Cobalt-catalyzed Markovnikov-selective hydroamination of nonactivated olefins was developed. Hydrogen atom transfer from a catalytically generated cobalt(III)−hydride complex to the olefins proceeded regioselectively, and the nucleophilic addition of benzotriazoles occurred selectively at their N 2 -positions. The synthetic utility of the obtained N 2 -alkylated benzotriazoles as stable amine protecting groups under various reaction conditions was demonstrated, and the products were also transformed into primary amines by zinc-mediated reduction.

Herein, we describe the generation of an organochromium-type carbanion species from a non-activated C–H bond and its nucleophilic addition to aldehydes. The catalytic carbanion generation occurred through formal deprotonation of a non-activated C–H bond under mild conditions and did not need the prefunctionalization or anion stabilizing group. Carbon radical intermediates generated by decatungstate photocatalyst-mediated hydrogen abstraction were captured by a chromium salt with the reductive radical-polar crossover reaction to produce organochromium carbanions.

Despite their outstanding antitumour activity in mice, the limited supply from the natural sources has prevented drug discovery/development based on intact halichondrins. We achieved a total synthesis of C52-halichondrin-B amine (E7130) on a >10 g scale with >99.8% purity under GMP conditions. Interestingly, E7130 not only is a novel microtubule dynamics inhibitor but can also increase intratumoural CD31-positive endothelial cells and reduce α-SMA-positive cancer-associated fibroblasts at pharmacologically relevant compound concentrations. According to these unique effects, E7130 significantly augment the effect of antitumour treatments in mouse models and is currently in a clinical trial. Overall, our work demonstrates that a total synthesis can address the issue of limited material supply in drug discovery/development even for the cases of complex natural products.

A zirconium/nickel-mediated one-pot synthesis of ketones is reported. In the presence of Zn or Mn, Cp ZrCl was found to dramatically accelerate the coupling and suppress side product formation via an I→SPy displacement at the same time. Unlike Zn/Pd- and Fe/Cu-mediated one-pot ketone syntheses, the new method is effective for nucleophiles bearing OR or equivalent functional groups at the α-position. A mechanism comprising a nickel catalytic cycle, a zirconium catalytic cycle, and Zr→Ni transmetalation is proposed, and Cp ZrCl and/or low-valent Zr species are suggested to play crucial dual roles.

The structure and electronic nature of the phosphine have a significant influence on not only the formation, but also the subsequent transformation of O,P-acetals. The O,P-acetals generated from tris(o-tolyl)phosphine [(o-tol)(3)P] underwent efficient substitution reactions with various nucleophiles.