SHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, is involved in multiple cell signaling processes including Ras/MAPK and Hippo/YAP pathways. SHP2 has been shown to contribute to the progression of a number of cancer types including leukemia, gastric, and breast cancers. It also regulates T-cell activation by interacting with inhibitory immune checkpoint receptors such as the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA). Thus, SHP2 inhibitors have drawn great attention by both inhibiting tumor cell proliferation and activating T cell immune responses toward cancer cells. In this study, we report the identification of an allosteric SHP2 inhibitor 1-(4-(6-bromonaphthalen-2-yl)thiazol-2-yl)-4-methylpiperidin-4-amine (23) that locks SHP2 in a closed conformation by binding to the interface of the N-terminal SH2, C-terminal SH2, and phosphatase domains. Compound 23 suppresses MAPK signaling pathway and YAP transcriptional activity and shows antitumor activity in vivo. The results indicate that allosteric inhibition of SHP2 could be a feasible approach for cancer therapy.

Herein we report a highly selective photoredox C(sp3)−H alkylation/arylation of ethers through the combination of a photo‐organocatalyst (benzaldehyde) and a transition‐metal catalyst (nickel). This method provides a simple and general strategy for the C(sp3)−H alkylation/arylation of ethers. A selective late‐stage modification of (−)‐ambroxide has also been conducted to demonstrate the applicability of the method.

Geminal diboronates have attracted significant attention because of their unique structures and reactivity. However, benzofuran-, indole-, and benzothiophene-based benzylic gem-diboronates, building blocks for biologically relevant compounds, are unknown. A promising protocol using visible light and aryl iodides for constructing valuable building blocks, including benzofuran-, indole-, and benzothiophene-based benzylic gemdiboronates, via radical carbo-cyclization/gem-diborylation of alkynes with a high functional group tolerance is presented. The utility of these gem-diboronates has been demonstrated by a 10 g scale conversion, by versatile transformations, by including the synthesis of approved drug scaffolds and two approved drugs, and even by polymer synthesis. The mechanistic investigation indicates that the merging of the dinuclear gold catalyst (photoexcitation by 315−400 nm UVA light) with Na 2 CO 3 is directly responsible for photosensitization of aryl iodides (photoexcitation by 254 nm UV light) with blue LED light (410−490 nm, λ max = 465 nm) through an energy transfer (EnT) process, followed by homolytic cleavage of the C−I bond in the aryl iodide substrates.

[Au2(μ-dppm)2]­Cl2-mediated photocatalysis reactions are usually initiated by ultraviolet A (UVA) light; herein, an unreported system using blue light-emitting diodes (LEDs) as excitation light source was found. The red shift of the absorption wavelength originates from the combination of [Au2(μ-dppm)2]­Cl2 and ligand (Ph3P or mercaptan). On the basis of this finding, a gold-catalyzed reductive desulfurizing C–C coupling of electrophilic radicals and styrenes mediated by blue LEDs is presented, a coupling which cannot be efficiently accessed by previously reported methods. This mild and highly efficient C–C bond formation strategy uses mercaptans both as electron-deficient alkyl radical precursor as well as the hydrogen source. Two examples of amino acids have also been modified by using this strategy. Moreover, this methodology could be applied in polymer synthesis. Gram-scale synthesis and mechanistic insights into this transformation are also presented.

Herein a synergistic combination of a nickel catalyst and benzaldehyde for the utilization of amides and thioethers in C(sp 3 )−H alkylation and arylation reactions employing simple aryl or alkyl halides is reported. This method provides a simple and cheap strategy for the direct functionalization of amides and thioethers. Readily available starting materials, mild reaction conditions, a good functionalgroup tolerance, and a broad substrate scope make this methodology attractive and practical for pharmaceutical and synthetic chemistry.