Efficient ligand-free copper-catalyzed C-S cross-coupling of thiols with aryl iodides using KF/Al2O3 as base

We report a mild, convenient, environmentally friendly, and ligand-free synthetic protocol for the cross-coupling reaction of aryl iodides and thiols using 10 mol % CuI with KF/Al₂O₃ as the base, in DMF at 110 °C. Using this protocol, we have shown that a variety of aryl sulfides can be synthesized in excellent yields from readily available iodides and thiols.     

Improved synthesis of phenylethylamine derivatives by Negishi cross-coupling reactions

Trifluoroacetamido-protected β-aminoalkylzinc iodides undergo Negishi cross-coupling reaction with aryl iodides in moderate to excellent yields (42-84%) based on the corresponding trifluoroacetamido-protected β-aminoalkyl iodides, employing a catalyst prepared in situ from Pd₂(dba)₃ and SPhos (1:2 M ratio). In general, meta- and para-substituted aryl iodides give good results using relatively low levels of catalyst [0.25 mol % Pd₂(dba)₃], but more hindered ortho-substituted examples require higher catalyst loadings. The preparation of trifluoroacetamido-protected β-aminoalkyl iodides is straightforward, and the intermediates are significantly more stable than the corresponding Boc-protected derivatives.     

Facile synthesis of S-arylisothioureas via the S-arylation of arylthioureas with aryl iodides in water

An environmentally benign, simple and highly efficient protocol for the synthesis of S-arylisothiourea derivatives has been achieved in good to excellent yields by reacting a series of aryl iodides with arylthioureas, using inexpensive CuSO₄·5H₂O as catalyst in water without PTC (phase transfer catalyst). The protocol features easy performance, good to excellent yields, good tolerance towards a variety of functional groups, which could be useful for the preparation of some biologically active compounds.     

Palladium-catalyzed homocoupling of aryl halides in the presence of fluoride

This report describes the fluoride-mediated homocoupling of aryl iodides and bromides catalyzed by palladium(0). This coupling protocol is tolerant of electron-donating and electron-withdrawing substitutents on the aryl halide, as well as ortho substitution. Optimum reaction conditions entail 10 mol% Pd(dba)₂, 3 equiv of tetrabutyl ammonium fluoride (TBAF) in DMF at 90 °C.     

Copper-catalyzed cross-coupling of sulfonamides with aryl iodides and bromides facilitated by amino acid ligands

A highly general, convenient, and inexpensive catalyst system was developed for the N-arylation of sulfonamides with aryl iodides or bromides by using 5-20 mol % of CuI as catalyst, 20 mol % of N-methylglycine (for aryl iodides) or N,N-dimethylglycine (for aryl bromides) as ligand, and K₃PO₄ as base.     

Oxidative additions of alkynyl/vinyl iodides to gold and gold-catalyzed vinylation reactions triggered by the MeDalphos ligand

The hemilabile Ad₂P(o-C₆H₄)NMe₂ ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold. The reaction is general. It works with a broad range of substrates of various electronic bias and steric demand, and proceeds with complete retention of stereochemistry from Z and E vinyl iodides. Both alkynyl and vinyl iodides react faster than aryl iodides. The elementary step is amenable to catalysis. Oxidative addition of vinyl iodides to gold and π-activation of alkenols (and N-alkenyl amines) at gold have been combined to achieve hetero-vinylation reactions. A number of functionalized heterocycles, i.e. tetrahydrofuranes, tetrahydropyranes, oxepanes and pyrrolidines were obtained thereby (24 examples, 87% average yield). Taking advantage of the chemoselectivity for vinyl iodides over aryl iodides, sequential transformations involving first a hetero-vinylation step and then a C–N coupling, a C–C coupling or an heteroarylation were achieved from a vinyl/aryl bis-iodide substrate.

The hemilabile Ad₂P(o-C₆H₄)NMe₂ ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold.     

Cu(OAc)2·H2O-catalyzed N-arylation of nitrogen-containing heterocycles

In the absence of any additional ligands, the efficient N-arylation of nitrogen-containing heterocycles with aryl iodides catalyzed by relative low catalyst amount of Cu(OAc)₂·H₂O was developed. This simple catalytic system is involved in the C-N cross-coupling reaction and works for a variety of pyrazole, pyrrole, imidazole, triazole, indole, benzoimidazole, benzotriazole, carbazole, and anilines as well as aryl iodides with different electronic properties. Highly efficient copper(II)-catalyzed N-arylation protocol was established.     

FeCl3/PPh3-catalyzed Sonogashira coupling reaction of aryl iodides with terminal alkynes

Conditions for a FeCl₃/PPh₃-catalyzed and palladium-, copper-, amine free-Sonogashira coupling reaction of aryl halides with terminal alkynes are reported. The protocol was applicable to a wide variety of substituted aryl iodides and alkynes with different steric and electronic properties and gave excellent yields of the desired coupling products.     

Pd(OAc)2-Catalyzed Carbonylative Coupling of Aryl Iodide with Ortho-Haloamines in Water

The carbonylative cross coupling of aryl iodide with ortho-haloaniline to ortho-haloanilide using phosphine-free Pd(OAc)₂ catalyst in water as a reaction medium has been studied. The present protocol facilitated the reaction of o-haloanilines with a wide variety of hindered and functionalized aryl iodides, affording good yields of the desired products. The protocol was also extended for the synthesis of benzoxazoles through cyclization of ortho-haloanilide using Cu(acac)₂ catalyst.     

Efficient copper-catalyzed cross-coupling of 1-Boc-piperazine with aryl iodides and its application in the synthesis of trazodone

A convenient and practical strategy is developed for the cross-coupling of N-Boc protected piperazines with aryl iodides using CuBr/1,1′-bi-2-naphthol as the catalyst and K₃PO₄ as the base. The protocol affords N-arylated piperazine products in moderate to good yields under the optimized conditions. The application of this catalytic system to the synthesis of trazodone is also successfully demonstrated using commercially available substrates.     

Efficient copper-catalyzed coupling of aryl iodides and thiobenzoic acid

A highly efficient copper-catalyzed coupling reaction of aryl iodides and thiobenzoic acid, using 10 mol % of copper iodide, 20 mol % of 1,10-phenanthroline, and ⁱPr₂NEt in toluene, was developed. This methodology is applicable to a variety of aryl iodides.     

Synthesis of N-aryl-d-glucosamines through copper-catalyzed C–N coupling

A catalytic protocol was developed to synthesize N-aryl-d-glucosamines from the corresponding aryl halides. Cross-coupling of 1,3,4,6-tetra-O-benzyl-β-d-glucosamine with aryl iodides or bromides was catalyzed with copper. Subsequent deprotection of the benzyl group gave the arylation product N-aryl-d-glucosamines.     

Synthesis of arylated chalcone derivatives via palladium cross-coupling reactions

A useful protocol for arylation of the olefin double bond of chalcones to afford tri- and tetra-substituted chalcone derivatives is reported. The protocol begins with the Heck reaction between chalcones and aryl iodides providing β-arylchalcones. This reaction tolerates various functional groups on both rings, as well as deactivated aryl iodides. The products are obtained in moderate to excellent yields and the (E)-β-arylchalcones (E:Z?>?96:4) can be isolated via precipitation. Competitive Heck reactions pointed to a significant effect of ring one substituents on the reaction rate, while substituents on ring two have a much smaller effect. To access α,β-diarylchalcones, a sequential bromination-Suzuki cross coupling strategy was applied to the β-arylated compounds which afforded double arylated chalcone derivatives in 60–99% yield over two steps.     

Efficient and highly regioselective direct C-2 arylation of azoles, including free (NH)-imidazole, -benzimidazole and -indole, with aryl halides

The Pd- and Cu-mediated reaction of a large variety of π-electron sufficient heteroarenes, which include free (NH)-imidazoles, -benzimidazole and -indole, with aryl iodides under ligandless and base-free conditions provides regioselectively the required 2-arylheterocycle derivatives in high yields. 2-Aryl-1-phenyl-1H-imidazoles can also be prepared by a one-pot domino HALEX and Pd- and Cu-mediated arylation reactions of 1-phenyl-1H-imidazole with activated and unactivated aryl bromides under base-free and ligandless conditions. The protocol for the synthesis of 2-arylazoles involving the use of aryl iodides has been found to be suitable for the efficient preparation of three bioactive compounds and a key intermediate in the synthesis of a heparanase inhibitor.     

Iron/copper co-catalyzed highly selective arylation of sulfinamides with aryl iodides

In the present study, an inexpensive but efficient Iron(III) and Copper(II) co-catalyst without ligands catalyzed arylation of sulfinamides with aryl iodide was primarily reported. In brief, in the presence of Fe(NO₃)₃·9H₂O, CuO and K₃PO₄, the highly selective C–N cross coupling of several sulfinamides and aryl iodides was achieved in high chemical yield, while the aryl chlorides and bromides could not yield coupling products. It is noteworthy that through the arylation of chiral tert-butanesulfinamide with aryl iodides, N-aryl tert-butanesulfinamides are provided without racemization, even in gram-scale. The possible mechanism was that This oxidative addition process between copper catalyst and aryl-iodides might be significantly accelerated by active Fe(III) species. Moreover, using this synthetic method, a facile and efficient access was developed for the derivatives of N-phenyl sulfinamides, which might help to develop new drug molecules and material chemicals.     

Visible-light-induced cross-coupling of aryl iodides with hydrazones via an EDA-complex

A visible-light-induced, transition-metal and photosensitizer-free cross-coupling of aryl iodides with hydrazones was developed. In this strategy, hydrazones were used as alternatives to organometallic reagents, in the absence of a transition metal or an external photosensitizer, making this cross-coupling mild and green. The protocol was compatible with a variety of functionalities, including methyl, methoxy, trifluoromethyl, halogen, and heteroaromatic rings. Mechanistic investigations showed that the association of the hydrazone anion with aryl halides formed an electron donor–acceptor complex, which when excited with visible light generated an aryl radical via single-electron transfer.

Visible-light-induced catalyst-free cross-coupling of aryl iodides with hydrazones via single-electron-transfer was reported. The mechanistic investigations showed that the association of hydrazone anion with aryl iodides formed an EDA complex.     

Nickel catalysed carbonylative Sonogashira reaction for the synthesis of diarylalkynones and 2-substituted flavones

The nickel catalyzed, palladium/phosphine free carbonylative Sonogashira reaction of terminal alkynes with substituted aryl and heteroaryl iodides is described. This protocol provides mild and robust conditions to synthesize a variety of substituted aryl α,β-alkynyl ketones and flavones in good to excellent isolated yields. This methodology tolerates several functional groups such as electron donating (methyl, isopropyl, tert-butyl, methoxy) as well as electron withdrawing (trifluoromethyl, nitro, esters, nitrile) groups on the terminal alkynes and iodides.     

A modified approach for the site-selective direct C-6 arylation of benzylated uracil

An efficient methodology is reported for the regioselective C-6 arylation of protected uracil via the palladium catalyzed CH functionalization of 1-(4-methoxybenzyl)-3-methylpyrimidine-2,4(1H,3H)-dione with (hetero)aryl halides and boronic acids. Utilization of the Pd(OAc)₂/Xantphos catalytic system with a stoichiometric amount of CuI and DBU as the base was vital for the success of this protocol. The methodology is facile and compatible with aryl bromides, iodides and boronic acids and hence affords broad substrate scope and diversity.     

Copper(I)-catalyzed arylselenylation of aryl bromides and iodides

A new protocol to prepare unsymmetrical diarylselenides using the reaction of aryl bromides and iodides with easily available Bu₃SnSeAr catalyzed by Cu(I) complexes under rather mild conditions and with a very high yield is described.     

Microwave-assisted Pd(OH)2-catalyzed direct C−H arylation of free-(NH2) adenines with aryl halides

A direct C−H arylation of free-(NH₂) adenines using Pd(OH)₂/C (Pearlman’s catalyst) and stoichiometric amount of copper iodide under ligandless microwave activation is described. This new protocol proved to be highly effective to synthesize a variety of 8-aryladenine derivatives 3 without prior protection of the amino substituent. The arylation reaction takes place rapidly within few minutes and allows the coupling to proceed regioselectively at the 8-position with a wide range of aryl halides including aryl iodides, bromides and the less reactive aryl chlorides.