Controlled Synthesis of Bioderived Poly(limonene carbonate)-Oligolysine Hybrid Macromolecules.

A straightforward and stepwise functionalization of poly(limonene carbonate) (PLC) was achieved through the use of thiol-ene click chemistry introducing primary amine groups. These amines are initiating points for -carboxy anhydride (NCA) ring-opening polymerization (ROP) reactions, allowing us to modify the PLC backbone with oligolysine fragments, thereby creating a polymer brush type macromolecule. These newly prepared biohybrid structures show a clear hydrophilic behavior as evident from their physical behavior and contact angle measurements.

Cu-Catalyzed Asymmetric Synthesis of γ-Amino Alcohols Featuring Tertiary Carbon Stereocenters.

Alkyne-functionalized oxetanes are presented as versatile substrates that in combination with amine reagents can be transformed into structurally diverse, chiral γ-amino alcohols featuring a tetrasubstituted tertiary stereocenter under Cu catalysis. Control experiments demonstrate the privileged nature of these oxetane precursors in terms of yield and asymmetric induction levels in the developed protocol, and postsynthetic modifications offer an easy way to access more advanced synthons.

Addressing Reproducibility Challenges in High-Throughput Photochemistry.

Light-mediated reactions have emerged as an indispensable tool in organic synthesis and drug discovery, enabling novel transformations and providing access to previously unexplored chemical space. Despite their widespread application in both academic and industrial research, the utilization of light as an energy source still encounters challenges regarding reproducibility and data robustness. Herein we present a comprehensive head-to-head comparison of commercially available batch photoreactors, alongside the introduction of the use of batch and flow photoreactors in parallel synthesis.

Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters.

An Expedient Radical Approach for the Decarboxylative Synthesis of Stereodefined All-Carbon Tetrasubstituted Olefins.

We report a user-friendly approach for the decarboxylative formation of stereodefined and complex tri- and tetra-substituted olefins from vinyl cyclic carbonates and amines as radical precursors. The protocol relies on easy photo-initiated α-amino-radical formation followed by addition onto the double bond of the substrate resulting in a sequence involving carbonate ring-opening, double bond relay, CO extrusion and finally O-protonation. The developed protocol is efficient for both mismatched and matched polarity substrate combinations, and the scope of elaborate stereodefined olefins that can be forged including drug-functionalized derivatives is wide, diverse and further extendable to other types of heterocyclic and radical precursors.

Low-Risk Staphylococcus aureus Bacteremia Patients Do Not Require Routine Diagnostic Imaging: A Multicenter, Retrospective, Cohort Study.

Background: Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes.

Methods: We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence.

The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa.

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with and rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm.

Vinyl and Alkynyl Substituted Heterocycles as Privileged Scaffolds in Transition Metal Promoted Stereoselective Synthesis.

ConspectusBiologically active compounds and pharmaceutically relevant intermediates often feature sterically congested stereogenic centers, in particular, carbon stereocenters that are either tertiary tetrasubstituted ones or quaternary in nature. Synthons that comprise such bulky and often structurally complex core units are of high synthetic value and represent important incentives for communities connected to drug discovery and development. Streamlined approaches that give access to a diverse set of compounds incorporating acyclic bulky stereocenters are relatively limited, though vital.

Catalytic Domino Three-Component Synthesis of Functionalized Heterocycles from Carbon Dioxide.

A catalytic domino, three-component reaction has been developed for the transformation of carbon dioxide into functionalized six-membered cyclic carbonates. The catalytic process combines an initial carboxylative cyclization of β-epoxy alcohols followed by an oxa-Michael reaction affording an unparalleled scope of heterocyclic structures. The wide range of functional groups, including free-alcohols, empowers the access to a range of products including C-oxo-based bicyclic heterocycles.

Bicyclic Guanidine Promoted Mechanistically Divergent Depolymerization and Recycling of a Biobased Polycarbonate.

We here report the organocatalytic and temperature-controlled depolymerization of biobased poly(limonene carbonate) providing access to its trans-configured cyclic carbonate as the major product. The base TBD (1,5,7-triazabicyclo[4.4.

Ni-Catalyzed Regio- and Enantioselective Homoallylic Coupling: Synthesis of Chiral Branched 1,5-Dienes Featuring a Quaternary Stereogenic Center and Mechanistic Analysis.

Asymmetric synthesis of small molecules comprising quaternary stereogenic carbon centers represents a challenging objective. Here regio- and enantioselective synthesis of chiral 1,5-dienes featuring quaternary stereocenters is reported via nickel-promoted by reductive homoallylic coupling. The developed methodology features an atypical preference for the formation of unusual branched regioisomers (rr >20 : 1) in a sterically challenging allylic substitution event and furnishes the products with enantiomeric ratios of up to 98 : 2 and with high chemo- and E-selectivity.

Synthesis of Biorenewable Terpene Monomers Using Enzymatic Epoxidation under Heterogeneous Batch and Continuous Flow Conditions.

A commercially available from immobilized onto a macroporous support (Novozym 435) has been employed in the presence of HO as a benign oxidant for the epoxidation of various biorenewable terpenes. This epoxidation protocol was explored under both heterogeneous batch and continuous flow conditions. The catalyst recyclability was also investigated demonstrating good activity throughout 10 cycles under batch conditions, while the same catalyst system could also be productively used under continuous flow operation for more than 30 h.

Comprehensive Mechanistic Scenario for the Cu-Mediated Asymmetric Propargylic Sulfonylation Forging Tertiary Carbon Stereocenters.

Metal-catalyzed propargylic transformations represent a powerful tool in organic synthesis to achieve new carbon-carbon and carbon-heteroatom bonds. However, detailed knowledge about the mechanistic intricacies related to the asymmetric formation of propargylic products featuring challenging heteroatom-substituted tertiary stereocenters is scarce and therefore provides an inspiring challenge. Here, we present a meticulous mechanistic analysis of a propargylic sulfonylation reaction promoted by a chiral Cu catalyst through a combination of experimental techniques and computational studies.

Silver-Mediated Cascade Synthesis of Functionalized 1,4-Dihydro-2H-benzo-1,3-oxazin-2-ones from Carbon Dioxide.

A conceptually novel catalytic domino approach is presented for the synthesis of highly functional 1,4-dihydro-2H-1,3-benzoxazine-2-one derivatives. Key to the chemoselectivity is a proper design of the precursor to override thermodynamically favored parasitic cyclization processes and empower the formation of the desired product through Thorpe-Ingold effects. The synthetic diversity of these CO -based heterocycles is further demonstrated, and the isolation of a reaction intermediate supports an unusual ring-expansion sequence from an α-alkylidene, five-membered cyclic carbonate to a six-membered cyclic carbamate by N-induced isomerization.

Renewable Beta-Elemene Based Cyclic Carbonates for the Preparation of Oligo(hydroxyurethane)s.

Conversion of β-elemene into new β-elemene dicarbonates through epoxidation and halide salt-catalyzed CO cycloaddition reactions is reported. Step-growth polyaddition of this dicarbonate to five different, commercial diamines was investigated under neat conditions at 150 °C yielding non-isocyanate-based low molecular weight oligo(hydroxyurethane)s with 1.3≤M ≤6.

Simple Halogen-Free, Biobased Organic Salts Convert Glycidol to Glycerol Carbonate under Atmospheric CO Pressure.

Glycerol carbonate (GC) has emerged as an attractive synthetic target due to various promising technological applications. Among several viable strategies to produce GC from CO and glycerol and its derivatives, the cycloaddition of CO to glycidol represents an atom-economic an efficient strategy that can proceed via a halide-free manifold through a proton-shuttling mechanism. Here, it was shown that the synthesis of GC can be promoted by bio-based and readily available organic salts leading to quantitative GC formation under atmospheric CO pressure and moderate temperatures.

Decoding Key Transient Inter-Catalyst Interactions in a Reductive Metallaphotoredox-Catalyzed Allylation Reaction.

Metallaphotoredox chemistry has recently witnessed a surge in interest within the field of synthetic organic chemistry through the use of abundant first-row transition metals combined with suitable photocatalysts. The intricate details arising from the combination of two (or more) catalytic components during the reaction and especially the inter-catalyst interactions remain poorly understood. As a representative example of a catalytic process featuring such intricacies, we here present a meticulous study of the mechanism of a cobalt-organophotoredox catalyzed allylation of aldehydes.

Catalyst Engineering Empowers the Creation of Biomass-Derived Polyesters and Polycarbonates.

The introduction of circular principles in chemical manufacturing will drastically change the way everyday plastics are produced, thereby affecting several aspects of the respective value chains in terms of raw feedstock, recyclability, and cost. The ultimate aim is to ensure a paradigm shift toward plastic-based (consumer) materials that overall can offer a more attractive and sustainable carbon footprint, which is an important requisite from a societal, political, and eventually economical point of view. To realize this important milestone, it is vitally important to control the polymerization processes associated with the creation of novel sustainable materials.

A Novel Catalytic Route to Polymerizable Bicyclic Cyclic Carbonate Monomers from Carbon Dioxide.

A new catalytic route has been developed for the coupling of epoxides and CO affording polymerizable six-membered bicyclic carbonates. Cyclic epoxides equipped with a β-positioned OH group can be transformed into structurally diverse bicyclic cyclic carbonates in good yields and with high selectivity. Key to the chemo-selectivity is the difference between the reactivity of syn- and anti-configured epoxy alcohols, with the latter leading to six-membered ring carbonate formation in the presence of a binary Al aminotriphenolate complex/DIPEA catalyst.

Catalytic Ring-Opening Copolymerization of Fatty Acid Epoxides: Access to Functional Biopolyesters.

Fatty acid epoxies serve as valuable starting materials for the development of bio-based polyesters. Here we present a new and efficient catalytic process that allows for the copolymerization of fatty acid-based epoxides and various cyclic anhydrides under attractive process conditions affording functional polyesters. The degree of functionalization and the nature of the polymer backbone can be modulated via monomer design.

Novel Biobased Epoxy Thermosets and Coatings from Poly(limonene carbonate) Oxide and Synthetic Hardeners.

In the area of coating development, it is extremely difficult to find a substitute for bisphenol A diglycidyl ether (DGEBA), the classical petroleum-based raw material used for the formulation of epoxy thermosets. This epoxy resin offers fast curing reaction with several hardeners and the best thermal and chemical resistance properties for applications in coatings and adhesive technologies. In this work, a new biobased epoxy, derived from poly(limonene carbonate) oxide (PLCO), was combined with polyetheramine and polyamineamide curing agents, offering a spectrum of thermal and mechanical properties, superior to DGEBA-based thermosets.

A Biosourced Epoxy Resin for Adhesive Thermoset Applications.

Biobased epoxy-derived raw materials will be essential for future coating and adhesive designs in industry. Here, a facile approach is reported towards the incorporation of limonene into an epoxy-functionalized polycarbonate and its crosslinking with a polyamine curing agent to obtain a thermoset material. For the first time, a solvent-borne adhesive with excellent film-forming, mechanical and adhesion strength properties is described.

Biobased Terpene Derivatives: Stiff and Biocompatible Compounds to Tune Biodegradability and Properties of Poly(butylene succinate).

Different copolymers incorporating terpene oxide units (e.g., limonene oxide) have been evaluated considering thermal properties, degradability, and biocompatibility.

Ni-Catalyzed Decarboxylative Silylation of Alkynyl Carbonates: Access to Chiral Allenes via Enantiospecific Conversions.

A Ni-mediated decarboxylative silylation of alkynyl cyclic carbonates used as versatile propargylic surrogates is reported affording a wide range of highly substituted 2,3- and 3,4-allenol products in good yields. The formal cross-coupling between a tentative intermediate Ni(allenyl) and the silyl reagent was further extended to enantiospecific conversions providing access to chiral allene synthons. This protocol marks the first Ni-catalyzed propargylic silylation proceeding through an S2' manifold.

Pd-catalyzed stereoselective tandem ring-opening amination/cyclization of vinyl γ-lactones: access to caprolactam diversity.

A stereoselective amination/cyclization cascade process has been developed that allows for the preparation of a series of unsaturated and substituted caprolactam derivatives in good yields. This conceptually novel protocol takes advantage of the easy access and modular character of vinyl γ-lactones that can be prepared from simple precursors. Activation of the lactone substrate in the presence of a suitable Pd precursor and newly developed phosphoramidite ligand offers a stereocontrolled ring-opening/allylic amination manifold under ambient conditions.