Palladium Carbene Migratory Insertion Research Articles

Palladium-Catalyzed Cyclization Coupling with Cyclobutanone-Derived N-Tosylhydrazones: Synthesis of Benzofuran-3-Cyclobutylidenes and Spirocyclobutanes

A palladium-catalyzed cyclization coupling of iodoarene-tethered alkynes with cyclobutanone-derived N-tosylhydrazones is reported, providing a convenient and efficient approach to benzofuran-3-cyclobutylidenes. On this basis, spirocyclobutanes can be generated smoothly in an efficient cascade manner by the addition of dienophiles. Good yields and scalability are demonstrated. Sequential intramolecular carbopalladation, palladium-carbene migratory insertion, δ-hydride elimination, and cycloaddition processes are involved.

Cross-Coupling of Cyclobutenone N-Tosylhydrazones with Organohalides: Access to Conjugated Enynes and Enallenes via a Strained Allylpalladium Intermediate

A palladium-catalyzed cross-coupling reaction of cyclobutenone N-tosylhadrazones with organohalides is disclosed. The protocol involves the generation of a strained allylpalladium intermediate from readily available starting materials through palladium carbene migratory insertion, which undergoes electrocyclic ring opening and β-hydride elimination for the production of conjugated enynes and enallenes. The broad substrate scope, good to excellent yields, and tunable product diversity make the protocol potentially useful in organic synthesis.

Palladium-Catalyzed Three-Component Coupling Reaction via Benzylpalladium Intermediate.

Transition-metal catalyzed multi-component reactions have captured the attention of researchers in organic synthesis and drug synthesis due to their advantages of simple operation, easy availability of raw materials and without separation of intermediates. Among the multi-component reactions, the three-component processes have been developed into effective organic procedures. This personal account reviews our and other group's studies on the development of three-component coupling reaction for the rapid construction of two new chemical bonds simultaneously via benzylpalladium intermediates. Catalyst-switched three-component reactions of benzyl halides, activated olefins, and allyltributylstannane were successfully conducted to produce the corresponding benzylallylation products. Activation and conversion of carbon monoxide and carbon dioxide via π-benzylpalladium intermediates provide access to a wide range of unsaturated ketones and esters with excellent functional group tolerance. Meanwhile, other methods to produce benzylpalladium intermediates, including Heck insertion of alkenes into arylpalladium complexes, the oxidative addition of benzyl carbonate to palladium complexes and palladium-carbene migratory insertion, were also highlighted.

Pd-Catalyzed Coupling of Thioamides with N-Tosylhydrazones/Trapping by Esters Cascade Reaction.

N,N-Disubstituted thioamides coupled with N-tosylhydrazones under Pd(TFA)2/tBuXPhos catalyst and NaOtBu, and the intermediates from palladium carbene migratory insertion containing β-hydrogen were trapped by intramolecular esters activated by BF3·Et2O instead of undergoing β-H elimination, providing polyfunctional thiophen-3(2H)-ones with sulfur-containing tetrasubstituted carbon centers in moderate to good yields. The reaction features the formation of three bonds in a single operation, odorless, safe, and easily available substrates, wide substrate scope, and excellent functional group tolerance.

Easy access to medium-sized lactones through metal carbene migratory insertion enabled 1,4-palladium shift

Reactions that efficiently construct medium-sized lactones are significant, as they overcome the unfavorable entropic factor and transannular interactions for ring closure, and the lactones produced are common structural motifs recurring in many biologically active compounds. Herein, we describe a valuable strategy for medium-sized lactone synthesis by accomplishing site-selective C–H bond functionalization via a palladium carbene migratory insertion enabled 1,4-palladium shift. The overall process achieves the formal dimerization of two readily available benzaldehyde derivatives, providing value-added products medium-sized lactones. Our method is amenable to late-stage modification of approved drugs and other complex molecules. Mechanistic studies including deuterium-labeling experiments and DFT calculation shed light on the reaction pathways.

Palladium-Catalyzed Oxidative Cross-Coupling of Conjugated Enynones with Allylarenes: Synthesis of Furyl-Substituted 1,3-Dienes.

A new method for the synthesis of furyl-substituted 1,3-dienes via palladium-catalyzed oxidative cross-coupling of conjugated enynones with allylarenes is developed. This reaction shows broad substrate scope and good functional group tolerance. Palladium carbene migratory insertion is proposed as the key step for this transformation with conjugated enynones serving as the carbene precursors.

Palladium-Catalyzed Annulation via Acyl C–H Bond Activation

Palladium-catalyzed annulation of ortho-bromobenzaldehydes with aryl diazoesters is achieved via a sequence of palladium carbene migratory insertion, acyl C–H bond activation and reductive elimination of a seven-membered palladacyclic intermediate. A variety of isocoumarin derivatives were furnished in a straightforward manner.

Palladium-catalyzed olefination of aryl/alkyl halides with trimethylsilyldiazomethane via carbene migratory insertion.

The direct olefination of aryl/alkyl halides with trimethylsilyldiazomethane (TMSD) as a C1- or C2-unit was achieved successfully via a metal carbene migratory insertion process, which offered a new access to afford (E)-vinyl silanes and (E)-silyl-substituted α,β-unsaturated amides in good yields and high chemoselectivity.

Palladium-Catalyzed Oxidative Cross-Coupling of Conjugated Enynones with Organoboronic Acids.

A palladium-catalyzed oxidative cross-coupling reaction of conjugated enynones with organoboronic acids is developed. This reaction provides an efficient methodology for the synthesis of functionalized furan derivatives, including 2-alkenylfurans and furan-substituted 1,3-dienes. Palladium-carbene migratory insertion is proposed as the key step in these transformations. Notably, the β-hydride elimination process occurs in a stereoselective manner, resulting in the formation of double bonds with high (E)-selectivity.

ChemInform Abstract: Palladium‐Catalyzed Three‐Component Reaction of N‐Tosylhydrazone, Norbornene and Aryl Halide.

A palladium-catalyzed three-component reaction of N-tosylhydrazone, norbornene and aryl halide has been demonstrated. In this reaction, an intermolecular Heck-type reaction occurs, which is followed by the alkyl palladium carbene migratory insertion process. This transformation provides an efficient and convenient methodology for the double functionalization of norbornene with good to excellent yields.

Oxidative Cross‐Coupling of Allenyl Ketones and Organoboronic Acids: Expeditious Synthesis of Highly Substituted Furans

Allenyl ketones are employed as coupling partners in palladium-catalyzed oxidative cross-coupling reactions with organoboronic acids. This reaction constitutes an efficient methodology for the synthesis of highly substituted furan derivatives. Palladium-carbene migratory insertion is proposed as the key step in this transformation.

ChemInform Abstract: Palladium‐Catalyzed Carbene Migratory Insertion Using Conjugated Ene—Yne—Ketones as Carbene Precursors.

AbstractThe reaction is proposed to proceed via oxidative addition, alkyne activation—cyclization, palladium carbene migratory insertion and β—hydride elimination followed by catalyst regeneration.

Palladium-catalyzed three-component reaction of N-tosylhydrazone, norbornene and aryl halide.

A palladium-catalyzed three-component reaction of N-tosylhydrazone, norbornene and aryl halide has been demonstrated. In this reaction, an intermolecular Heck-type reaction occurs, which is followed by the alkyl palladium carbene migratory insertion process. This transformation provides an efficient and convenient methodology for the double functionalization of norbornene with good to excellent yields.

Palladium-Catalyzed Insertion of N-tosylhydrazones and Trapping with Carbon Nucleophiles

A Pd-catalyzed three-component cross-coupling reaction of vinyl iodide, N-tosylhydrazone, and carbon nucleophiles is reported, and a one-pot procedure is also developed. The cross-coupling is proposed to proceed through a palladium-carbene migratory insertion, carbopalladation other than classic palladium-carbene migratory insertion, and β-H elimination. Moreover, the reaction proceeds under mild conditions and with high stereoselectivity.

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 Three‐Component Reaction of Allenes, Aryl Iodides, and Diazo Compounds: Approach to 1,3‐Dienes

'Diene' to know: The title reaction leads to the formation of 1,3-dienes in high yields (see scheme). The reaction also proceeds with the use of N-tosylhydrazone substrates. Carbopalladation to the allene and palladium carbene migratory insertion are proposed to play the key role in this transformation.

ChemInform Abstract: Carbon—Carbon Bond Formation: Palladium‐Catalyzed Oxidative Cross‐Coupling of N‐Tosylhydrazones with Allylic Alcohols.

In the zone: Pd-catalyzed oxidative cross-coupling of N-tosylhydrazones with allylic alcohols leads to CC bond formation. A palladium-carbene migratory insertion is proposed to play the key role in this transformation. The reaction proceeds with readily available starting materials to afford substituted alkenes in a highly stereoselective manner.

Carbon–Carbon Bond Formation: Palladium‐Catalyzed Oxidative Cross‐Coupling of N‐Tosylhydrazones with Allylic Alcohols

In the zone: Pd-catalyzed oxidative cross-coupling of N-tosylhydrazones with allylic alcohols leads to CC bond formation. A palladium-carbene migratory insertion is proposed to play the key role in this transformation. The reaction proceeds with readily available starting materials to afford substituted alkenes in a highly stereoselective manner.