Palladium-Catalyzed Carbene Research Articles

Palladium-Catalyzed Carbene Migratory Insertion/Carbonylation Cascade Reaction: Synthesis of 2-Indolones with a C3 All-Carbon Quaternary Center.

An attractive palladium-catalyzed three-component reaction of ortho-amino aryl diazo esters, allyl carboxylates, and carbon monoxide (CO) has been developed. This catalytic system rendered domino carbene migratory insertion and carbonylation. Remarkably, 2-indolones 3 with a C3 all-carbon quaternary center can be selectively obtained in good to excellent yields via one-pot synthesis, in which two different C-C bonds and one C-N bond were formed in a straightforward manner.

Palladium-catalyzed carbene coupling polymerization: synthesis of E-poly(arylene vinylene)s.

The Pd-catalyzed carbene coupling reaction of N-tosylhydrazones and benzyl bromides has been developed into a polymerization process for the first time, providing an efficient method for the synthesis of poly(arylene vinylene)s (PAVs). This method affords PAVs bearing E-vinylene units predominantly. It can also introduce a CF3 group on each vinylene carbon atom in the polymer main chain. The polymerization has a broad scope and the resultant polymers exhibit interesting optical properties and good thermal stabilities.

Palladium-Catalyzed Enantioselective Carbene Insertion into Carbon-Silicon Bonds of Silacyclobutanes.

We report herein a highly efficient palladium-catalyzed carbene insertion into strained Si-C bonds with excellent enantioselectivity, which provides a rapid and distinct method to access silacyclopentanes with a three- or four-substituted stereocenter asymmetrically. Mechanistic studies using hybrid density functional theory suggest a catalytic cycle involving oxidative addition, carbene migratory insertion, and reductive elimination. In addition, roles of the chiral ligands in controlling the reaction enantioselectivity are also elucidated.

Synthesis of Alkenylboronates from N-Tosylhydrazones through Palladium-Catalyzed Carbene Migratory Insertion.

The palladium-catalyzed oxidative borylation reaction of N-tosylhydrazones has been developed. The reaction features mild conditions, broad substrate scope, and good functional group tolerance. It thus represents a highly efficient and practical method for the synthesis of di-, tri-, and tetrasubstituted alkenylboronates from readily available N-tosylhydrazones. One-pot Suzuki coupling and other transformations highlight the synthetic utility of the approach. DFT calculations have revealed that palladium-carbene formation and subsequent boryl migratory insertion are the key steps in the catalytic cycle. The high stereoselectivity observed in the formation of trisubstituted alkenylboronates has been explained by distortion-interaction analysis and NBO analysis.

A modular strategy for the synthesis of marine originated meroterpenoid-type natural products.

A modular strategy for meroterpenoid-type marine natural products has been developed from commercially available (+)-sclareolide using a palladium-catalyzed tandem carbene migratory insertion as one of the key steps. Its applicability is showcased by the formal synthesis of (-)-pelorol and 9-epi-pelorol and the concise total synthesis of (+)-yahazunone and (+)-yahazunol. It is worth noting that the formal synthesis of (-)-pelorol and 9-epi-pelorol was achieved by controlling the reaction sequence of hydrogenation and cyclization.

Recent Advances in Palladium-Catalyzed Bridging C–H Activation by Using Alkenes, Alkynes or Diazo Compounds as Bridging Reagents

AbstractTransition-metal-catalyzed direct inert C–H bond functionalization has attracted much attention over the past decades. However, because of the high strain energy of the suspected palladacycle generated via C–H bond palladation, direct functionalization of a C–H bond less than a three-bond distance from a catalyst center is highly challenging. In this short review, we summarize the advances on palladium-catalyzed bridging C–H activation, in which an inert proximal C–H bond palladation is promoted by the elementary step of migratory insertion of an alkene, an alkyne or a metal carbene intermediate.1 Introduction2 Palladium-Catalyzed Alkene Bridging C–H Activation2.1 Intramolecular Reactions2.2 Intermolecular Reactions3 Palladium-Catalyzed Alkyne Bridging C–H Activation3.1 Intermolecular Reactions3.2 Intramolecular Reactions4 Palladium-Catalyzed Carbene Bridging C–H Activation5 Conclusion and Outlook

Synthesis of Trifluoromethylated Tetrasubstituted Allenes via Palladium-Catalyzed Carbene Transfer Reaction.

Herein, we report on the palladium-catalyzed synthesis of trifluoromethylated, tetrasubstituted allenes from vinyl bromides and trifluoromethylated diazoalkanes in good to excellent yield. This reaction proceeds via oxidative addition of a Pd(0) complex with vinyl bromide. Subsequent base-promoted reductive elimination generates the allene. This methodology provides an efficient strategy even on gram scale to valuable trifluoromethylated, tetrasubstituted allenes under mild reaction conditions. The allene products can be used in acid catalyzed cyclization reactions to give trifluoromethylated indene products.

Total Synthesis of (±)-Brazilin Using [4 + 1] Palladium-Catalyzed Carbenylative Annulation.

Palladium-catalyzed carbene insertion was utilized in a formal synthesis of (±)-picropodophyllone and a total synthesis of (±)-brazilin. All prior syntheses of brazilin have involved a Friedel-Crafts alkylation in the key carbon-carbon bond forming events. The palladium-catalyzed [4 + 1] reaction generates a 1-arylindane with all of the functionalities needed for formation of the indano[2,1-c]chroman ring system of brazilin. The synthesis of (±)-brazilin was achieved in 11 steps (longest linear sequence) with an overall 11% yield.

Palladium-catalyzed carbene coupling of N-tosylhydrazones and arylbromides to synthesize cross-conjugated polymers

Palladium-catalyzed cross-coupling reactions of N-tosylhydrazones and arylbromides have been applied for the first time in the synthesis of cross-conjugated polymers, namely poly(arylene-1,1-vinylidene)s (iso-PAVs).

Palladium-Catalyzed Carbene Migratory Insertion and Trapping with Sulfinic Acid Salts toward Allylic Sulfones.

Allylic sulfones were synthesized with excellent selectivity and good yield via Pd-catalyzed cross-coupling of vinyl iodide with N-tosylhydrazone. This process involves palladium carbene migratory insertion/trapping with sulfinic acid salts. For the previous Pd-catalyzed N-tosylhydrazone cross-coupling, sulfinic acid salt is generated as a byproduct. In this transformation, the diazo compound and the sulfinic acid salt, which are all generated from N-tosylhydrazone, were used as cross-coupling partner.

C[double bond, length as m-dash]N bond formation via palladium-catalyzed carbene insertion into N[double bond, length as m-dash]N bonds: inhibiting the general 1,2-migration process of ylide intermediates.

A new example of C[double bond, length as m-dash]N double bond formation in metal carbene insertion reactions is reported. Remarkably, the general 1,2-migration process of the corresponding ylide intermediates in X-H carbene insertion reactions that leads to C-X single bond formation is completely inhibited by replacing the H atom with a nitrogen atom. This palladium-catalyzed carbene insertion reaction with N[double bond, length as m-dash]N double bonds gave various N,N-disubstituted hydrazone products in high yields.

ChemInform Abstract: Palladium‐Catalyzed Intramolecular Carbene Insertion into C(sp3)—H Bonds.

AbstractA regioselective Pd‐catalyzed cyclization of α‐diazoesters to N‐arylpyrrolidines is developed.

Palladium-Catalyzed Intramolecular Carbene Insertion into C(sp(3) )-H Bonds.

A palladium-catalyzed carbene insertion into C(sp(3) )-H bonds leading to pyrrolidines was developed. The coupling reaction can be catalyzed by both Pd(0) and Pd(II) , is regioselective, and shows a broad functional group tolerance. This reaction is the first example of palladium-catalyzed C(sp(3) )-C(sp(3) ) bond assembly starting from diazocarbonyl compounds. DFT calculations revealed that this direct C(sp(3) )-H bond functionalization reaction involves an unprecedented concerted metalation-deprotonation step.

Enantioselective Palladium‐Catalyzed CH Functionalization of Indoles Using an Axially Chiral 2,2′‐Bipyridine Ligand

A palladium-catalyzed enantioselective CH functionalization of indoles was achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction protocol was also effective for asymmetric OH insertion reaction of phenols using α-aryl-α-diazoacetates. This represents the first successful application of bipyridine ligands with axial chirality in palladium-catalyzed carbene migratory insertion reactions.

Palladium-Catalyzed Carbene Migratory Insertion Using Conjugated Ene–Yne–Ketones as Carbene Precursors

Palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones lead to the formation of 2-alkenyl-substituted furans. This novel coupling reaction involves oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, β-hydride elimination, and catalyst regeneration. Palladium (2-furyl)carbene is proposed as the key intermediate, which is supported by DFT calculations. The palladium carbene character of the key intermediate is validated by three aspects, including bond lengths, Wiberg bond order indices, and molecular orbitals, by comparison to those reported for stable palladium carbene species. Computational studies also revealed that the rate-limiting step is ene-yne-ketone cyclization, which leads to the formation of the palladium (2-furyl)carbene, while the subsequent carbene migratory insertion is a facile process with a low energy barrier (<5 kcal/mol).

Palladium-catalyzed insertion of α,β-unsaturated N-tosylhydrazones and trapping with carbon nucleophiles

Palladium-catalyzed carbene migratory insertion-cyclization reactions were reported, delivering dihydronaphthalene and indene derivatives in moderate to good yields. A three-component cross-coupling was also developed. The reactions are easy to handle, under mild conditions and various functional groups are tolerated.

Palladium-Catalyzed Carbene Insertion and Trapping with Carbon Nucleophiles

Palladium catalysts are shown to catalyze the three-component coupling of vinyl halides, trimethylsilyldiazomethane, and stabilized carbon nucleophiles. The reaction is believed to proceed through a palladium-carbene intermediate LX(R)PdCHSiMe 3 that undergoes migration of the vinyl substituent to the electrophilic carbene center to generate an eta 3-allylpalladium intermediate. The allylpalladium intermediate is attacked by the carbon nucleophile to generate a vinylsilane product.

Cyclization Reactions Involving Palladium-Catalyzed Carbene Insertion into Aryl Halides

Palladium is shown to catalyze the insertion of trimethylsilylmethylene into aryl halides, leading to benzylpalladium intermediates that cyclize to give indenylsilanes through carbopalladation of pendant alkenes or allenes. Allylsilanes generated through these processes are susceptible to protodesilylation in situ.

Palladium-Catalyzed Carbene Insertion into Vinyl Halides and Trapping with Amines

Palladium is shown to catalyze the three-component coupling of vinyl halides, trimethylsilyldiazomethane, and amines to generate allylamines. The mechanism is believed to involve formation of an R-Pd=CHSiMe3 intermediate that undergoes migration of the vinyl ligand to the empty p-orbital of the carbene ligand. The resulting eta1-allylpalladium species forms an eta3-allylpalladium intermediate that is trapped by the amine nucleophile. Under the conditions tested, cyclic secondary amines and terminal vinyl iodides give the best results.

Palladium-catalyzed carbene insertion into benzyl bromides

Palladium can catalyze the insertion of ethyl diazoacetate into benzyl bromides. The key step in the catalytic cycle is the migratory insertion of a carbene, derived from ethyl diazoacetate, into a Pd–C bond.