Selective C-H Activation of Molecular Nanodiamonds via Photoredox Catalysis.

While substituted adamantanes have widespread use in medicinal chemistry, materials science, and ligand design, the use of diamantanes and higher diamondoids is limited to a much smaller number. Selective functionalization beyond adamantane is challenging, as the number of very similar types of C-H bonds (secondary, 2°, and tertiary, 3°) increases rapidly, and H atom transfer does not provide a general solution for site selectivity. We report a method using pyrylium photocatalysts that is effective for nanodiamond functionalization in up to 84% yield with exclusive 3° selectivity and moderate levels of regioselectivity between 3° sites. The proposed mechanism involving photooxidation, deprotonation, and radical C-C bond formation is corroborated through Stern-Volmer luminescence quenching, cyclic voltammetry, and EPR studies. Our photoredox strategy offers a versatile approach for the streamlined synthesis of diamondoid building blocks.

Direct radical functionalization methods to access substituted adamantanes and diamondoids.

Adamantane derivatives have diverse applications in the fields of medicinal chemistry, catalyst development and nanomaterials, owing to their unique structural, biological and stimulus-responsive properties, among others. The synthesis of substituted adamantanes and substituted higher diamondoids is frequently achieved via carbocation or radical intermediates that have unique stability and reactivity when compared to simple hydrocarbon derivatives. In this review, we discuss the wide range of radical-based functionalization reactions that directly convert diamondoid C-H bonds to C-C bonds, providing a variety of products incorporating diverse functional groups (alkenes, alkynes, arenes, carbonyl groups, etc.). Recent advances in the area of selective C-H functionalization are highlighted with an emphasis on the H-atom abstracting species and their ability to activate the particularly strong C-H bonds that are characteristic of these caged hydrocarbons, providing insights that can be applied to the C-H functionalization of other substrate classes.

Synthesis of amino-diamondoid pharmacophores via photocatalytic C-H aminoalkylation.

We report a direct C-H aminoalkylation reaction using two light-activated H-atom transfer catalyst systems that enable the introduction of protected amines to native adamantane scaffolds with C-C bond formation. The scope of adamantane and imine reaction partners is broad and deprotection provides versatile amine and amino acid building blocks. Using readily available chiral imines, the enantioselective synthesis of the saxagliptin core and rimantadine derivatives is also described.