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.

Photoinduced debenzylations of phenylalanine and tyrosine derivatives with dicyanoarenes afford glycine derivatives by the generation of radical cations. Despite the limited substrate scope, the radical cation of phenylalanine and tyrosine derivatives bearing both a carbamate (without an aromatic group) at the N-terminal and an amide at the C-terminal could promote the breaking C–C bond at the benzylic position by a photoinduced electron transfer. It is important to understand the chemical behavior of the radical cations of phenylalanine and tyrosine in enzymes involving electron transfer.Download high-res image (168KB)Download full-size image

•A new method for radical reactions of aliphatic carboxylic acids via PET-promoted decarboxylation is described.•Stable, inexpensive, and neutral organic molecules are employed as the photocatalyst to generate alkyl radicals.•A variety of radical reactions are successfully performed to show a unique reactivity.This feature article covers our efforts to develop a new method for radical reactions of aliphatic carboxylic acids via a photoinduced electron transfer-promoted decarboxylation using an organic photoredox system. Stable, inexpensive, and neutral organic molecules, such as phenanthrene and 1,4-dicyanobenzene, are employed as the photocatalyst to generate alkyl radicals. The photoinduced decarboxylative radical reactions are proven to be useful for reduction, deuteration, addition to CC, CN, and CO double bonds, modification of peptides, cyclization, ring expansion, substitution of dicyanobenzenes, and formation of a carbanion under mild conditions.Download high-res image (161KB)Download full-size image

•N-Acryloyl amino acid esters and peptides can be utilized as radical acceptors in the PET induced decarboxylation reaction.•The photoreaction afforded modified amino acids and peptides under mild reaction conditions.•This methodology can provide decarboxylated coupling peptides containing γ-amino acids.The photoinduced electron transfer (PET) promoted decarboxylative radical additions of carboxylic acids using N-acryloyl amino acid esters and peptides as radical acceptors smoothly afforded the corresponding modified amino acids and peptides under mild reaction conditions. The radical additions of α-amino acids led to the formation of γ- and α-dipeptide, and peptides underwent peptide coupling via decarboxylation.

•Use of FEP millitube reactor significantly improved the efficiency of photoreactions.•Sunlight-induced photoreaction is achieved using FEP millitube reactor.•This method generates alkyl radicals from carboxylic acids under mild conditions.The use of a fluorinated ethylene propylene (FEP) millitube reactor significantly improved the efficiency of the photoinduced decarboxylative radical addition of aliphatic carboxylic acids to electron-deficient alkenes, producing the corresponding γ-amino acid derivative and macrocyclic lactone. These sunlight-induced photoreactions were achieved using a millitube reactor, even though the photosensitizer used in this system absorbs only UV light.

Sequential hydrolysis and photoinduced decarboxylation of methyl aliphatic esters lead to efficient generation of alkyl radicals under mild conditions. The generated alkyl radicals react with a variety of reagents to produce addition, reduction, and substitution products. In addition, the new tin and halogen free process for alkyl radical generation is applicable to a variety of aliphatic esters including those of dipeptides, steroids, saccharides, and lactones.

In order to explore the applicability of photoinduced electron transfer (PET) promoted decarboxylative reactions to the direct modification of peptides, a study was performed to assess the influence of amino acid side chains on photoreactions of N-terminal protected tripeptides. Photoinduced decarboxylation reactions of tripeptides, which are composed of central amino acids that possess alkyl, phenyl, thioether, hydroxy, and amide containing side chains, in the presence or absence of acrylonitrile and a thiol were found to proceed smoothly to give the corresponding radical addition, H-abstraction, and substitution products. Although photoreactions of tripeptides containing central amino acids with phenol and indole (Tyr and Trp) moieties do not take place efficiently, appropriate protection of these groups enables the substrates to undergo smooth photoinduced decarboxylative reactions.

A simple method has been developed for the efficient synthesis of naphtho[b]furans from allyl bromonaphthyl ethers. The approach utilizes a novel photochemical process involving sequential radical cyclization and dehydrohalogenation. Because light is a readily available, environmentally friendly reagent that produces no by-products, the new process serves as a green synthetic method.

Photoinduced electron transfer (PET) promoted decarboxylation of α-(ω-carboxyalkyl) β-keto esters undergoes radical ring expansion and cyclization reactions. This mild and environmentally friendly method can provide one-carbon expanded γ-keto esters and bicyclic alcohols, and the product distribution is strongly dependent on the length of the alkyl chain containing the terminal carboxylate group.

Tin-free, photoinduced electron transfer promoted reductive radical cyclization reactions of allyl 2-bromoaryl ethers in the presence of NaOH in 2-PrOH were found to take place efficiently to give 3-methyl-2,3-dihydrobenzofurans. In contrast to conventional radical cyclization reactions that employ AIBN/Bu3SnH in benzene, the new method utilizes NaOH and 2-PrOH that are both readily available and benign. Consequently, the newly developed photochemical process serves as a versatile and environmentally friendly method for carrying out aryl radical cyclization reactions.

Photoinduced electron transfer (PET)-promoted decarboxylation of aliphatic carboxylic acids using catalytic amounts of an arene and electron-acceptor (>2.5 mol %) was found to proceed efficiently to give adducts even when only 1 equiv of acrylonitrile was employed. The use of catalytic quantities of the arene and electron-acceptor demonstrates that the yield of the adduct is strongly influenced by the efficiency of back electron transfer from the radical anion of the electron-acceptor to radical intermediate 1.

A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,β-unsaturated carbonyl moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of carboxylic acid tethered acryl amide or α,β-unsaturated ketone moieties, which were also prepared starting from the macrocyclic lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.

Radical addition to a glyoxylic oxime ether was accomplished under mild conditions using an alkyl radical generated from a free carboxylic acid via photochemical decarboxylation. The photoreaction provided an efficient route to α-substituted α-aminoesters from carboxylic acids and oxime ether.

Inter- and intramolecular additions of alkyl radicals, generated by SET photochemical decarboxylation reactions of free carboxylic acids, to electron-deficient alkenes take place under mild conditions as part of efficient routes for the formation of N-Boc γ-amino acids and macrocyclic lactones.

•Reductive ipso-radical cyclization onto benzene ring by alkyl radical is achieved.•Substrates are limited to five-membered aliphatic carboxylic acids.•Tetracyclic spiro dihydroisoquinolinones can be prepared in one-step.A new radical cyclization has been developed for the one-step synthesis of spiro dihydroisoquinolinone derivatives from alicyclic amino acids bearing N-(2-phenyl)benzoyl groups through photoinduced electron transfer (PET)-promoted decarboxylation. Reductive ipso-radical cyclization onto a benzene ring by an alkyl radical is achieved under mild conditions for the first time, although the substrates are limited to five-membered aliphatic carboxylic acids bearing N-(2-phenyl)benzoyl groups.