Application of Ni/Zr-Mediated Ketone Coupling for the Scalable Synthesis of Homohalichondrin B.

A practical and improved synthetic route for the scalable synthesis of homohalichondrin B has been developed. Formation of the highly stereoselective [6,6]-spiroskeleton system through a convergent Ni/Zr-mediated ketone coupling, followed by acid-promoted spiroketalization, simplified the route considerably. Higher coupling efficiency was achieved by fine-tuning the Ni/Ni (1:50) catalyst loadings with an equimolar (1:1) mixture of coupling partners.

Aminative Suzuki-Miyaura coupling.

The Suzuki-Miyaura and Buchwald-Hartwig coupling reactions are widely used to form carbon-carbon (C-C) and carbon-nitrogen (C-N) bonds, respectively. We report the incorporation of a formal nitrene insertion process into the Suzuki-Miyaura reaction, altering the products from C-C-linked biaryls to C-N-C-linked diaryl amines and thereby joining the Suzuki-Miyaura and Buchwald-Hartwig coupling pathways to the same starting-material classes. A combination of a bulky ancillary phosphine ligand on palladium and a commercially available amination reagent enables efficient reactivity across aryl halides and pseudohalides, boronic acids and esters, and many functional groups and heterocycles.

Nickel-Catalyzed Deaminative Ketone Synthesis: Coupling of Alkylpyridinium Salts with Thiopyridine Esters via C-N Bond Activation.

A direct synthesis of ketones by the nickel-catalyzed deaminative cross-coupling of alkylpyridinium salts with thiopyridine esters has been reported. The reaction works well for both primary and secondary amines. This approach affords a highly valuable vista for the facile synthesis of ketones from easily accessible feedstock chemicals.

Toward the synthesis of the hypoxia selective anticancer agent BE-43547 A.

A short and enantioselective synthesis of the 19--BE-43547 A chiral framework has been achieved in a high yield. The challenging key C15 tertiary stereocenter was derived from D-glucose. The synthetic strategy involves a Julia-Kocienski olefination to install the lipophilic side chain.

Insertion of N-Tosylacetimidates/Acetimidamides onto Arynes via [2 + 2] Cycloaddition.

A novel insertion reaction of N-tosylacetimidates and N-tosylacetimidamides onto arynes via a benzocyclobutene intermediate followed by ring cleavage is developed to afford o-benzylbenzoic acid derivatives in good yields. Interestingly, the use of cyclic 2-sulfonyliminoindolines provided two distinct products such as azepanimines via [2 + 2] cycloaddition and indolamines via protonation based on solvent medium.