Continuous-flow methodologies offer promising avenues for sustainable processing due to their precise process control, scalability, and efficient heat and mass transfer. The small dimensions of continuous-flow reactors render them highly suitable for light-assisted reactions, as can be encountered in carbon dioxide hydrogenations. In this study, we present a reactor system emphasizing reproducibility, modularity, and automation, facilitating streamlined screening of conditions and catalysts for these processes. The proposed commercially available photoreactor, in which carbon dioxide hydrogenation was conducted, features narrow channels with a high-surface area catalyst deposition. Meticulous control over temperature, light intensity, pressure, residence time, and reagent stoichiometry yielded the selective formation of carbon monoxide and methane using heterogeneous catalysts, including a novel variant of ruthenium nanoparticles on titania catalyst. All details on the automation are made available, enabling its use by researchers worldwide. Furthermore, we demonstrated the direct utilization of on-demand generated carbon monoxide in the production of fine chemicals via various carbonylative cross-coupling reactions.

Mechanically interlocked molecules (MiMs), such as catenanes and rotaxanes, exhibit unique properties due to the mechanical bond which unites their components. The translational and rotational freedom present in these compounds may be harnessed to create stimuli-responsive MiMs, which find potential application as artificial molecular machines. Mechanically interlocked structures such as lasso peptides have also been found in nature, making MiMs promising albeit elusive targets for drug discovery. Although the first syntheses of MiMs were based on covalent strategies, approaches based on non-covalent interactions rose to prominence thereafter and have remained dominant. Non-covalent strategies are generally short and efficient, but do require particular structural motifs which are difficult to alter. In a covalent approach, MiMs can be more easily modified while the components may have increased rotational and translational freedom. Both approaches have complementary merits and combining the unmatched efficiency of non-covalent approaches with the scope of covalent syntheses may open up vast opportunities. In this review, recent covalently templated syntheses of MiMs are discussed to show their complementarity and anticipate future developments in this field.

After earlier unsuccessful attempts, this work reports the application of covalent templating for the synthesis of mechanically interlocked molecules (MiMs) bearing no supramolecular recognition sites. Two linear strands were covalently connected in a perpendicular fashion by a central ketal linkage. After subsequent attachment of the first strand to a template via temporary benzylic linkages, the second was linked to the template in a backfolding macrocyclization. The resulting pseudo[1]rotaxane structure was successfully converted to a [2]catenane via a second macrocyclization and cleavage of the ketal and temporary linkages.

Despite the advances in the synthesis of mechanically interlocked molecules, a generally applicable approach to interlocked natural products, such as lasso peptides, is yet to be formulated. While amino acid sequences have been introduced into several rotaxanes, the key structural components have always been dictated by the method used for supramolecular preorganization. In this work, we report the use of an ester-functionalized, aromatic δ-amino acid as the central covalent templating unit in the synthesis of both a [2]catenane and a [2]rotaxane from the same multimacrocyclic intermediate. This represents a key step toward future synthetic peptide-based interlocked products.

An Expedient Approach to Pyrazolo [3,4-b]pyridine-

Incorporation of 2,5-dihydroxyterephthalate as a covalent scaffold in the axis of a 30-membered all-carbon macrocycle provides access to a modular series of rotaxanes. Installment of tethered alkynes or azides onto the terephthalic phenolic hydroxyl functionalities, which are situated at opposite sides of the macrocycle, gives versatile prerotaxane building blocks. The corresponding [2]rotaxanes are obtained by introduction of bulky stoppering ("capping") units at the tethers and subsequent cleavage of the covalent ring/thread ester linkages. Extension of this strategy via coupling of two prerotaxanes bearing complementary linker functionalities (i.e., azide and alkyne) and follow-up attachment of stopper groups provide efficient access to [n]rotaxanes. The applicability and modular nature of this novel approach were demonstrated by the synthesis of a series of [2]-, [3]-, and [4]rotaxanes. Furthermore, it is shown that the prerotaxanes allow late-stage functionalization of the ring fragment introducing further structural diversity.