Photoredox/Brønsted Acid Co-Catalysis Enabling Decarboxylative Coupling of Amino Acid and Peptide Redox-Active Esters with N‑Heteroarenes

An iridium photoredox catalyst in combination with a phosphoric acid catalyzes the decarboxylative α-aminoalkylation of natural and unnatural α-amino acid-derived redox-active esters (<i>N</i>-hydroxyphthalimide esters) with a broad substrate scope of N-heteroarenes at room temperature under irradiation. Dipeptide- and tripeptide-derived redox-active esters are also amenable substrates to achieve decarboxylative insertion of a N-heterocycle at the C-terminal of peptides, yielding molecules that have potential medicinal applications. The key factors for the success of this reaction are the following: use of a photoredox catalyst of suitable redox potential to controllably generate α-aminoalkyl radicals, without overoxidation, and an acid cocatalyst to increase the electron deficiency of N-heteroarenes

Nickel-Catalyzed Regio- and Stereoselective Hydrocarboxylation of Alkynes with Formic Acid through Catalytic CO Recycling

By the combination of a Ni­(II) salt, a bisphosphine ligand, and a catalytic amount of carboxylic acid anhydride, atom-economic hydrocarboxylation of various alkynes with formic acid can be achieved with high selectivity and remarkable functional group compatibility, affording α,β-unsaturated carboxylic acids regio- and stereoselectively. Both terminal and internal alkynes are amenable substrates. A mechanism proceeding through carbon monoxide recycling in a catalytic amount is demonstrated to be crucial for the success of this transformation

Decarboxylative 1,4-Addition of α‑Oxocarboxylic Acids with Michael Acceptors Enabled by Photoredox Catalysis

Enabled by iridium photoredox catalysis, 2-oxo-2-(hetero)­arylacetic acids were decarboxylatively added to various Michael acceptors including α,β-unsaturated ester, ketone, amide, aldehyde, nitrile, and sulfone at room temperature. The reaction presents a new type of acyl Michael addition using stable and easily accessible carboxylic acid to formally generate acyl anion through photoredox-catalyzed radical decarboxylation

Irradiation-Induced Heck Reaction of Unactivated Alkyl Halides at Room Temperature

The palladium-catalyzed Mizoroki–Heck reaction is arguably one of the most significant carbon–carbon bond-construction reactions to be discovered in the last 50 years, with a tremendous number of applications in the production of chemicals. This Nobel-Prize-winning transformation has yet to overcome the obstacle of its general application in a range of alkyl electrophiles, especially tertiary alkyl halides that possess eliminable β-hydrogen atoms. Whereas most palladium-catalyzed cross-coupling reactions utilize the ground-state reactivity of palladium complexes under thermal conditions and generally apply a single ligand system, we report that the palladium-catalyzed Heck reaction proceeds smoothly at room temperature with a variety of tertiary, secondary, and primary alkyl bromides upon irradiation with blue light-emitting diodes in the presence of a dual phosphine ligand system. We rationalize that this unprecedented transformation is achieved by utilizing the photoexcited-state reactivity of the palladium complex to enhance oxidative addition and suppress undesired β-hydride elimination

<i>Cis</i>-Selective Decarboxylative Alkenylation of Aliphatic Carboxylic Acids with Vinyl Arenes Enabled by Photoredox/Palladium/Uphill Triple Catalysis

An iridium photoredox catalyst in combination with phenanthroline-supported palladium catalyst catalyzes decarboxylative alkenylation of tertiary and secondary aliphatic carboxylic acids with vinyl arenes to deliver β-alkylated styrenes with <i>Z</i>-selectivity. A broad scope of aliphatic carboxylic acids, including amino acids, exhibit as amenable substrates, and external oxidant is not required. The reaction proceeds by synergistic utilization of both energy-transfer and electron-transfer reactivity of iridium photoredox catalyst merging with palladium-catalyzed hydride elimination and insertion

Isonicotinate Ester Catalyzed Decarboxylative Borylation of (Hetero)Aryl and Alkenyl Carboxylic Acids through <i>N</i>‑Hydroxyphthalimide Esters

Decarboxylative borylation of aryl and alkenyl carboxylic acids with bis­(pinacolato)­diboron was achieved through <i>N</i>-hydroxyphthalimide esters using <i>tert</i>-butyl isonicotinate as a catalyst under base-free conditions. A variety of aryl carboxylic acids possessing different functional groups and electronic properties can be smoothly converted to aryl boronate esters, including those that are difficult to decarboxylate under transition-metal catalysis, offering a new method enabling use of carboxylic acid as building blocks in organic synthesis. Mechanistic analysis suggests the reaction proceeds through coupling of a transient aryl radical generated by radical decarboxylation with a pyridine-stabilized persistent boryl radical. Activation of redox active esters may proceed via an intramolecular single-electron-transfer (SET) process through a pyridine–diboron–phthalimide adduct and accounts for the base-free reaction conditions

<i>Cis</i>-Selective Decarboxylative Alkenylation of Aliphatic Carboxylic Acids with Vinyl Arenes Enabled by Photoredox/Palladium/Uphill Triple Catalysis

An iridium photoredox catalyst in combination with phenanthroline-supported palladium catalyst catalyzes decarboxylative alkenylation of tertiary and secondary aliphatic carboxylic acids with vinyl arenes to deliver β-alkylated styrenes with <i>Z</i>-selectivity. A broad scope of aliphatic carboxylic acids, including amino acids, exhibit as amenable substrates, and external oxidant is not required. The reaction proceeds by synergistic utilization of both energy-transfer and electron-transfer reactivity of iridium photoredox catalyst merging with palladium-catalyzed hydride elimination and insertion

Rh(III)-Catalyzed C–H Activation with Allenes To Synthesize Conjugated Olefins

Rh^III-catalyzed C–H activation with allenes produces highly unsaturated conjugated olefins. The reaction is applicable to both olefin and arene C­(sp²)–H and is compatible with a variety of functional groups. The products can be further transformed into other important skeletons through Diels–Alder reaction and intramolecular transesterification

Rhodium-Catalyzed Directed C–H Cyanation of Arenes with <i>N-</i>Cyano‑<i>N</i>‑phenyl‑<i>p</i>‑toluenesulfonamide

A Rh-catalyzed directed C–H cyanation reaction was developed for the first time as a practical method for the synthesis of aromatic nitriles. <i>N</i>-Cyano-<i>N</i>-phenyl-<i>p</i>-toluenesulfonamide, a user-friendly cyanation reagent, was used in the transformation. Many different directing groups can be used in this C–H cyanation process, and the reaction tolerates a variety of synthetically important functional groups

Rhodium-Catalyzed Directed C–H Cyanation of Arenes with <i>N-</i>Cyano‑<i>N</i>‑phenyl‑<i>p</i>‑toluenesulfonamide

A Rh-catalyzed directed C–H cyanation reaction was developed for the first time as a practical method for the synthesis of aromatic nitriles. <i>N</i>-Cyano-<i>N</i>-phenyl-<i>p</i>-toluenesulfonamide, a user-friendly cyanation reagent, was used in the transformation. Many different directing groups can be used in this C–H cyanation process, and the reaction tolerates a variety of synthetically important functional groups