Mary P. Watson

Within macrocyclic peptides of both natural products and pharmaceutical targets, aryl rings play a crucial role in linker structure, and C(sp3)-rich cyclophane linkers can imbue beneficial physicochemical properties. Yet, methods to deliver C(sp3)-rich cyclophane linkers remain limited, restricting the types of carbon-rich linkers that can be efficiently investigated in medicinal chemistry campaigns. Herein, we describe the development of a nickel-mediated deaminative macrocyclic arylation that uses amino acid monomers compatible with solid-phase peptide synthesis workflows, accommodates a wide range of peptide functionalities, and can access broad macrocycle architectures including those of a natural alkaloid derivative and polycyclic peptides.

Recognizing the potential of polymer-to-polymer transformations for plastics valorization, a new electrochemical strategy for the decarboxylative functionalization of polyacrylates has been developed.

We introduce a new 3,5-diphenylpyridinium motif that can be readily installed on α-tertiary alkyl amines and enables effective deamination. This advance overcomes the limitation that Katritzky pyridinium salts cannot be accessed from α-tertiary alkyl amines. Use of this 3,5-diphenylpyridinium salt enables a nickel-catalyzed reductive alkylation of Michael acceptors to construct quaternary carbons with a broad range of tertiary alkyl groups. Density functional theory (DFT) calculations were used to understand the surprising reactivity difference between adamantyl and other tertiary alkyl groups.

Nickel-catalyzed, stereospecific cross-couplings via activation of secondary C–O bonds have been well developed in the past few years. Meanwhile, stereospecific cross-couplings of tertiary electrophiles have rarely been explored. Herein, we describe a nickel-catalyzed, ligand-free Suzuki–Miyaura vinylation, using easily prepared, highly enantioenriched tertiary benzylic carboxylates to install quaternary stereocenters in high yields and ee’s. This method allows stereospecific vinylation of these substrates for the first time and is a rare example of stereospecific coupling that overcomes the requirement for a naphthyl group on the benzylic carboxylate.

Single-use hygiene products account for a significant volume of landfill waste, and valorization of their superabsorbent polymer component, poly(acrylic acid) (PAA), via a polymer-to-polymer transformation has been targeted. Herein, we report the photoredox-catalyzed decarboxylative fluorination of PAA using riboflavin, a sustainable and economical organophotocatalyst. Our approach enables the synthesis of copolymers of PAA and poly(vinyl fluoride) (PVF), valuable commodity materials, in less than one hour of irradiation. Additionally, the process uses water as solvent, applies to PAA substrates of various molecular weights, enables tunable conversion on the basis of irradiation time, and can employ riboflavin from a commercial vitamin B2 capsule as catalyst.

Aliphatic amino alcohols such as 6-amino-1-hexanol are potential platform chemicals for a variety of advanced materials. Selective enzymatic synthesis from biomass-derived diols could simplify production while minimizing hazards.