General Copper-Catalyzed Coupling of Alkyl-, Aryl-, and Alkynylaluminum Reagents with Organohalides.

We report the first example of a very general Cu-catalyzed cross-coupling of organoaluminum reagents with organohalides. The reactions proceed for the couplings of alkyl-, aryl-, and alkynylaluminum reagents with aryl and heteroaryl halides and vinyl bromides, affording the cross-coupled products in good to excellent yields. Both primary and secondary alkylaluminum reagents can be utilized as organometallic coupling partners. These reactions are not complicated by ß-hydride elimination, and as a result rearranged products are not observed with secondary alkylaluminum reagents even for couplings with heteroaryl halides under "ligand-free" conditions. Radical clock experiment with a radical probe and relative reactivity study of Ph3Al with two haloarenes, 1-bromonaphthalene and 4-chlorobenzonitrile, having two different redox potentials indicates that the reaction does not involve free aryl radicals and radical anions as intermediates. These results combined with the result of the Hammett plot obtained by reacting Ph3Al with iodoarenes containing p-H, p-Me, p-F, and p-CF3 substituents, which shows a linear curve (R(2) = 0.99) with a ρ value of +1.06, suggest that the current transformation follows an oxidative addition-reductive elimination pathway.

Ligand-Free Copper-Catalyzed Negishi Coupling of Alkyl-, Aryl-, and Alkynylzinc Reagents with Heteroaryl Iodides.

Reported herein is an unprecedented ligand-free copper-catalyzed cross-coupling of alkyl-, aryl-, and alkynylzinc reagents with heteroaryl iodides. The reaction proceeds at room temperature for the coupling of primary, secondary, and tertiary alkylzinc reagents with heteroaryl iodides without rearrangement. An elevated temperature (100 °C) is required for aryl-heteroaryl and alkynyl-heteroaryl couplings.

Copper-catalysed cross-coupling: an untapped potential.

Copper is emerging as a viable catalytic metal for cross-coupling reactions to construct carbon-carbon (C-C) bonds. Recent revelations that Cu-catalysts can execute with high efficacy the cross-couplings of a variety of organometallic reagents, including organomagnesium, organoboron, organosilicon, organoindium and organomanganese, with alkyl, aryl and heteroaryl halides clearly demonstrate the versatility of Cu-based catalytic systems in conducting these reactions. In addition, Cu-catalysts are exhibiting a unique reactivity pattern that allows ligandless cross-coupling for aryl-heteroaryl and heteroaryl-heteroaryl bond formation, a transformation that generally requires special custom-designed ligands with Pd-catalysts. This review summarises early discoveries and subsequent advancements made in the area of Cu-catalysed cross-couplings of organometallic reagents with organohalides to form C-C bonds.

Copper-catalysed cross-coupling of arylzirconium reagents with aryl and heteroaryl iodides.

An unprecedented Cu(I)-catalysed cross-coupling of arylzirconium reagents with aryl and heteroaryl iodides is reported. Mechanistic studies with a Cp2ZrAr2 complex revealed that Cp2Zr(Ar)(Cl) is the reactive species that undergoes transmetalation with (PN-1)CuI. In addition, experiments with radical probes indicated that the reaction proceeds via a non-radical pathway.

Copper-catalyzed coupling of triaryl- and trialkylindium reagents with aryl iodides and bromides through consecutive transmetalations.

An efficient copper(I)-catalyzed coupling of triaryl and trialkylindium reagents with aryl iodides and bromides is reported. The reaction proceeds at low catalyst loadings (2 mol%) and generally only requires 0.33 equivalents of the triorganoindium reagent with respect to the aryl halide as all three organic nucleophilic moieties of the reagent are transferred to the products through consecutive transmetalations. The reaction tolerates a variety of functional groups and sterically hindered substrates. Furthermore, preliminary mechanistic studies that entailed the synthesis and characterization of potential reaction intermediates offered a glimpse of the elementary steps that constitute the catalytic cycle.

Copper-catalyzed Suzuki-Miyaura coupling of arylboronate esters: transmetalation with (PN)CuF and identification of intermediates.

An efficient Cu(I)-catalyzed Suzuki-Miyaura reaction was developed for the coupling of aryl- and heteroarylboronate esters with aryl and heteroaryl iodides at low catalyst loadings (2 mol %). The reaction proceeds under ligand-free conditions for aryl-heteroaryl and heteroaryl-heteroaryl couplings. We also conducted the first detailed mechanistic studies by synthesizing [(PN-2)CuI]2, [(PN-2)CuF]2, and (PN-2)CuPh (PN-2 = o-(di-tert-butylphosphino)-N,N-dimethylaniline) and demonstrated that [(PN-2)CuF]2 is the species that undergoes transmetalation with arylboronate esters.

Copper-catalyzed Hiyama coupling of (hetero)aryltriethoxysilanes with (hetero)aryl iodides.

A Cu(I)-catalyzed Hiyama coupling was achieved, which proceeds in the absence of an ancillary ligand for aryl-heteroaryl and heteroaryl-heteroaryl couplings. A P,N-ligand is required to obtain the best product yields for aryl-aryl couplings. In addition to facilitating transmetalation, CsF is also found to function as a stabilizer of the [CuAr] species, potentially generated as an intermediate after transmetalation of aryltriethoxysilanes with Cu(I)-catalysts in the absence of ancillary ligands.

Synthesis and characterization of novel unnatural bichalcones.

Five bichalcones (5-1 ~ 5-4, 9) were prepared by the reaction of biphenyl-4,4'-dicarbaldehyde (4) and 4,4'-dioxybenzaldehyde (8) with the respective acetophenone analogs via Claisen-Schmidt condensation and were then fully identified by 1H-NMR, (13)C-NMR and mass analyses.

Inhibition of prostaglandin E2 production by synthetic wogonin analogs.

Effects of wogonin analogs on cyclooxygenase-2 (COX-2) catalyzed prostaglandin E2 production on lipopolysaccharide (LPS)-induced RAW 264.7 cells were investigated. Wogonin analogs were prepared via several different synthetic pathways. Among wogonin analogs tested, 8-halogeno and 8-nitro analogs showed strong inhibitory activities against COX-2 catalyzed PGE2 production from LPS-induced RAW 264.7 cells. Effect of wogonin was largely dependent on structural alteration of the 8-methoxy group.