Supramolecular Catalyzed Cascade Reduction of Azaarenes Interrogated via Data Science.

Catalysis of multicomponent transformations requires controlled assembly of reactants within the active site. Supramolecular scaffolds possess synthetic microenvironments that enable precise modulation over noncovalent interactions (NCIs) engaged by reactive, encapsulated species. While molecular properties that describe the behavior of single guests in host cavities have been studied extensively, multicomponent transformations remain challenging to design and deploy.

Data Science-Enabled Palladium-Catalyzed Enantioselective Aryl-Carbonylation of Sulfonimidamides.

New methods for the general asymmetric synthesis of sulfonimidamides are of great interest due to their applications in medicinal chemistry, agrochemical discovery, and academic research. We report a palladium-catalyzed cross-coupling method for the enantioselective aryl-carbonylation of sulfonimidamides. Using data science techniques, a virtual library of calculated bisphosphine ligand descriptors was used to guide reaction optimization by effectively sampling the catalyst chemical space.

Coupling of α-bromoamides and unactivated alkenes to form γ-lactams through EDA and photocatalysis.

γ-Lactams are prevalent in small-molecule pharmaceuticals and provide useful precursors to highly substituted pyrrolidines. Despite numerous methods for the synthesis of this valuable motif, previous redox approaches to γ-lactam synthesis from α-haloamides and olefins require additional electron withdrawing functionality as well as -aryl substitution to promote electrophilicity of the intermediate radical and prevent competitive O-nucleophilicity about the amide. Using α-bromo imides and α-olefins, our strategy enables the synthesis of monosubstituted protected γ-lactams in a formal [3 + 2] fashion.

Iron-Catalyzed Photoinduced LMCT: a 1° C-H Abstraction Enables Skeletal Rearrangements and C(sp)-H Alkylation.

Herein we disclose an iron-catalyzed method to access skeletal rearrangement reactions akin to the Dowd-Beckwith ring expansion from unactivated C(sp)-H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates a chlorine radical, which abstracts electron-rich C(sp)-H bonds. The resulting unstable alkyl radicals can undergo rearrangement in the presence of suitable functionality.

Copper Catalyzed C(sp)-H Bond Alkylation via Photoinduced Ligand-to-Metal Charge Transfer.

Utilizing catalytic CuCl we report the functionalization of numerous feedstock chemicals via the coupling of unactivated C(sp)-H bonds with electron-deficient olefins. The active cuprate catalyst undergoes Ligand-to-Metal Charge Transfer (LMCT) to enable the generation of a chlorine radical which acts as a powerful hydrogen atom transfer reagent capable of abstracting strong electron-rich C(sp)-H bonds. Of note is that the chlorocuprate catalyst is an exceedingly mild oxidant (0.

Regioselective Alkylative Cross-Coupling of Remote Unactivated C()-H Bonds.

The functionalization of unactivated C()-H bonds poses a significant challenge due to their ubiquity and relative similarity in most organic frameworks. Herein, we describe the use of a combined photoredox and nickel catalytic system for the regioselective C()-C() coupling of unactivated C()-H bonds and alkyl bromides. Positional selectivity is dictated by a 1,5-hydrogen atom transfer (HAT) reaction by a pendent amide.