Ruthenium-catalyzed C-H functionalization was successfully combined with palladium-catalyzed asymmetric allylic alkylation in one pot. The novel dual-metal-catalyzed reaction provides a variety of 3-allyl-3-aryl oxindoles from the corresponding α-diazoamides in up to 99% yield with up to 85% ee. The appropriate ligand choice is important to promote the sequential reaction, avoiding undesired metal interaction or ligand exchange.

Summary Ivacaftor (VX-770) was the first cystic fibrosis transmembrane conductance regulator (CFTR) modulatory drug approved for the treatment of patients with cystic fibrosis. Electron cryomicroscopy (cryo-EM) studies of detergent-solubilized CFTR indicated that VX-770 bound to a site at the interface between solvent and a hinge region in the CFTR protein conferred by transmembrane (tm) helices: tm4, tm5, and tm8. We re-evaluated VX-770 binding to CFTR in biological membranes using photoactivatable VX-770 probes. One such probe covalently labeled CFTR at two sites as determined following trypsin digestion and analysis by tandem-mass spectrometry. One labeled peptide resides in the cytosolic loop 4 of CFTR and the other is located in tm8, proximal to the site identified by cryo-EM. Complementary data from functional and molecular dynamic simulation studies support a model, where VX-770 mediates potentiation via multiple sites in the CFTR protein.

Molecular intelligence: The structurally novel lignan (+)‐linoxepin is synthesized in an eight‐step sequence. The enantioselective synthesis features the palladium‐catalyzed Catellani reaction as the key step. In this highly convergent multicomponent reaction, two new carbon–carbon bonds are formed, one of which results from a CH bond functionalization.

Cycloadditions are powerful processes to synthesize complex polycyclic scaffolds. Herein, we disclose a [4+3]‐cycloaddition between an in situ generated ortho‐quinone methide and an isomünchnone to yield oxa‐bridged oxazocine cores, generating N2 and H2O as the sole by‐products. Using only catalytic amounts of camphorsulfonic acid, it is possible to generate both reactive intermediates in one step, eliminating the need for rhodium catalysts generally employed for isomünchnone formation. Spectroscopic data and X‐ray crystallography indicate the formation of the syn diastereomer, with the main side‐product arising from a hydrate participating in a competing [4+2]‐cycloaddition pathway.

Compatible combinations of achiral and chiral ligands can be used in rhodium/palladium catalysis to achieve highly enantioselective domino reactions. The difference in rates of catalysis and minimal effects of ligand interference confer control in the domino sequence. The "all-in-one" 1,4-conjugate arylation and C-N cross-coupling through sequential Rh/Pd catalysis provides access to enantioenriched dihydroquinolinone building blocks.