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 NiI/NiII (1:50) catalyst loadings with an equimolar (1:1) mixture of coupling partners.

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. The utility of this method is demonstrated through the functionalization of complex bioactives and pharmaceuticals.

Toward the synthesis of the hypoxia selective anticancer agent BE-43547 A2.

A short and enantioselective synthesis of the 19-epi-BE-43547 A2 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. An efficient protocol for Z to E isomerization of olefin was developed using a novel UV flow reactor. In addition, an unprecedented oxygen mediated hydroboration and the Krapcho decarboxylation of ß-keto lactone were observed.

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.