Visible-Light-Driven Decarboxylative Borylation: Rapid Access to α- and ß-Amino-boronamides.

In this study, we described a two-step process involving an efficient visible-light-induced decarboxylative borylation of α- and ß-amino redox-active esters with bis(catecholato)diboron, followed by transamination with 1,8-diaminonapthalene (DANH2). A series of boronamides were obtained in moderate to excellent yields in this one-pot procedure. The photochemical process proved to be very efficient even when conducted under flow conditions with shorter reaction durations and scalable synthesis of DAN boronates.

Catalytic synthesis of phenols with nitrous oxide.

The development of catalytic chemical processes that enable the revalorization of nitrous oxide (N2O) is an attractive strategy to alleviate the environmental threat posed by its emissions1-6. Traditionally, N2O has been considered an inert molecule, intractable for organic chemists as an oxidant or O-atom transfer reagent, owing to the harsh conditions required for its activation (>150 °C, 50‒200 bar)7-11. Here we report an insertion of N2O into a Ni‒C bond under mild conditions (room temperature, 1.5-2 bar N2O), thus delivering valuable phenols and releasing benign N2. This fundamentally distinct organometallic C‒O bond-forming step differs from the current strategies based on reductive elimination and enables an alternative catalytic approach for the conversion of aryl halides to phenols. The process was rendered catalytic by means of a bipyridine-based ligands for the Ni centre. The method is robust, mild and highly selective, able to accommodate base-sensitive functionalities as well as permitting phenol synthesis from densely functionalized aryl halides. Although this protocol does not provide a solution to the mitigation of N2O emissions, it represents a reactivity blueprint for the mild revalorization of abundant N2O as an O source.

Direct Photoexcitation of Ethynylbenziodoxolones: An Alternative to Photocatalysis for Alkynylation Reactions*.

Ethynylbenziodoxolones (EBXs) are commonly used as radical traps in photocatalytic alkynylations. Herein, we report that aryl-substituted EBX reagents can be directly activated by visible light irradiation. They act as both oxidants and radical traps, alleviating the need for a photocatalyst in several reported EBX-mediated processes, including decarboxylative and deboronative alkynylations, the oxyalkynylation of enamides and the C-H alkynylation of THF. Furthermore, the method could be applied to the synthesis of alkynylated quaternary centers from tertiary alcohols via stable oxalate salts and from tertiary amines via aryl imines. A photocatalytic process using 4CzIPN as an organic dye was also developed for the deoxyalkynylation of oxalates.

Dialkyl Ether Formation at High-Valent Nickel.

In this article, we investigated the I2-promoted cyclic dialkyl ether formation from 6-membered oxanickelacycles originally reported by Hillhouse. A detailed mechanistic investigation based on spectroscopic and crystallographic analysis revealed that a putative reductive elimination to forge C(sp3)-OC(sp3) using I2 might not be operative. We isolated a paramagnetic bimetallic NiIII intermediate featuring a unique Ni2(OR)2 (OR = alkoxide) diamond-like core complemented by a µ-iodo bridge between the two Ni centers, which remains stable at low temperatures, thus permitting its characterization by NMR, EPR, X-ray, and HRMS. At higher temperatures (>-10 °C), such bimetallic intermediate thermally decomposes to afford large amounts of elimination products together with iodoalkanols. Observation of the latter suggests that a C(sp3)-I bond reductive elimination occurs preferentially to any other challenging C-O bond reductive elimination. Formation of cyclized THF rings is then believed to occur through cyclization of an alcohol/alkoxide to the recently forged C(sp3)-I bond. The results of this article indicate that the use of F+ oxidants permits the challenging C(sp3)-OC(sp3) bond formation at a high-valent nickel center to proceed in good yields while minimizing deleterious elimination reactions. Preliminary investigations suggest the involvement of a high-valent bimetallic NiIII intermediate which rapidly extrudes the C-O bond product at remarkably low temperatures. The new set of conditions permitted the elusive synthesis of diethyl ether through reductive elimination, a remarkable feature currently beyond the scope of Ni.

Alkynylation of radicals: spotlight on the "Third Way" to transfer triple bonds.

The alkynylation of radical intermediates has been known since a long time, but had not been broadly applied in synthetic chemistry, in contrast to the alkynylation of either electrophiles or nucleophiles. In the last decade however, it has been intensively investigated leading to new disconnections to introduce versatile triple bonds into organic compounds. Nowadays, such processes are important alternatives to classical nucleophilic and electrophilic alkynylations. Efficient alkyne transfer reagents, in particular arylsulfones and hypervalent iodine reagents were introduced. Direct alkynylation, as well as cascade reactions, were subsequently developed. If relatively harsh conditions were required in the past, a new era began with progress in photoredox and transition metal catalysis. Starting from various radical precursors, alkynylations under very mild reaction conditions were rapidly discovered. This review covers the evolution of radical alkynylation, from its emergence to its current intensive stage of development. It will focus in particular on improvements for the generation of radicals and on the extension of the scope of radical precursors and alkyne sources.

C-Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation.

We report the first decarboxylative alkynylation of the C-terminus of peptides starting from free carboxylic acids. The reaction is fast, metal-free, and proceeds cleanly to afford alkynylated peptides with a broad tolerance for the C-terminal amino acid. By the use of hypervalent iodine reagents, the introduction of a broad range of functional groups was successful. C-terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine-tuned organic dyes.

Metal-Free Electrophilic Alkynylation of Sulfenate Anions with Ethynylbenziodoxolone Reagents.

Alkynyl sulfoxides are important building blocks with a unique reactivity in organic chemistry, but only a few reliable methods have been reported to synthesize them. A novel route to access alkynyl sulfoxides is reported herein by using ethynyl benziodoxolone (EBX) reagents to trap sulfenate anions generated in situ, via a retro-Michael reaction. The reaction takes place under metal-free and mild conditions. It is compatible with aryl, heteroaryl, and alkyl sulfoxides with up to 90% yield. This practical access to alkynyl sulfoxides is expected to facilitate the application of these useful building blocks in organic synthesis.

Revisiting the Urech Synthesis of Hydantoins: Direct Access to Enantiopure 1,5-Substituted Hydantoins Using Cyanobenziodoxolone.

A method for the synthesis of enantiopure 1,5-substituted hydantoins was developed using a hypervalent iodine cyanation reagent (cyanobenziodoxolone, CBX) as a source of electrophilic carbon. Starting from inexpensive commercially available enantiopure protected amino acids, the method allowed the synthesis of various hydantoins without epimerization. Formation of hydantoins from dipeptides was also possible, but partial epimerization was observed in this case. This synthetic strategy is user friendly as CBX is a bench-stable easy-to-handle crystalline reagent and avoids conventional multistep protocols, thus allowing the facile synthesis of a library of chiral hydantoins.

Fine-tuned organic photoredox catalysts for fragmentation-alkynylation cascades of cyclic oxime ethers.

Fine-tuned organic photoredox catalysts are introduced for the metal-free alkynylation of alkylnitrile radicals generated via oxidative ring opening of cyclic alkylketone oxime ethers. The redox properties of the dyes were determined by both cyclic voltammetry and computation and covered an existing gap in the oxidation potential of photoredox organocatalysts.

Divergent Access to (1,1) and (1,2)-Azidolactones from Alkenes using Hypervalent Iodine Reagents.

A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol(on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones.

Room temperature decarboxylative cyanation of carboxylic acids using photoredox catalysis and cyanobenziodoxolones: a divergent mechanism compared to alkynylation.

The one-step conversion of aliphatic carboxylic acids to the corresponding nitriles has been accomplished via the merger of visible light mediated photoredox and cyanobenziodoxolones (CBX) reagents. The reaction proceeded in high yields with natural and non-natural α-amino and α-oxy acids, affording a broad scope of nitriles with excellent tolerance of the substituents in the α position. The direct cyanation of dipeptides and drug precursors was also achieved. The mechanism of the decarboxylative cyanation was investigated both computationally and experimentally and compared with the previously developed alkynylation reaction. Alkynylation was found to favor direct radical addition, whereas further oxidation by CBX to a carbocation and cyanide addition appeared more favorable for cyanation. A concerted mechanism is proposed for the reaction of radicals with EBX reagents, in contrast to the usually assumed addition elimination process.

Synthesis of a 1,3-Bridged Macrobicyclic Enyne via Chemoselective Cycloisomerization Using Palladium-Catalyzed Alkyne-Alkyne Coupling.

A unique intramolecular Pd-catalyzed alkyne-alkyne coupling is presented. This transformation generates a strained, 1,3-bridged, macrocyclic enyne. The process was readily executed on gram scale, and the structure of the product was elucidated via X-ray crystallographic analysis. A mechanistic rationale for the observed chemoselectivity is provided.

Room-temperature decarboxylative alkynylation of carboxylic acids using photoredox catalysis and EBX reagents.

Alkynes are used as building blocks in synthetic and medicinal chemistry, chemical biology, and materials science. Therefore, efficient methods for their synthesis are the subject of intensive research. Herein, we report the direct synthesis of alkynes from readily available carboxylic acids at room temperature under visible-light irradiation. The combination of an iridium photocatalyst with ethynylbenziodoxolone (EBX) reagents allowed the decarboxylative alkynylation of carboxylic acids in good yields under mild conditions. The method could be applied to silyl-, aryl-, and alkyl- substituted alkynes. It was particularly successful in the case of α-amino and α-oxo acids derived from biomass.