that this transformation occurs through a reaction pathway involving the deprotonation of the naphthol moiety by the quinuclidine base, intramolecular proton transfer in ammonium naphthalenolate, and [4+2] cycloaddition. It is found that the axial chirality of the VQM intermediate is generated by the protonation step, which affects the enantioselectivity of the reaction. The enantioselectivity for the generation of the VQM intermediate is controlled by steric repulsion with the cinchonine framework, which provides an R-axial chirality VQM as the major intermediate. Moreover, the enantioselectivity for the axial chirality of the naphthopyran product is controlled by the cycloaddition step, in which an extra hydrogen bond between the naphthalenol and cinchonine moieties leads to a favorable configuration for the generation of the S-axial chirality naphthopyran product. The calculated enantioselectivity and enantiomeric excesses coincide with experimental observations.

The study of hydrogen bonding organocatalysis is rapidly expanding. Much research has been directed at making catalysts more active and selective, with less attention on fundamental design strategies. This study systematically increases steric hindrance at the active site of pH switchable urea organocatalysts. Incorporating strong intramolecular hydrogen bonds from protonated pyridines to oxygen stabilizes the active conformation of these ureas thus reducing the entropic penalty that results from substrate binding. The effect of increasing steric hindrance was studied by single crystal X-ray diffraction and by kinetics experiments of a benchmark reaction.

Three-component Mannich reaction of acetophenone or 4-iodoacetophenone with a variety of substituted anilines and benzaldehyde, catalysed with diethanolammonium chloroacetate, was performed under mild conditions. Mannich bases (MBs), of which five are new, were obtained in good to excellent yields. All compounds were characterized using elemental analysis, NMR and IR. In addition, detailed experimental and simulated UV-Vis spectral characterization of these compounds is presented here for the first time. In vitro antioxidative potential of synthetized MBs was evaluated using 2,2-diphenyl-1-picryl-hydrazyl radical and density functional theory (DFT) thermodynamical study. It was shown that compounds with anisidine moiety express moderate antioxidative activity. Mechanism of the organocatalysed Mannich reaction was thoroughly inspected by means of DFT. The reaction undergoes the hydrogen bonding-assisted mechanism. Moreover, the proposed rate determining step of the overall reaction is water elimination in the process of iminium ion formation. To the extent of our knowledge, this is the first detailed report on the influence of this type of catalyst on the formation of iminium ion, as a crucial intermediate for the whole reaction.

The aldol reaction in the presence of L-proline acting as an organocatalyst is a well-known example of asymmetric synthesis. Many theoretical and experimental studies have been carried out to probe the mechanism of this reaction. In this work, two levels of density functional theory in the gas phase and DMSO were used to elucidate the best pathways for this reaction, with the enamine and enol considered intermediates and L-proline considered either a reactant or a facilitator. The calculations indicated that both intermediates are formed simultaneously in the reaction medium. Interestingly, the formation of the enamine intermediate predominates in DMSO at room temperature, whereas the enol becomes the predominant intermediate upon the addition of water. Graphical Abstract The dual role of L-proline leads to single stereoisomeric aldol product via two completely different pathways.