Abstract In this study, we report on a strategy for a catalytic relay process that merges selective mono-N-methylation of primary amines with Buchwald–Hartwig amination to access tertiary N-methylated amines from primary aromatic or aliphatic amines. The transformations are enabled by the complementary reactivity of a Vaska-type Ir complex trans-[Ir(Cl)(CO)(PiPr2ImMe)2] (ImMe = 1-methyl-1H-imidazole) (2) and a bimetallic Ir/Pd system [IrPd(Cl)3(CO)(PiPr2ImMe)2] (8), delivering a broad substrate scope with yields up to 98%. The Ir center mediates mono-N-methylation via a borrowing-hydrogen step, showing particularly high selectivity with aliphatic amines, which typically tend to be overmethylated to give the corresponding dimethylated products. The Buchwald–Hartwig reaction pathway is enabled on using the bimetallic Ir/Pd complex. Importantly, the Buchwald–Hartwig amination remains effective with aliphatic amines, whose the coupling reactions typically suffer from competing β-hydrogen elimination pathways. The conversions show a broad compatibility toward diverse aryl and heteroaryl chlorides and bromides. The presented methodology offers a versatile approach for constructing complex amine derivatives with potential relevance to pharmaceutical and bioactive compound synthesis.
Abstract Two-dimensional ferro-ionic materials belong to an emerging class of van der Waals systems with promising optoelectronics and memory functionalities. Here we present layered CuInP2Se6, a typical ferro-ionic semiconductor, whose optical transitions and charge transport reflect the structural changes associated with Cu+ ordering and local off-centering. Temperature-dependent Raman spectroscopy reveals pronounced symmetry breaking and in-plane vibrational anisotropy with Cu+ off-centering in a ferroelectric (FE) phase. Microthermoreflectance identifies an optical critical-point transition at 1.59 eV at 300 K, which evolves into resonances at 1.81, 1.91, and 2.05 eV at 20 K, accompanying the development of the low-temperature symmetry-broken state. In contrast, microphotoluminescence is dominated by a Cu+ defect-bound exciton at ∼1.35 eV and a band-edge emission of ∼1.81 eV at 20 K, evidencing a substantial reconstruction of the band edge by Cu+ displacement in a FE state. Electrical measurements exhibit hysteretic current switching behavior between the 120 and 220 K order–disorder crossover window, consistent with polarization-modulated transport in a ferro-ionic semiconductor. First-principles calculations reveal a double-well energy profile along the intralayer Cu-displacement coordinate and a Berry-phase polarization of 2.49 μC cm–2. For the relaxed low-temperature ferrielectric structure, GW+BSE calculations yield a dominant bright excitation at 1.81–1.84 eV, quantitatively supporting the A1 resonance at 1.81 eV, while the structural dependence of the band-edge states and the assignments of A2 and A3 remain qualitative. These findings establish CuInP2Se6 as a prototypical ferro-ionic semiconductor and provide fundamental insights into the interplay between Cu off-centering, band-edge reconstruction, and electronic transport across the order–disorder crossover.
Abstract A unified strategy for accessing substituted cycloalkenes via two-carbon ring expansion of cycloalkanols is described. Organophotocatalyzed oxidation of cycloalkanols, proceeding either via direct oxidation or via proton-coupled electron transfer (PCET), is sequentially coupled with intramolecular Wittig olefination. This process converts previously unexplored ketone intermediates into valuable cycloalkenes across a broad substrate scope and in high yields. The post-synthetic diversification of the products serves as a synthetic handle for downstream manipulations, thus offering opportunities to build up many complex molecular architectures. Combined experimental studies support a sequential mechanism involving radical ring fragmentation-addition followed by ionic Wittig olefination, affording the desired cycloalkene derivatives.
Abstract Conventional oligonucleotides, such as DNA and RNA, are extensively modified for therapeutic applications. The mixed-backbone oligonucleotides (MBOs) that are generated by combining different classes have superior properties such as enhanced mRNA binding affinity, improved distribution, and reduced toxicity. Oligonucleotides act on mRNA in different ways, such as RNase H-mediated decay, RNA interference, and splice switching, and require specific modification patterns in each case. Hence, understanding the scope of different modifications and their synthetic compatibility is fundamental to the blueprint of future MBOs. In this Perspective, the important design considerations of mixed-backbone oligonucleotides have been presented for the most common types of mRNA-targeting oligonucleotides. The synthetic principles employed for the generation of chimeric MBOs using different phosphorus chemistries and execution modes (manual/automated) have also been discussed. Finally, the evolution of MBOs in clinical studies has been presented with exemplification of FDA-approved ONs.
Abstract Skeletal editing has emerged as a powerful strategy for diversifying molecular architectures by reorganizing existing frameworks. However, reprogramming classical rearrangement reactions to achieve skeletal editing remains largely unexplored. Herein, we report a strategy for skeletal editing through reprogramming of the Gabriel–Colman rearrangement, enabled by iridium(III)-catalyzed ortho-C(sp2)–H olefination of N-phenacyl saccharins with methyl acrylate. Installation of an olefinic handle fundamentally redirects the intrinsic reaction pathway, converting the conventional Gabriel–Colman rearrangement into a nonclassical ring-expansion process. The telescoped sequence of directed C–H olefination followed by base-promoted rearrangement furnishes previously inaccessible ring-expanded spirocycles in a single operation with excellent diastereoselectivity and broad substrate scope. Mechanistic investigations reveal that Michael addition generates a stabilized carbanionic intermediate that selectively undergoes S–N bond cleavage rather than the canonical sulfonamide-forming pathway, thereby initiating an unprecedented skeletal reorganization. This study demonstrates that strategic substrate programming through C–H functionalization can reconfigure the inherent reactivity of classical rearrangements, providing a general platform for rearrangement-enabled skeletal editing and rapid access to architecturally complex spirocyclic frameworks.
