Efficient synthesis of branched poly(acrylic acid) derivatives via postpolymerization modification

The utility of pentafluorophenyl esters for the selective introduction of functional units and branch points in well-defined poly(acrylic acid) (PAA) derivatives is demonstrated using a combination of controlled radical polymerization and postpolymerization modification. Reversible addition-fragmentation chain transfer enables the synthesis of well-defined copolymers—poly(pentafluorophenyl acrylate-co-tert-butyl acrylate)—with the active ester repeat units serving as attachment points for reaction with primary amines, specifically tris(2-(t-butoxycarbonyl)ethyl)methyl amine (Behera's amine). Deprotection using trifluoroacetic acid removes both the backbone and side chain t-butyl esters to give a series of branched PAA derivatives containing novel tricarboxylic acid side chains that are well suited to complexation and multidentate interactions. Surprisingly, the active ester homopolymer is shown to have the highest reactivity with Behera's amine when compared to copolymers with lower incorporation of pentafluorophenyl esters, suggesting an intriguing interplay of neighboring group effects and steric interactions. The ability to tune the efficiency of postpolymerization modification gives a library of PAA derivatives.     

Visible-Light Photoswitching by Azobenzazoles

Three visible-light responsive photoswitches are reported, azobis(1-methyl-benzimidazole) ( 1 ), azobis(benzoxazole) ( 2 ) and azobis(benzothiazole) ( 3 ). Photostationary distributions are obtained upon irradiation with visible light comprising approximately 80 % of the thermally unstable isomer, with thermal half-lives up to 8 min and are mostly invariant to solvent. On protonation, compound 1 H⁺ has absorption extending beyond 600 nm, allowing switching with yellow light, and a thermal half-life just under 5 minutes. The two isomers have significantly different pK_a values, offering potential as a pH switch. The absorption spectra of 2 and 3 are insensitive to acid, although changes in the thermal half-life of 3 indicate more basic intermediates that significantly influence the thermal barrier to isomerization. These findings are supported by high-level ab initio calculations, which validate that protonation occurs on the ring nitrogen and that the Z isomer is more basic in all cases.     

Copper Bis(oxazoline)-Catalyzed Enantioselective Alkynylation of Benzopyrylium Ions

The stereocontrolled construction of biologically relevant chromanones and tetrahydroxanthones has been achieved through the addition of alkynes to benzopyrylium trilfates under the influence of copper bis(oxazoline) catalysis. Excellent levels of enantiocontrol (63–98 % ee) are achieved in the addition of a variety of alkynes to an array of chromenones with a hydrogen in the 2-position. Promising levels of enantiocontrol (54–67 % ee) are achieved in the alkynylation of chromenones with esters in the 2-position, generating tertiary ether stereocenters resembling those frequently found in naturally occurring metabolites.     

The Forgotten Pyrazines: Exploring the Dakin–West Reaction

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin–West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α-acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal–organic frameworks.     

Octaboraneyl Complexes of Nickel: Monomers for Redox-Active Coordination Polymers

Herein, we establish the preparation, characterization, and reactivity of a new diphosphine ligand, 1,2-bis(di(3-dicyclohexylboraneyl)propylphosphino)ethane (P₂B^Cy₄), a scaffold that contains four pendant boranes. An entryway into the coordination chemistry of P₂B^Cy₄ is established by using nickel, providing the octaboraneyl complex [Ni(P₂B^Cy₄)₂]—this species contains a boron-rich secondary coordination sphere that reacts readily with Lewis bases. In the case of 4,4′-bipyridine, an air-sensitive coordination polymer is obtained. Characterization of this material by solid-state NMR and EPR spectroscopy reveals the presence of a charge-transfer polymer, which forms as a function of intramolecular Ni→4,4′-bpy electron transfer (ET), providing an array of oxidized nickel sites and reduced 4,4′-bpy radical anion sites. Notably, the related intermolecular reaction between the model fragments [Ni(dnppe)₂] (dnppe=1,2-bis(di-n-propylphosphino)ethane) and a bis(boraneyl)-protected 4,4′-bpy, provides no ET. Overall, the P₂B^Cy₄ fragment provides a unique opportunity for Lewis base activation, in one case allowing for the facile construction of monomers for incorporation into redox-active macromolecules.     

Polyhydrido Copper Nanoclusters with a Hollow Icosahedral Core: [Cu30H18{E2P(OR)2}12] (E=S or Se; R=nPr,iPr or iBu)

Although atomically precise polyhydrido copper nanoclusters are of prime interest for a variety of applications, they have so far remained scarce. Herein, this work describes the synthesis of a dithiophosphate-protected copper(I) hydride-rich nanocluster (NC), [Cu₃₀H₁₈{S₂P(OnPr)₂}₁₂] ( 1_H ), fully characterized by various spectroscopic methods and single-crystal X-ray diffraction. The X-ray structure of 1_H reveals an unprecedented central Cu₁₂ hollow icosahedron. Six faces of this icosahedron are capped by Cu₃ triangles, the whole Cu₃₀ core being wrapped by twelve dithiophosphate ligands and the whole cluster has ideal S₆ symmetry. The locations of the 18 hydrides in 1_H were ascertained by a single-crystal neutron diffraction study. They are composed of three types: capping μ₃-H, interstitial μ₄-H (seesaw) and μ₅-H ligands (square pyramidal), in good agreement with the DFT simulations. The numbers of hydrides and ligand resonances in the ¹H NMR spectrum of 1_H are in line with their coordination environment in the solid state, retaining the S₆ symmetry in solution. Furthermore, two new Se-protected polyhydrido copper nanoclusters, [Cu₃₀H₁₈{Se₂P(OR)₂}₁₂] ( 2_H : R=iPr 3_H : R=iBu) were synthesized from their sulfur relative 1_H via ligand displacement reaction and their X-ray structures feature the exceptional case where both the NC shape and size are fully conserved during the course of ligand exchange. DFT and TD-DFT calculations allow understanding the bonding and optical properties of clusters 1_H – 3_H . In addition, the reaction of 1_H with [Pd(PPh₃)₂Cl₂] in the presence of terminal alkynes led to the formation of new bimetallic Cu−Pd alloy clusters [PdCu₁₄H₂{S₂P(OnPr)₂}₆(C≡CR)₆] ( 4 : R=Ph; 5 : R = C₆H₄F).     

EBC-232 and 323: A Structural Conundrum Necessitating Unification of Five In Silico Prediction and Elucidation Methods

Structurally unique halimanes EBC-232 and EBC-323, isolated from the Australian rainforest plant Croton insularis, proved considerably difficult to elucidate. The two diastereomers, which consist an unusual oxo-6,7-spiro ring system fused to a dihydrofuran, were solved by unification and consultation of five in silico NMR elucidation and prediction methods [i.e., ACDLabs, olefin strain energy (OSE), DP4, DU8+ and TD DFT CD]. Structure elucidation challenges of this nature are prime test case examples for empowering future AI learning in structure elucidation.     

A Buchwald–Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs**

A palladium-catalysed Buchwald–Hartwig amination for lenalidomide-derived aryl bromides was optimised using high throughput experimentation (HTE). The substrate scope of the optimised conditions was evaluated for a range of alkyl- and aryl- amines and functionalised aryl bromides. The methodology allows access to new cereblon-based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields.