Palladium-Catalyzed Negishi Cross-Coupling Research Articles

Concise Asymmetric Total Syntheses of (+)-Dihydropleurotinic Acid and (-)-Pleurotin, Enabling Rapid Late-Stage Diversification.

(-)-Pleurotin (1) and (+)-dihydropleurotinic acid (2) are benzoquinone meroterpenoids isolated from fungal sources with powerful antitumor and antibiotic activities. Concise asymmetric total syntheses of the stereochemically pure (+)-dihydropleurotinic acid (2) and (-)-pleurotin (1) from the chiral pool (R)-Roche ester-derived vinyl bromide 7 have been achieved in 12 and 13 longest linear steps, respectively. The key transformations feature a Michael addition/alkylation cascade reaction to forge three contiguous stereocenters matched with the natural products, a PtO2-catalyzed stereoselective reduction of olefin to generate the correct stereocenter at C3, a palladium-catalyzed Negishi cross-coupling between triflate and zinc reagent to introduce the redox-sensitive para-quinone moiety, and a hydroboration/copper-catalyzed carboxylation sequence to incorporate the vital carboxyl group. Thus, the highly efficient and scalable preparation of pleurotin's pentacyclic skeleton enables the late-stage diversification, affording otherwise unavailable pleurotin analogs with significantly improved antiproliferative activities against the thioredoxin reductase (TrxR) overexpressed human breast cancer cell lines relative to the natural product pleurotin (1).

Expanding the functional group tolerance of cross-coupling in 1,2-dihydro-1,2-azaborines: Installation of alkyl, alkenyl, aryl, and heteroaryl substituents while maintaining a B−H bond

Palladium-catalyzed Negishi cross-coupling of 3-bromo-1-(tert-butyldimethylsilyl)-1,2-dihydro-1,2-azaborine while maintaining the B−H functionality has been demonstrated. 17 examples, including dialkylzinc, alkyl-, alkenyl-, aryl-, as well as nitrogen-, sulfur-, and oxygen-containing heteroaryl-zinc halide reagents have been coupled to generate new C(3) substituted 1,2-azaborines in moderate to excellent yields.

Palladium-Catalyzed Cross-Coupling of Ethyl Bromodifluoroacetate with Aryl Bromides or Triflates and Cross-Coupling of Ethyl Bromofluoroacetate with Aryl Iodides.

A palladium-catalyzed Negishi cross-coupling reaction of ethyl bromodifluoroacetate with aryl bromides or aryl triflates to construct C(sp2)-CF2 bonds is described. The reaction was conducted under mild reaction conditions, and no preparation of organozinc reagents is required. This is the first report encompassing the conversion of aryl triflates into products containing C-CF2 bonds. In addition, the construction of C(sp2)-CHF bonds was achieved under mild conditions via a cross-coupling of aryl iodides with ethyl bromofluoroacetate.

Palladium-Catalyzed Negishi Cross-Coupling Reaction of Aryl Halides with (Difluoromethyl)zinc Reagent.

The palladium-catalyzed Negishi cross-coupling reaction of aryl iodides and bromides with (difluoromethyl)zinc reagent bearing a diamine such as TMEDA is achieved to provide the difluoromethylated aromatic compounds in good to excellent yields. The advantages of (difluoromethyl)zinc reagent are that (1) the derivatives, which possess different stability and reactivity, can be readily prepared via ligand screening and (2) transmetalation of a difluoromethyl group from the zinc reagent to palladium catalyst efficiently proceeds without an activator.

ChemInform Abstract: Heteroarylation of Azine N‐Oxides.

AbstractThe process is highly efficient for the preparation of various heterobiaryl structures.

Heteroarylation of Azine N-Oxides

Azine N-oxides undergo highly regioselective metalation with TMPZnCl·LiCl under mild conditions. A palladium-catalyzed Negishi cross-coupling reaction of the resulting organozinc species with heteroaromatic bromides provides heterobiaryls specifically oxidized at one nitrogen position in up to 95% yield.

Palladium-catalyzed Negishi α-arylation of alkylsulfones

A general, mild catalytic system for α-monoarylation of various alkyl sulfones is described that utilizes palladium-catalyzed Negishi cross-coupling approach.

A Facil and Efficient Synthesis of Mono- and Bis-functionalized meso-Substituted Porphyrins via Palladium-Catalyzed Negishi Cross-Coupling

A series of mono- and bis-functionalized meso-substituted porphyrins bearing chemically reactive functional groups such as -COOR, -Cl, and -CN in the alkyl substituents at the meso positions were efficiently synthesized by the reactions of meso-brominated precursors with alkylzinc reagents via palladium-catalyzed Negishi cross-coupling.

Palladium-Catalyzed Negishi Cross-Coupling of Arylzinc Reagents with Functionalized Vinylic Tellurides

The Negishi cross-coupling reaction of arylzinc chlorides and bromides with functionalized vinylic tellurides in the presence of a catalytic amount of PdCl 2 in THF at room temperature is described. This cross-coupling reaction is general and permits the synthesis of functionalized substituted alkenes in good yields and high stereoselectivity.

Palladium-Catalyzed Negishi Cross-Coupling Reactions of Unactivated Alkyl Iodides, Bromides, Chlorides, and Tosylates.

For Abstract see ChemInform Abstract in Full Text.

Preparation of 5-Heteroaryl Substituted 1-(4-Fluorophenyl)-1H-indoles via Palladium-Catalyzed Negishi and Stille Cross-Coupling Reactions

Palladium-catalyzed Negishi cross-coupling of 5-1-(4-fluorophenyl)indolylzinc chloride with N-methyl-halopyrazoles, bromopyridines and bromopyrimidines in gram scale gave the corresponding cross-coupled products in 38-85% yield.

The first general method for palladium-catalyzed Negishi cross-coupling of aryl and vinyl chlorides: use of commercially available Pd(P(t-Bu)(3))(2) as a catalyst.

With a single protocol, commercially available Pd(P(t-Bu)(3))(2) can effect the Negishi cross-coupling of a wide range of aryl and vinyl chlorides with aryl- and alkylzinc reagents. The process tolerates nitro groups, and it efficiently generates sterically hindered biaryls. In addition, a high turnover number (>3000) can be achieved.

Preparation of 2- and 5-Aryl Substituted Thiazoles via Palladium-Catalyzed Negishi Cross-Coupling

Preparation of 2- and 5-Aryl Substituted Thiazoles via Palladium-Catalyzed Negishi Cross-Coupling