Palladium‐Catalyzed Insertion of Isocyanides into the C−S Bonds of Heteroaryl Sulfides

Insertion of tert‐butyl isocyanide into the C(sp²)?S bonds of heteroaryl sulfides is catalyzed by a palladium diphosphine complex. Thioimidates generated through this reaction could be readily hydrolyzed under acidic conditions to yield the corresponding thioesters, which are of synthetic use. This insertion is useful because starting heteroaryl sulfides were readily prepared by either conventional ways or through sulfur‐specific extended Pummerer reactions.     

Palladium‐Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

Free radical reactions for heterocycle synthesis. Part 6: 2-Bromobenzoic acids as building blocks in the construction of nitrogen heterocycles

A general method to construct a variety of nitrogen heterocycles is introduced. 2-Bromobenzoic acids or acid chlorides are used as the common building blocks to couple with appropriate nitrogen-containing compounds. Sequential aryl radical cyclizations including conjugate additions, spirocyclizations, homolytic and ipso aromatic substitutions, and 1,5-hydrogen atom transfers are employed to prepare tri- and tetracyclic isoindolinones, benzolactams, isoquinolinones, azabenzoisocoumarins, and bridged-azabicyclic compounds.     

Oxime radical promoted dioxygenation, oxyamination, and diamination of alkenes: synthesis of isoxazolines and cyclic nitrones

Up the tempo: The intramolecular addition of oxime radicals to C?C bonds was achieved by using DEAD and TEMPO to give 4,5-dihydroisoxazoles as a result of a C?O bond-forming, 5-exo-trig cyclization. γ,δ-Unsaturated ketoximes also reacted to afford cyclic nitrones through C?N bond formation. The reactions offer a metal-free approach for the vicinal difunctionalization of unactivated alkenes.     

Ugi/Aldol sequence: expeditious entry to several families of densely substituted nitrogen heterocycles

Complexity from simplicity: Nitrogen-containing heterocycles have been assembled by means of unprecedented domino processes designed to take advantage of diversity assembly using strategically decorated Ugi products. The aldol reaction is the second common denominator which enables sequences of up to five steps in one pot, thus producing unique molecular architectures in rapid fashion.     

Cyclization of Homopropargyl Chalcogenides by Copper(II) Salts: Selective Synthesis of 2,3‐Dihydroselenophenes, 3‐Arylselenophenes,and 3‐Haloselenophenes/thiophenes

Copper(II) halide mediated cyclization of homopropargyl chalcogenides gave three types of chalcogenophene derivatives. Selective product formation was achieved by controlling solvent, temperature, and atmosphere. By using CuBr₂ and 1,2‐dichloroethane at room temperature under ambient atmosphere, 4‐bromo dihydroselenophene derivatives were obtained, whereas CuBr₂ and 1,2‐dichloroethane at reflux gave selectively 2‐substituted selenophenes. When 1,2‐dichloroethane was replaced by dimethylacetamide, 3‐halo‐selenophenes were obtained exclusively. The versatility of chalcogenophenes was also studied by reaction of 3‐haloselenophenes with terminal alkynes under Sonogashira conditions affording the cross‐coupled products. In addition, the reaction of 3‐haloselenophenes with boronic acids gave the corresponding Suzuki‐type products in good yields.     

Silver-Catalyzed Three-Component 1,1-Aminoacylation of Homopropargylamines: α-Additions for Both Terminal Alkynes and Isocyanides

The reaction of secondary homopropargylamines, isocyanides, and water in the presence of a catalytic amount of silver acetate and subsequent purification by chromatography on silica gel afforded substituted proline amides in good to excellent yields. Primary homopropargylamines underwent a cyclizative Ugi–Joullié three-component reaction with isocyanides and carboxylic acids to afford functionalized N-acyl proline amides. High diastereoselectivity was observed in the synthesis of 4-alkoxy and 4,5-disubstituted proline derivatives. This work represents the first examples of a three-component cyclizative 1,1-aminoacylation of terminal alkynes.     

Synthesis of Substituted Pyrroles via Copper‐Catalyzed Cyclization of Ethyl Allenoates with Activated Isocyanides

A new method for the synthesis of di‐ and trisubstituted pyrroles via copper‐catalyzed cyclization of ethyl allenoates with activated isocyanides has been developed. In contrast to related annulation reactions previously reported, this new process features a skeletal rearrangement in which the aryl sulfonyl moiety, which functions as the electron‐withdrawing group in the α‐carbon of the isocyanide, was found to migrate to the γ‐carbon of the starting allenoate in the final product for the first time.