Metal-Free Photoinduced Decarboxylative Radical Polymerization Using Carboxylic Acids as Benign Radical Initiators: Introduction of Complex Molecules into Polymer Chain Ends

Abstract

Metal-free photoinduced decarboxylative radical polymerization of aliphatic carboxylic acids with a variety of monomers was found to proceed smoothly to give the corresponding polymers under mild conditions. Complex carboxylic acids such as those of sugars, steroids, and peptides can function as benign radical initiators via decarboxylation and can be incorporated at the polymer chain ends. This synthetic methodology represents a facile introduction of molecules and functionalities to polymers by using commercially available carboxylic acids.

Decarboxylative couplings as versatile tools for late‐stage peptide modifications

“…Finally the free radical polymerization of a tripeptide bearing a free side‐chain glutamic acid with excess methyl acrylate (100 equiv.) afforded peptide‐capped polymer 109 , with an average molecular weight M n = 9400 . Notably, the polymerization also proceeded with α‐acids, demonstrating the versatility of the phen/1,4‐DCB reaction system for mild and general decarboxylative modifications.…”

“…Such methods facilitate the formation of diverse CC bonds, including C‐terminal decarboxylative alkylation and arylation, as well as strategies for Cheteroatom bond formation. Application of these methodologies to the versatile synthesis of unnatural amino acids, peptide macrocycles, peptide functionalized polymers, and even proteins is a powerful testament to the robust nature of the coupling strategies. The majority of available methods utilize photocatalytic and, in some cases, electrochemical approaches to convert carboxylic acids under mild conditions into the corresponding peptide alkyl radicals following the extrusion of CO 2 .…”

Recent Advances in Photoredox Catalysis Enabled Functionalization of α-Amino Acids and Peptides: Concepts, Strategies and Mechanisms

“…The phenanthryl radical cation is a powerful oxidant and subsequently oxidizes, for example, the peptide carboxylate, resulting in extrusion of CO 2 to furnish the corresponding alkyl radical, which can engage in a variety of ensuing radical manifolds. [139][140][141][142][143][144][145][146][147][148][149][150][151][152] The visible-light-mediated direct decarboxylative conjugate addition previously developed by the MacMillan group (see Scheme 10) was also instrumental in their discovery that this reactivity is not limited to simple -amino acids and dipeptides, but can also be exploited for site-and chemoselective functionalization of peptides and proteins (Scheme 36). 153 Initial evaluations on achieving selective Cterminal decarboxylative functionalization of tetrapeptides using photocatalyst 2; however, this proved to be less than fruitful.…”

Transition-Metal-Free Access to 2-Subsituted Indolines from Indoles via Dearomative Nucleophilic Addition Using Two-Molecule Organic Photoredox Catalysts

“…With the aim of developing synthetic approaches that utilize less toxic and more readily available reagents under mild conditions, we have been investigating photochemical reactions using organic photoredox catalysts, as they constitute environmentally friendly methods wherein light is applied as a traceless reagent, and harsh reaction conditions, such as high temperature and pressure, are not required. We have recently reported photoinduced electron transfer (PET)-promoted reactions of carboxylic acids [21][22][23][24][25][26][27], arylboronic acids [28], indene [29,30], and electron-rich alkenes [31] catalyzed by two-molecule organic photoredox catalysts, such as a combination of phenanthrene (Phen) as an electron donor and 1,4-dicyanobenzene (1,4-DCB) as an electron acceptor, under UV irradiation (313 nm) (Scheme 1b). This finding encouraged us to explore the PET-promoted decarboxylation of amino acids and peptides for their modification [32][33][34][35].…”