Herein, we report the first total syntheses of complex cephalotaxus diterpenoids cephanolide B and C from commercially available 5-bromo-2-methylanisole. Key to the success of this synthetic route is a palladium-catalyzed cascade cyclization reaction, which allowed us to efficiently forge the 6-5-6 cis-fused tricyclic ring systems found in the entire family of cephalotaxus diterpenoids. Additionally, site-selective late-stage sp C-H bond oxidation served as a key strategic element in the chemical synthesis of cephanolide C.

Nucleophilic aromatic substitution (SNAr) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron‐deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic SNAr reactions. The method is applicable to a broad array of electron‐rich and neutral aryl fluorides, which are inert under classical SNAr conditions. Although the mechanism of SNAr reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise‐like energy profile. Notably, we isolated a rhodium η5‐cyclohexadienyl complex intermediate with an sp3‐hybridized carbon bearing both a nucleophile and a leaving group.

A four-step total synthesis of paeoveitol (1), a recently disclosed norditerpene natural product from Paeonia vetchii, is reported. This highly concise synthetic route was guided by biosynthetic considerations and enabled by an unusual intermolecular ortho-quinone methide [4 + 2]-cycloaddition reaction, which proceeded with excellent regio- and diastereoselectivity. Density functional theory (DFT) calculations point to a crucial intermolecular hydrogen bond and π-π stacking interaction that govern selectivity in this process.

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Hydroalkylation, the direct addition of a C(sp3)–H bond across an olefin, is a desirable strategy to produce valuable, complex structural motifs in functional materials, pharmaceuticals, and natural products. Herein, we report a reliable method for accessing α-branched amines via nickel-catalyzed hydroalkylation reactions. Specifically, by using bis(cyclooctadiene)nickel (Ni(cod)2) together with a phosphine ligand, we achieved a formal C(sp3)–H bond insertion reaction between olefins and N-sulfonyl amines without the need for an external hydride source. The amine not only provides the alkyl motif but also delivers hydride to the olefin by means of a nickel-engaged β–hydride elimination/reductive elimination process. This method provides a platform for constructing chiral α-branched amines by using a P-chiral ligand, demonstrating its potential utility in organic synthesis. Notably, a sulfonamidyl boronate complex formed in situ under basic conditions promotes ring-opening of the azanickellacycle reaction intermediate, leading to a significant improvement of the catalytic efficiency.