Palladium-catalyzed Isocyanide Insertion Research Articles

Direct access to thiomethyl/selenomethyl-substituted pyrazoles by combining isocyanide insertion into the inert C(sp)–S bond and intermolecular cyclization

A strategy for preparing a series of thiomethyl/selenomethyl substituted pyrazoles through palladium-catalyzed isocyanide insertion into the C(sp)–S bond, followed by TMSN3-involved CuI/Sc(OTf)3 catalyzed intermolecular cyclization was reported.

Synthesis of Polysubstituted Pyrimidines through Palladium-Catalyzed Isocyanide Insertion to 2H-Azirines.

The domino process of the palladium-catalyzed coupling reaction of isocyanides with 2H-azirine provides various tetrasubstituted pyrimidines via one C-C bond and two C-N bond formations with satisfactory yields. The title compounds are obtained with good functional group tolerance, high atom economy, and broad substrate scopes.

Recent Advances in Palladium-Catalyzed Isocyanide Insertions.

Isocyanides have long been known as versatile chemical reagents in organic synthesis. Their ambivalent nature also allows them to function as a CO-substitute in palladium-catalyzed cross couplings. Over the past decades, isocyanides have emerged as practical and versatile C1 building blocks, whose inherent N-substitution allows for the rapid incorporation of nitrogeneous fragments in a wide variety of products. Recent developments in palladium catalyzed isocyanide insertion reactions have significantly expanded the scope and applicability of these imidoylative cross-couplings. This review highlights the advances made in this field over the past eight years.

C(sp2)-H Functionalization of Imidazole at the C2- and C4-Position via Palladium-Catalyzed Isocyanide Insertion Leading to Indeno[1,2-d]imidazole and Imidazo[1,2-a]indole Derivatives.

An efficient strategy for the construction of fused imidazole derivatives through a palladium-catalyzed isocyanide insertion reaction has been accomplished. The methodology provides an operationally simple and versatile route for the synthesis of indeno[1,2-d]imidazole and imidazo[1,2-a]indole skeletons which are rarely reported. The key features of the protocol are construction of sequential C-C/C-C/C-N bonds via C(sp2)-H functionalization of imidazole at the C2- and C4-position, respectively. The compounds can be synthesized with diverse scaffolds, easily accessible starting materials, and moderate to good yields.

Palladium-catalyzed synthesis of 5-amino-1,2,4-oxadiazoles via isocyanide insertion.

A convenient and efficient palladium-catalyzed approach has been developed for the synthesis of 5-amino-1,2,4-oxadiazoles from amidoximes and isocyanides. Various 5-amino-1,2,4-oxadiazoles were obtained in moderate to high yields under mild conditions. The key to the success of this strategy involves new C-N bond and C-O bond formation via palladium-catalyzed isocyanide insertion.

Base Metal Catalyzed Isocyanide Insertions.

Isocyanides are diverse C1 building blocks considering their potential to react with nucleophiles, electrophiles, and radicals. Therefore, perhaps not surprisingly, isocyanides are highly valuable as inputs for multicomponent reactions (MCRs) and other one-pot cascade processes. In the field of organometallic chemistry, isocyanides typically serve as ligands for transition metals. The coordination of isocyanides to metal centers alters the electronic distribution of the isocyano moiety, and reaction pathways can therefore be accessed that are not possible in the absence of the metal. The tunable reactivity of the isocyanide functional group by transition metals has evolved into numerous useful applications. Especially palladium-catalyzed isocyanide insertion processes have emerged as powerful reactions in the past decade. However, reports on the use of earth-abundant and cheap base metals in these types of transformations are scarce and have received far less attention. In this Minireview, we focus on these emerging base metal catalyzed reactions and highlight their potential in synthetic organic chemistry. Although mechanistic studies are still scarce, we discuss distinct proposed catalytic cycles and categorize the literature according to 1) the (hetero)atom bound to and 2) the type of bonding with the transition metal in which the (formal) insertion occurs.

Synthesis of iminoisoindolinones via a cascade of the three-component Ugi reaction, palladium catalyzed isocyanide insertion, hydroxylation and an unexpected rearrangement reaction.

A robust ligand-free palladium-catalyzed cascade reaction for the synthesis of diversely substituted iminoisoindolinones has been developed. The cascade reaction involves isocyanide insertion into Ugi-3CR adducts, accompanied by unexpected hydroxylation and rearrangement.

ChemInform Abstract: Synthesis of 3‐Aryl‐2‐aminoquinolines: Palladium‐Catalyzed Cascade Reactions of gem‐Dibromovinylanilines with tert‐Butyl Isocyanide and Arylboronic Acids.

A three-component cascade reaction involving gem-dibromovinylanilines, tert-butyl isocyanide and arylboronic acids for the efficient synthesis of 3-aryl-2-aminoquinolines has been developed. The reaction proceeds through palladium-catalyzed isocyanide insertion, intramolecular cyclization of gem-dibromovinylanilines followed by Suzuki coupling with arylboronic acids, and the corresponding products were obtained in good to excellent isolated yields.

Facile synthesis of 2-amino-3-bromoquinolines by palladium-catalyzed isocyanide insertion and cyclization of gem-dibromovinylanilines

A novel and efficient synthesis of 2-amino-3-bromoquinolines through palladium-catalyzed isocyanide insertion followed by intramolecular cyclization of gem-dibromovinylanilines was developed.

Synthesis of Pyridopyrimidines by Palladium-Catalyzed Isocyanide Insertion

A new synthetic approach to 4-aminopyrido[2,3-d]pyrimidines and 4-aminopyrido[3,2-d]pyrimidines based on palladium-catalyzed reaction of isocyanides with readily available N-(bromopyridyl)amidines is reported. The target heterocycles were obtained in generally good to excellent yield. For the two regioisomeric pyrimidopyrimidines, we compared our approach involving oxidative addition with the analogous C–H activation protocol because both methods have been reported for the synthesis of 4-aminoquinazolines. We found that the C–H activation protocol does not allow one to obtain the target pyridopyrimidines, but the imidoylative cross-coupling protocol provided a new entry to the synthesis of these medicinally important scaffolds.

Synthesis of 3-Acyl-2-arylindole via Palladium-catalyzed Isocyanide Insertion and Oxypalladation of Alkyne

Synthesis of 3-Acyl-2-arylindole via Palladium-catalyzed Isocyanide Insertion and Oxypalladation of Alkyne

Synthesis of 3-Acyl-2-arylindole via Palladium-catalyzed Isocyanide Insertion and Oxypalladation of Alkyne

The synthesis of 3-acyl-2-arylindole derivatives was performed through palladium-catalyzed isocyanide insertion and oxypalladation of an alkyne. As a result of the introduction of internal nucleophiles, domino cyclization was also achieved for the synthesis of several tetracyclic indole derivatives. Imidoylpalladium generated by isocyanide insertion is a key intermediate in these reactions.

Multicomponent Synthesis of 4-Aminophthalazin-1(2H)-ones by Palladium-Catalyzed Isocyanide Insertion

4-Aminophthalazin-1(2H)-ones (APOs) are underexplored heterocyclic compounds with promising and diverse biological activities. The classical synthesis of these compounds is tedious and does not allow the regioselective introduction of substituents. Here, we present our full studies on the Pd-catalyzed cross-coupling of substituted o-(pseudo)halobenzoates and hydrazines with isocyanide insertion allowing straightforward access to diversely substituted APOs. We illustrate the advantages of this method compared to other approaches and describe solutions for the limitations we encountered. In addition, we have developed efficient diversifications of this heterocyclic scaffold that allow access to more diverse APOs as well as novel heterocyclic scaffolds.

A Practical, Ligand-Free, Palladium-Catalyzed Isocyanide Insertion Reaction for the Construction of Novel Ring-Fused Quinazolinones

A high-yielding, ligand-free, palladium-catalyzed isocyanide insertion reaction for the synthesis of phthalazino[1,2-<i>b</i>]quinazolinones from the readily obtainable quinazolinones has been developed. Easily handled and relatively low-cost palladium(II) acetate was used as the catalyst, without an additional ligand. Preparation of the quinazolinones involved the cascade reaction of isatoic anhydrides, phenylhydrazines and 2-bromobenzaldehyde catalyzed by <i>p</i>-toluenesulfonic acid in one pot. This novel protocol may be applicable for the synthesis of other important ring-fused heterocyclic compounds.

A palladium-catalyzed three-component reaction for the preparation of quinazolin-4(3H)-imines

A novel and efficient route for the preparation of quinazolin-4(3H)-imines via a palladium-catalyzed three-component reaction of carbodiimide, isocyanide, and nucleophile is described. The palladium-catalyzed isocyanide insertion is believed to be the key step during the reaction process.