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A palladium-catalyzed ortho-silylation of aryl iodides/arylsilylation of oxanorbornadiene/retro-Diels-Alder domino reaction was developed. Such a transformation provides access to various functionalized ( Z)-β-substituted vinylsilanes with exclusive selectivity using hexamethyldisilane as a bis-silylation reagent and 2,3-dicarbomethoxy-7-oxanorbornadiene (ONBD) as an ortho-C-H activator and ethylene surrogate. A variety of ( Z)-β-substituted vinylgermanes and ( Z)-β-substituted vinylstannanes were also obtained under mild reaction conditions. This atom-economical, stereoselective, and scalable approach is compatible with a diverse range of readily available functionalized aryl iodides.

Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.

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In this work, we describe a Catellani-type C−H glycosylation to provide rapid access to various highly decorated α-C-(hetero)aryl glycosides in a modular and stereoselective manner (>90 examples). The termination step is flexible, which is demonstrated by ipso-Heck reaction, hydrogenation, Suzuki coupling, and Sonogashira coupling. Application of this methodology has been showcased by preparing glycoside−pharmacophore conjugates and a dapagliflozin analogue. Notably, the technology developed herein represents an unprecedented example of Catellani-type alkylation involving an S N 1 pathway.

A palladium/DPEphos-catalyzed intermolecular trans-selective carbofunctionalization of internal alkynes has been established herein. This method proceeds through a formal anticarbopalladation, forming trans-alkenyl palladium species, which was trapped by aryl boronic acids to provide all-carbon tetrasubstituted alkenes in 32−92% yields. The trans-selective arylsilylation/remote C−H silylation and hydroarylation/remote C−H borylation of internal alkynes were also achieved using hexamethyldisilane and bis(pinacolato)diboron as trapping reagents, respectively. The reaction features good regio-and stereoselectivity and high functional group tolerance. A preliminary mechanistic study and DFT calculations show that a cis to trans isomerization of cis-alkenyl palladium species was involved in this transformation.