Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis.

Public health studies indicate that artificial light is a high-risk factor for metabolic disorders. However, the neural mechanism underlying metabolic modulation by light remains elusive. Here, we found that light can acutely decrease glucose tolerance (GT) in mice by activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) innervating the hypothalamic supraoptic nucleus (SON). Vasopressin neurons in the SON project to the paraventricular nucleus, then to the GABAergic neurons in the solitary tract nucleus, and eventually to brown adipose tissue (BAT). Light activation of this neural circuit directly blocks adaptive thermogenesis in BAT, thereby decreasing GT. In humans, light also modulates GT at the temperature where BAT is active. Thus, our work unveils a retina-SON-BAT axis that mediates the effect of light on glucose metabolism, which may explain the connection between artificial light and metabolic dysregulation, suggesting a potential prevention and treatment strategy for managing glucose metabolic disorders.

Discovery of charge density wave in a kagome lattice antiferromagnet.

A hallmark of strongly correlated quantum materials is the rich phase diagram resulting from competing and intertwined phases with nearly degenerate ground-state energies1,2. A well-known example is the copper oxides, in which a charge density wave (CDW) is ordered well above and strongly coupled to the magnetic order to form spin-charge-separated stripes that compete with superconductivity1,2. Recently, such rich phase diagrams have also been shown in correlated topological materials. In 2D kagome lattice metals consisting of corner-sharing triangles, the geometry of the lattice can produce flat bands with localized electrons3,4, non-trivial topology5-7, chiral magnetic order8,9, superconductivity and CDW order10-15. Although CDW has been found in weakly electron-correlated non-magnetic AV3Sb5 (A = K, Rb, Cs)10-15, it has not yet been observed in correlated magnetic-ordered kagome lattice metals4,16-21. Here we report the discovery of CDW in the antiferromagnetic (AFM) ordered phase of kagome lattice FeGe (refs. 16-19). The CDW in FeGe occurs at wavevectors identical to that of AV3Sb5 (refs. 10-15), enhances the AFM ordered moment and induces an emergent anomalous Hall effect22,23. Our findings suggest that CDW in FeGe arises from the combination of electron-correlations-driven AFM order and van Hove singularities (vHSs)-driven instability possibly associated with a chiral flux phase24-28, in stark contrast to strongly correlated copper oxides1,2 and nickelates29-31, in which the CDW precedes or accompanies the magnetic order.

Dominant activities of fear engram cells in the dorsal dentate gyrus underlie fear generalization in mice.

Over-generalized fear is a maladaptive response to harmless stimuli or situations characteristic of posttraumatic stress disorder (PTSD) and other anxiety disorders. The dorsal dentate gyrus (dDG) contains engram cells that play a crucial role in accurate memory retrieval. However, the coordination mechanism of neuronal subpopulations within the dDG network during fear generalization is not well understood. Here, with the Tet-off system combined with immunostaining and two-photon calcium imaging, we report that dDG fear engram cells labeled in the conditioned context constitutes a significantly higher proportion of dDG neurons activated in a similar context where mice show generalized fear. The activation of these dDG fear engram cells encoding the conditioned context is both sufficient and necessary for inducing fear generalization in the similar context. Activities of mossy cells in the ventral dentate gyrus (vMCs) are significantly suppressed in mice showing fear generalization in a similar context, and activating the vMCs-dDG pathway suppresses generalized but not conditioned fear. Finally, modifying fear memory engrams in the dDG with "safety" signals effectively rescues fear generalization. These findings reveal that the competitive advantage of dDG engram cells underlies fear generalization, which can be rescued by activating the vMCs-dDG pathway or modifying fear memory engrams, and provide novel insights into the dDG network as the neuronal basis of fear generalization.

PerturbDB for unraveling gene functions and regulatory networks.

Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform to help users unveil gene functions using Perturb-Seq datasets. PerturbDB hosts 66 Perturb-Seq datasets, which encompass 4 518 521 single-cell transcriptomes derived from the knockdown of 10 194 genes across 19 different cell lines. All datasets were uniformly processed using the Mixscape algorithm. Genes were clustered by their perturbed transcriptomic phenotypes derived from Perturb-Seq data, resulting in 421 gene clusters, 157 of which were stable across different cellular contexts. Through integrating chemically perturbed transcriptomes with Perturb-Seq data, we identified 552 potential inhibitors targeting 1409 genes, including an mammalian target of rapamycin (mTOR) signaling inhibitor, retinol, which was experimentally verified. Moreover, we developed a 'Cancer' module to facilitate the understanding of the regulatory role of genes in cancer using Perturb-Seq data. An interactive web interface has also been developed, enabling users to visualize, analyze and download all the comprehensive datasets available in PerturbDB. PerturbDB will greatly drive gene functional studies and enhance our understanding of the regulatory roles of genes in diseases such as cancer.

Resistance gene-guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases.

With the significant increase in the availability of microbial genome sequences in recent years, resistance gene-guided genome mining has emerged as a powerful approach for identifying natural products with specific bioactivities. Here, we present the use of this approach to reveal the roseopurpurins as potent inhibitors of cyclin-dependent kinases (CDKs), a class of cell cycle regulators implicated in multiple cancers. We identified a biosynthetic gene cluster (BGC) with a putative resistance gene with homology to human CDK2. Using targeted gene disruption and transcription factor overexpression in Aspergillus uvarum, and heterologous expression of the BGC in Aspergillus nidulans, we demonstrated that roseopurpurin C (1) is produced by this cluster and characterized its biosynthesis. We determined the potency, specificity, and mechanism of action of 1 as well as multiple intermediates and shunt products produced from the BGC. We show that 1 inhibits human CDK2 with a Kiapp of 44 nM, demonstrates selectivity for clinically relevant members of the CDK family, and induces G1 cell cycle arrest in HCT116 cells. Structural analysis of 1 complexed with CDK2 revealed the molecular basis of ATP-competitive inhibition.

GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Evidence for Admixture and Rapid Evolution During Glacial Climate Change in an Alpine Specialist.

The pace of current climate change is expected to be problematic for alpine flora and fauna, as their adaptive capacity may be limited by small population size. Yet, despite substantial genetic drift following post-glacial recolonization of alpine habitats, alpine species are notable for their success surviving in highly heterogeneous environments. Population genomic analyses demonstrating how alpine species have adapted to novel environments with limited genetic diversity remain rare, yet are important in understanding the potential for species to respond to contemporary climate change. In this study, we explored the evolutionary history of alpine ground beetles in the Nebria ingens complex, including the demographic and adaptive changes that followed the last glacier retreat. We first tested alternative models of evolutionary divergence in the species complex. Using millions of genome-wide SNP markers from hundreds of beetles, we found evidence that the N. ingens complex has been formed by past admixture of lineages responding to glacial cycles. Recolonization of alpine sites involved a distributional range shift to higher elevation, which was accompanied by a reduction in suitable habitat and the emergence of complex spatial genetic structure. We tested several possible genetic pathways involved in adaptation to heterogeneous local environments using genome scan and genotype-environment association approaches. From the identified genes, we found enriched functions associated with abiotic stress responses, with strong evidence for adaptation to hypoxia-related pathways. The results demonstrate that despite rapid demographic change, alpine beetles in the N. ingens complex underwent rapid physiological evolution.

Rewiring of uric acid metabolism in the intestine promotes high-altitude hypoxia adaptation in humans.

Adaptation to high-altitude hypoxia is characterized by systemic and organ-specific metabolic changes. This study investigates whether intestinal metabolic rewiring is a contributing factor to hypoxia adaptation. We conducted a longitudinal analysis over 108 days, with seven timepoints, examining fecal metabolomics data from a cohort of 46 healthy male adults traveling from Chongqing (a.s.l. 243 m) to Lhasa (a.s.l. 3658 m) and back. Our findings reveal that short-term hypoxia exposure significantly alters intestinal metabolic pathways, particularly those involving purines, pyrimidines, and amino acids. A notable observation was the significantly reduced level of intestinal uric acid (UA), the end product of purine metabolism, during acclimatization (also called acclimation) and in additional two long-term exposed cohorts (Han Chinese and Tibetans) residing in Shigatse, Xizang (a.s.l. 4700 m), suggesting that low intestinal UA levels facilitate adaptation to high-altitude hypoxia. Integrative analyses with gut metagenomic data showed consistent trends in intestinal UA levels and the abundance of key UA-degrading bacteria, predominantly from the Lachnospiraceae family. The sustained high abundance of these bacteria in the long-term resident cohorts underscores their essential role in maintaining low intestinal UA levels. Collectively, these findings suggest that the rewiring of intestinal UA metabolism, potentially orchestrated by gut bacteria, is crucial for enhancing human resilience and adaptability in extreme environments.

N6-methyladenosine transcriptome-wide profiles of maize kernel development.

Maize (Zea mays L.) kernel development is a complex and dynamic process involving cell division and differentiation, into a variety of cell types. Epigenetic modifications, including DNA methylation, play a pivotal role in regulating this process. N6-methyladenosine modification is a universal and dynamic post-transcriptional epigenetic modification that is involved in the regulation of plant development. However, the role of N6-methyladenosine in maize kernel development remains unknown. In this study, we have constructed transcriptome-wide profiles for maize kernels at various stages of early development. Utilizing a combination of MeRIP-seq and RNA-seq analysis, we identified a total of 11,170, 10,973, 11,094, 11,990, 12,203 and 10,893 N6-methyladenosine peaks in maize kernels at 0, 2, 4, 6, 8, and 12 days after pollination, respectively. These N6-methyladenosine modifications were primarily deposited at the 3'-UTRs and were associated with the conserved motif-UGUACA. Additionally, we found that conserved N6-methyladenosine modification are involved in the regulation of genes that are ubiquitously expressed during kernel development. Further analysis revealed that N6-methyladenosine peak intensity was negatively correlated with the mRNA abundance of these ubiquitously expressed genes. Meanwhile, we employed phylogenetic analysis to predict potential regulatory proteins involved in maize kernels development and identified several that participate in the regulation of N6-methyladenosine modifications. Collectively, our results suggest the existence of a novel post-transcriptional epigenetic modification mechanism involved in the regulation of maize kernels development, thereby providing a novel perspective for maize molecular breeding.

Van der Waals Electrides.

ConspectusElectrides make up a fascinating group of materials with unique physical and chemical properties. In these materials, excess electrons do not behave like normal electrons in metals or form any chemical bonds with atoms. Instead, they "float" freely in the gaps within the material's structure, acting like negatively charged particles called anions (see the graph). Recently, there has been a surge of interest in van der Waals (vdW) electrides or electrenes in two dimensions. A typical example is layered lanthanum bromide (LaBr2), which can be taken as [La3+(Br1-)2]+•(e-). Each excess free electron is trapped within a hexagonal pore, forming dense dots of electron density. These anionic electrons are loosely bound, giving vdW electrides some unique properties such as ferromagnetism, superconductivity, topological features, and Dirac plasmons. The high density of the free electron makes electrides very promising for applications in thermionic emission, organic light-emitting diodes, and high-performance catalysts.In this Account, we first discuss the discovery of numerous vdW electrides through high-throughput computational screening of over 67,000 known inorganic crystals in Materials Project. A dozen of them have been newly discovered and have not been reported before. Importantly, they possess completely different structural prototypes and properties of anionic electrons compared to widely studied electrides such as Ca2N. Finding these new vdW electrides expands the variety of electrides that can be made in the experiment and opens up new possibilities for studying their unique properties and applications.Then, based on the screened vdW electrides, we delve into their various emerging properties. For example, we developed a new magnetic mechanism specific to atomic-orbital-free ferromagnetism in electrides. We uncover the dual localized and extended nature of the anionic electrons in such electrides and demonstrate the formation of the local moment by the localized feature and the ferromagnetic interaction by the direct overlapping of their extended states. We further show the effective tuning of the magnetic properties of vdW electrides by engineering their structural, electronic, and compositional properties. Besides, we show that the complex interaction between the multiple quantum orderings in vdW electrides leads to many interesting properties including valley polarization, charge density waves, a topological property, a superconducting property, and a thermoelectrical property.Moreover, we discuss strategies to leverage the unique intrinsic properties of vdW electrides for practical applications. We show that these properties make vdW electrides potential candidates for advanced applications such as spin-orbit torque memory devices, valleytronic devices, K-ion batteries, and thermoelectricity. Finally, we discuss the current challenges and future perspectives for research using these emerging materials.

The specificities, influencing factors, and medical implications of bone circadian rhythms.

Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.

BTNL2 promotes colitis-associated tumorigenesis in mice by regulating IL-22 production.

Interleukin 22 (IL-22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL-22 production in the intestinal system is still unclear. Here, we present evidence that butyrophilin-like protein 2 (BTNL2) is required for colorectal IL-22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL-22. Mechanistically, BTNL2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote the production of IL-22. Importantly, we find that a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and that the mBTNL2-Fc recombinant protein has a therapeutic effect in a dextran sulfate sodium (DSS)-induced colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system but also provides a potential therapeutic target for the treatment of human colorectal cancer and inflammatory bowel diseases.

Mcrs1 regulates G2/M transition and spindle assembly during mouse oocyte meiosis.

Microspherule protein 1 (Mcrs1) is a component of the nonspecific lethal (NSL) complex and the chromatin remodeling INO80 complex, which participates in transcriptional regulation during mitosis. Here, we investigate the roles of Mcrs1 during female meiosis in mice. We demonstrate that Mcrs1 is a novel regulator of the meiotic G2/M transition and spindle assembly in mouse oocytes. Mcrs1 is present in the nucleus and associates with spindle poles and chromosomes of oocytes during meiosis I. Depletion of Mcrs1 alters HDAC2-mediated H4K16ac, H3K4me2, and H3K9me2 levels in nonsurrounded nucleolus (NSN)-type oocytes, and reduces CDK1 activity and cyclin B1 accumulation, leading to G2/M transition delay. Furthermore, Mcrs1 depletion results in abnormal spindle assembly due to reduced Aurora kinase (Aurka and Aurkc) and Kif2A activities, suggesting that Mcrs1 also plays a transcription-independent role in regulation of metaphase I oocytes. Taken together, our results demonstrate that the transcription factor Mcrs1 has important roles in cell cycle regulation and spindle assembly in mouse oocyte meiosis.

Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.

Rapid in situ RNA imaging based on Cas12a thrusting strand displacement reaction.

RNA In situ imaging through DNA self-assembly is advantaged in illustrating its structures and functions with high-resolution, while the limited reaction efficiency and time-consuming operation hinder its clinical application. Here, we first proposed a new strand displacement reaction (SDR) model (Cas12a thrusting SDR, CtSDR), in which Cas12a could overcome the inherent reaction limitation and dramatically enhance efficiency through energy replenishment and by-product consumption. The target-initiated CtSDR amplification was established for RNA analysis, with order of magnitude lower limit of detection (LOD) than the Cas13a system. The CtSDR-based RNA in situ imaging strategy was developed to monitor intra-cellular microRNA expression change and delineate the landscape of oncogenic RNA in 66 clinic tissue samples, possessing a clear advantage over classic in situ hybridization (ISH) in terms of operation time (1 h versus 14 h) while showing comparable sensitivity and specificity. This work presents a promising approach to developing advanced molecular diagnostic tools.

Topological Surface State Evolution in Bi2Se3 via Surface Etching.

Topological insulators are materials that have an insulating bulk interior while maintaining gapless boundary states against back scattering. Bi2Se3 is a prototypical topological insulator with a Dirac-cone surface state around Γ. Here, we present a controlled methodology to gradually remove Se atoms from the surface Se-Bi-Se-Bi-Se quintuple layers, eventually forming bilayer-Bi on top of the quintuple bulk. Our method allows us to track the topological surface state and confirm its robustness throughout the surface modification. Importantly, we report a relocation of the topological Dirac cone in both real space and momentum space as the top surface layer transitions from quintuple Se-Bi-Se-Bi-Se to bilayer-Bi. Additionally, charge transfer among the different surface layers is identified. Our study provides a precise method to manipulate surface configurations, allowing for the fine-tuning of the topological surface states in Bi2Se3, which represents a significant advancement toward nanoengineering of topological states.

Zn Single-Atom Catalysts Enable the Catalytic Transfer Hydrogenation of α,ß-Unsaturated Aldehydes.

Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.

REDalign: accurate RNA structural alignment using residual encoder-decoder network.

BACKGROUND: RNA secondary structural alignment serves as a foundational procedure in identifying conserved structural motifs among RNA sequences, crucially advancing our understanding of novel RNAs via comparative genomic analysis. While various computational strategies for RNA structural alignment exist, they often come with high computational complexity. Specifically, when addressing a set of RNAs with unknown structures, the task of simultaneously predicting their consensus secondary structure and determining the optimal sequence alignment requires an overwhelming computational effort of O ( L 6 ) for each RNA pair. Such an extremely high computational complexity makes these methods impractical for large-scale analysis despite their accurate alignment capabilities. RESULTS: In this paper, we introduce REDalign, an innovative approach based on deep learning for RNA secondary structural alignment. By utilizing a residual encoder-decoder network, REDalign can efficiently capture consensus structures and optimize structural alignments. In this learning model, the encoder network leverages a hierarchical pyramid to assimilate high-level structural features. Concurrently, the decoder network, enhanced with residual skip connections, integrates multi-level encoded features to learn detailed feature hierarchies with fewer parameter sets. REDalign significantly reduces computational complexity compared to Sankoff-style algorithms and effectively handles non-nested structures, including pseudoknots, which are challenging for traditional alignment methods. Extensive evaluations demonstrate that REDalign provides superior accuracy and substantial computational efficiency. CONCLUSION: REDalign presents a significant advancement in RNA secondary structural alignment, balancing high alignment accuracy with lower computational demands. Its ability to handle complex RNA structures, including pseudoknots, makes it an effective tool for large-scale RNA analysis, with potential implications for accelerating discoveries in RNA research and comparative genomics.

Iridium-Catalyzed Enantioselective Propargylic C-H Trifluoromethylthiolation and Related Processes.

The trifluoromethylthio group (SCF3) has gained increasing prominence in the field of drug design and development due to its unique electronic properties, remarkable stability, and high lipophilicity, but its derivatives remain challenging to access, especially in an enantioselective manner. In this Communication, we present an enantioselective iridium-catalyzed trifluoromethylthiolation of the propargylic C(sp3)-H bonds of alkynes. This protocol demonstrates its efficacy across a diverse array of alkyne substrates, including B- and Si-protected terminal alkynes as well as those derived from natural products and pharmaceuticals, to give trifluoromethyl thioethers with good to excellent yield and stereoselectivity. Moreover, this protocol could be modified to access enantioenriched difluoromethyl and chlorodifluoromethyl thioethers (SCF2H and SCF2Cl derivatives), significantly expanding the space of synthetically accessible enantioenriched fluoroorganic compounds.

Transition Metal Mimetic π-Activation by Cationic Bismuth(III) Catalysts for Allylic C-H Functionalization of Olefins Using C═O and C═N Electrophiles.

The discovery and utilization of main-group element catalysts that behave similarly to transition metal (TM) complexes have become increasingly active areas of investigation in recent years. Here, we report a series of Lewis acidic bismuth(III) complexes that allow for the catalytic allylic C(sp3)-H functionalization of olefins via an organometallic complexation-assisted deprotonation mechanism to generate products containing new C-C bonds. This heretofore unexplored mode of main-group reactivity was applied to the regioselective functionalization of 1,4-dienes and allylbenzene substrates. Experimental and computational mechanistic studies support the key steps of the proposed catalytic cycle, including the intermediacy of elusive Bi-olefin complexes and allylbismuth species.