Decarboxylative coupling of carboxylic acids with activated olefins has been accomplished using visible light photoredox catalysis. The strategic placement of a radical-stabilizing aromatic group at the β-position of the olefin component biases the regioselectivity of the addition, allowing reliable, facile access to anti-Michael-type products from readily available precursors. The scope of this methodology was demonstrated with a range of carboxylic acids and appropriately substituted olefins and was applied toward a two-step synthesis of the antiarrhythmic agent encainide.

We disclose a novel radical strategy for the fluorination of alkyl bromides via the merger of silyl radical-mediated halogen-atom abstraction and benzo­phenone photosensitization. Selectivity for halogen-atom abstraction from alkyl bromides is observed in the presence of an electrophilic fluorinating reagent containing a weak N–F bond despite the predicted favorability for Si–F bond formation. To probe this surprising selectivity, preliminary mechanistic and computational studies were conducted, revealing that a radical chain mechanism is operative in which kinetic selectivity for Si–Br abstraction dominates due to a combination of polar effects and halogen-atom polarizability in the transition state. This transition-metal-free fluorination protocol tolerates a broad range of functional groups, including alcohols, ketones, and aldehydes, which demonstrates the complementary nature of this strategy to existing fluorination technologies. This system has been extended to the generation of gem-difluorinated motifs which are commonly found in medicinal agents and agrochemicals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of the COVID-19 pandemic, remains a global medical problem. Angiotensin-converting enzyme 2 ( ACE2 ) was identified as the primary viral entry receptor, and transmembrane serine protease 2 primes the spike protein for membrane fusion. However, ACE2 expression is generally low and variable across tissues, suggesting that auxiliary receptors facilitate viral entry. Identifying these factors is critical for understanding SARS-Cov-2 pathophysiology and developing new countermeasures. However, profiling host–virus interactomes involves extensive genetic screening or complex computational predictions. Here, we leverage the photocatalytic proximity labeling platform μMap to rapidly profile the spike interactome in human cells and identify eight novel candidate receptors. We systemically validate their functionality in SARS-CoV-2 pseudoviral uptake assays with both Wuhan and Delta spike variants and show that dual expression of ACE2 with either neuropilin-2, ephrin receptor A7, solute carrier family 6 member 15, or myelin and lymphocyte protein 2 significantly enhances viral uptake. Collectively, our data show that SARS-CoV-2 synergistically engages several host factors for cell entry and establishes μMap as a powerful tool for rapidly interrogating host–virus interactomes.

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