Highlights d DRAK2 is markedly upregulated in the livers of both patients and mice with NAFLD/NASH d DRAK2 regulates RNA alternative splicing through SRPK1mediated SRSF6 phosphorylation d DRAK2 disturbs mitochondrial function in hepatic steatosis via RNA splicing machinery

We report an iridium(I)-catalyzed branched-selective C–H alkylation of N-arylisoindolinones with simple alkenes as the alkylating agents. The amide carbonyl group of the isoindolinone motif acts as the directing group to assist the ortho C–H activation of the N-aryl ring. With this atom-economic and highly branched-selective protocol, an array of biologically relevant N-arylisoindolinones were obtained in good yields. Asymmetric control was achieved with up to 87:13 er when a BiPhePhos-like chiral ligand was employed.

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