Chiral Acetal-Based Stereo-Controlled Degradable Polymer Synthesis.

The precise synthesis of chiral polymers remains a significant challenge in polymer chemistry, particularly for applications in advanced biomedical and electronic materials. The development of degradable polymers is important for eco-friendly and advanced materials. Here, we introduce a stereo-controlled degradable polymer via cascade enyne metathesis polymerization and enantioselective acetal synthesis through Pd-catalyzed asymmetric hydroamination. This approach allows for the creation of chiral acetal-based polymers with controlled stereochemistry and degradability, highlighting their potential for use in drug delivery and electronic applications. This concept article reviews the background, development, and potential applications of these stereo-controlled degradable polymers.

Synthesis of Stereocontrolled Degradable Polymer by Living Cascade Enyne Metathesis Polymerization.

A stereocontrolled degradable polymer was synthesized via living cascade enyne metathesis polymerization. Highly stereodefined N,O-acetal-containing enyne monomers were prepared using the Pd-catalyzed hydroamination of alkoxyallenes and ring-closing metathesis. The resulting chiral polymer exhibited a narrow dispersity window. Block copolymers were prepared not only by sequentially adding nondegradable and degradable monomers but also by using enantiomerically different monomers to produce stereocontrolled blocks. Owing to the hydrolyzable N,O-acetal moiety in the backbone structure, the resulting polymer could degrade under acidic conditions generated using various acid concentrations to control the degradation. Additionally, the aza-Diels-Alder reaction modified the polymer without losing the stereochemistry.

Post-synthetic ligand cyclization in metal-organic frameworks through functional group connection with regioisomerism.

A covalent connection between two orthogonal functional groups (-NH2 and -OH) in metal-organic frameworks (MOFs) has been developed. This post-synthetic ligand cyclization (PSLC) was successfully demonstrated to synthesize a benzoxazole-functionalized MOF from a Zr-based UiO-66-2,3-(NH2)(OH) under microwave irradiation. In contrast, the regioisomeric UiO-66-2,5-(NH2)(OH) only produces a non-cyclized formamide-functionalized MOF.

Visible Light Photochemical Reactions for Nucleic Acid-Based Technologies.

The expanding scope of chemical reactions applied to nucleic acids has diversified the design of nucleic acid-based technologies that are essential to medicinal chemistry and chemical biology. Among chemical reactions, visible light photochemical reaction is considered a promising tool that can be used for the manipulations of nucleic acids owing to its advantages, such as mild reaction conditions and ease of the reaction process. Of late, inspired by the development of visible light-absorbing molecules and photocatalysts, visible light-driven photochemical reactions have been used to conduct various molecular manipulations, such as the cleavage or ligation of nucleic acids and other molecules as well as the synthesis of functional molecules. In this review, we describe the recent developments (from 2010) in visible light photochemical reactions involving nucleic acids and their applications in the design of nucleic acid-based technologies including DNA photocleaving, DNA photoligation, nucleic acid sensors, the release of functional molecules, and DNA-encoded libraries.

Stereoretentive Ring-Opening Metathesis Polymerization to Access All-cis Poly(p-phenylenevinylene)s with Living Characteristics.

Poly(p-phenylenevinylene)s (PPVs), a staple of the conductive polymer family, consist of alternating alkene and phenyl groups in conjugation. The physical properties of this organic material are intimately linked to the cis/trans configuration of the alkene groups. While many synthetic methods afford PPVs with all-trans stereochemistry, very few deliver the all-cis congeners. We report herein a synthesis of all-cis PPVs with living characteristics via stereoretentive ring-opening metathesis polymerization (ROMP). Exquisite catalyst control allows for the preparation of homopolymers or diblock copolymers with perfect stereoselectivity, narrow dispersities, and predictable average molar masses. All-cis PPVs can then serve as light-responsive polymers through clean photoisomerization of the stilbenoid units.

Synthesis of unsymmetrical sulfamides and polysulfamides via SuFEx click chemistry.

As hydrogen-bond donors and acceptors, N,N'-disubstituted sulfamides have been used in a range of applications from medicinal chemistry to anion-binding catalysis. However, compared to ureas or thioureas, the utilization of this unique moiety remains marginal, in part because of a lack of general synthetic methods to access unsymmetrical sulfamides. Specifically, polysulfamides are a virtually unknown type of polymer despite their potential utility in non-covalent dynamic networks, an intense area of research in materials science. We report herein a practical and efficient process to prepare unsymmetrical sulfamides via Sulfur(vi)-Fluoride Exchange (SuFEx) click chemistry. This process was then applied to synthesize polysulfamides. Thermal analysis showed that this family of polymers possess high thermal stability and tunable glass transition temperatures. Finally, hydrolysis studies indicated that aromatic polysulfamides could be recycled back to their constituting monomers at the end of their life cycle.

Heterogeneous Removal of Water-Soluble Ruthenium Olefin Metathesis Catalyst from Aqueous Media Via Host-Guest Interaction.

A highly efficient transition metal catalyst removal method is developed. The water-soluble catalyst contains a newly-designed NHC ligand for the catalyst removal via host-guest interactions. The new NHC ligand possesses an adamantyl (guest) tethered linear ethylene glycol units for hydrophobic inclusion into the cavity of a ß-cyclodextrin (ß-CD) host compound. The new NHC ligand was applied to a Ru-based olefin metathesis catalyst. The Ru catalyst demonstrated excellent activity in representative ring-closing metathesis (RCM) and ring-opening metathesis polymerization (ROMP) reactions in aqueous media as well as organic solvent, CH2Cl2. After the reaction was complete, the lingering Ru residue was removed from the aqueous solution with the efficiency of more than 99% (53 ppm of Ru residue) by simple filtration utilizing a host-guest interaction between insoluble silica-grafted ß-CD (host) and the adamantyl moiety (guest) on the catalyst. The new Ru catalyst also demonstrated high removal efficiency via extraction when the reaction is run in organic solvent by partitioning the crude reaction mixture between layers of diethyl ether and water. In this way, the catalyst stays in aqueous layer only. In organic layer, the residual Ru amount was only 0.14 ppm in the RCM reactions of diallyl compounds.

Oligo(ethylene glycol) Length Effect of Water-Soluble Ru-Based Olefin Metathesis Catalysts on Reactivity and Removability.

A study of reaction kinetics and removal efficiency of a family of ruthenium (Ru)-based olefin metathesis catalysts containing ethylene-glycol-oligomer-tethered N-heterocyclic carbene (NHC) ligands has been carried out, with a focus on variation of ethylene glycol oligomer length. The length of ethylene glycol oligomer was precisely defined by sequential addition of repeating units. Due to the dual solubility of ethylene glycol oligomer, the produced catalyst was highly soluble in both aqueous and organic solvents (dichloromethane). In aqueous solution, the polarity increase with longer ethylene glycol oligomers enhanced the reactivity in homogeneous solution. The length of ethylene glycol oligomer did not significantly affect olefin metathesis rate in organic solution. Yet the removal efficiency of catalyst strongly relies on the length of ethylene glycol oligomer. A longer ethylene glycol oligomer demonstrated better catalyst removal efficiency. The tested catalyst removal method was aqueous extraction from organic solution using its higher water solubility property compared to its lower organic solvent (dichloromethane) solubility property. The results obtained from the aqueous extraction catalyst removal method demonstrated similar and/or better removal rates compared to previously reported host-guest catalyst removal methods.

Removable Water-Soluble Olefin Metathesis Catalyst via Host-Guest Interaction.

A highly removable N-heterocyclic carbene ligand for a transition-metal catalyst in aqueous media via host-guest interactions has been developed. Water-soluble adamantyl tethered ethylene glycol in the ligand leads a hydrophobic inclusion into the cavity of ß-cyclodextrin. Ruthenium (Ru) olefin metathesis catalyst with this ligand demonstrated excellent performance in various metathesis reactions in water as well as in CH2Cl2, and removal of residual Ru was performed via filtration utilizing a host-guest interaction and extraction.

Synthesis of the tricyclic core in stemonamine alkaloids via one-pot gold(I)-catalyzed cyclization and schmidt rearrangement: formal synthesis of (±)-stemonamine.

An efficient synthesis of the tricyclic cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus of stemonamine alkaloids is reported. The key reaction utilizes a one-pot gold(I)-catalyzed cyclization and SnCl4-mediated Schmidt rearrangement. Notably, the phosphine ligand had a crucial effect on the gold(I)-catalyzed cyclization. As an application of this new methodology, the formal synthesis of (±)-stemonamine has been accomplished.

Entry to ß-alkoxyacrylates via gold-catalyzed intermolecular coupling of alkynoates and allylic ethers.

The first gold-catalyzed intermolecular coupling of alkynoates and allylic ethers invoking alkoxy addition and [3,3]-sigmatropic rearrangement as the key mechanism has been developed. Remarkably, the reaction showed complete chemoselectivity toward the pathway initiated by the alkoxy addition to alkynes. This unprecedented reactivity led to a new access to diversely substituted ß-alkoxyacrylates in a highly efficient manner.

Formal alkyne aza-prins cyclization: gold(I)-catalyzed cycloisomerization of mixed N,O-acetals generated from homopropargylic amines to highly substituted piperidines.

A new gold(I)-catalyzed cycloisomerization to access highly substituted piperidines has been developed. By combining a conceptually new way of generating iminium ions using cationic gold(I) complexes and an efficient cyclization reaction that can minimize a potentially competing aza-Cope rearrangement, the proposed reaction successfully circumvents a long-standing problem in the classical aza-Prins reaction. Synthetic utility of the catalytic reaction was demonstrated by a synthesis of optically active 2-alkyl-piperidin-4-one.