Facile Preparation of Spirolactones by an Alkoxycarbonyl Radical Cyclization-Cross-Coupling Cascade.

An alkoxycarbonyl radical cyclization-cross-coupling cascade has been developed that allows functionalized γ-butyrolactones to be prepared in one step from simple tertiary alcohol-derived homoallylic oxalate precursors. The reaction succeeds with aryl and vinyl electrophiles and is compatible with heterocyclic fragments in both coupling partners. This chemistry allows for the rapid construction of spirolactones, which are of interest in drug discovery endeavors

Forging C(sp3)-C(sp3) Bonds with Carbon-Centered Radicals in the Synthesis of Complex Molecules.

Radical fragment coupling reactions that unite intricate subunits have become an important class of transformations within the arena of complex molecule synthesis. This Perspective highlights some of the early contributions in this area, as well as more modern applications of radical fragment couplings in the preparation of natural products. Additionally, emphasis is placed on contemporary advances that allow for radical generation under mild conditions as a driving force for the implementation of radical fragment couplings in total synthesis

Forging C(sp3)-C(sp3) Bonds with Carbon-Centered Radicals in the Synthesis of Complex Molecules.

Radical fragment coupling reactions that unite intricate subunits have become an important class of transformations within the arena of complex molecule synthesis. This Perspective highlights some of the early contributions in this area, as well as more modern applications of radical fragment couplings in the preparation of natural products. Additionally, emphasis is placed on contemporary advances that allow for radical generation under mild conditions as a driving force for the implementation of radical fragment couplings in total synthesis

Total synthesis of (-)-N-methylwelwitindolinone B isothiocyanate via a chlorinative oxabicycle ring-opening strategy.

The first total synthesis of N-methylwelwitindolinone B isothiocyanate is reported. The route features several key steps, including a regio- and diastereoselective chlorinative oxabicycle ring-opening reaction to introduce the challenging alkyl chloride motif

Enantiospecific Total Synthesis of N‐Methylwelwitindolinone D Isonitrile

The total synthesis of N-methylwelwitindolinone D isonitrile (1) has been achieved in 17 steps from a readily available carvone derivative. The route features a double C-H functionalization event involving a keto oxindole substrate to introduce the tetrahydrofuran ring of the natural product

Nickel-Catalyzed Alkylation of Amide Derivatives

We report the catalytic alkylation of amide derivatives, which relies on the use of nonprecious metal catalysis. Amide derivatives are treated with organozinc reagents, utilizing nickel catalysis, to yield ketone products. The methodology is performed at ambient temperature and is tolerant of variation in both coupling partners. A precursor to a nanomolar glucagon receptor modulator was synthesized using the methodology, underscoring the mild nature of this chemistry and its potential utility in pharmaceutical synthesis. These studies are expected to further promote the use of amides as synthetic building blocks

Benchtop Delivery of Ni(cod)₂ using Paraffin Capsules

A facile method that allows for Ni­(cod)₂ to be used on the benchtop is reported. The procedure involves the preparation of paraffin–Ni­(cod)₂ capsules, which are stable to air and moisture. It is demonstrated that these readily available capsules can be used to promote a range of Ni­(cod)₂-catalyzed transformations. These studies are expected to promote the further use of Ni­(cod)₂ in organic synthesis