Synthesis of 2,2-diaryl-1,1-difluoroethenes via Pd-catalyzed dehydrosulfonylative cross-coupling of α-[difluoro(phenylsulfonyl)methyl]benzyl tosylates with arylboronic acids

By using PhSO₂CF₂H as the difluoromethylidene equivalent, a novel method for connecting aromatic aldehydes and arylboronic acids via consecutive reactions was developed to obtain structurally diverse 2,2-diaryl-1,1-difluoroethenes. The key step is the palladium-catalyzed dehydrosulfonylative cross-coupling of tosylates that are prepared from PhSO₂CF₂H, aromatic aldehydes and tosyl chloride. Mechanistic investigations showed that the reaction proceeds mainly through base-mediated dehydrosulfonylation followed by palladium-catalyzed C(sp²)-C(sp²) cross-coupling reaction.     

PdCl2-catalyzed cross-coupling reaction of arylacetylene iodides with arylboronic acids to diarylacetylenes

A new Suzuki-type cross-coupling reaction between 1-iodo-2-arylalkynes and arylboronic acids to afford a wide variety of functionalized diarylacetylenes in a mild reaction condition was developed. The reaction was catalyzed by a small amount of a structurally simple, commercially available, and stable PdCl₂. This unique sp-sp² carbon-carbon bond formation provides a new protocol for the synthesis of diarylacetylenes, which is a new addition to the Suzuki cross-coupling reaction.     

A new organic transformation by introducing crotyl/allyltrifluoroborates in cross-coupling reaction with aroyl chlorides

Microwave irradiated PdCl₂(d^tbpf) catalyzed direct cross-coupling reaction of aroyl chlorides with potassium crotyl/allyltrifluoroborates has been developed. Regioselectivity of the cross-coupling product is varied from crotyltrifluoroborate to allyltrifluoroborate.     

Alkaloids of the flora of Siberia and Altai: XX. Synthesis of 5-aryl(hetaryl)-substituted anthranilic acid esters

Cross-coupling of methyl 2-acetylamino-5-bromobenzoate and 5′-bromolappaconitine with aryl-, furyl-, pyridyl-, and 5-acetylthiophen-2-ylboronic acids or 1-(2-fluoroquinolin-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane gave the corresponding 5-aryl(hetaryl)-substituted anthranilic acid derivatives. The use of the two-phase toluene-water system as reaction medium and addition of tetrabutylammonium bromide allows the cross-coupling to be accomplished under mild conditions. The catalytic system Pd(dba)₂-AsPh₃ was found to be efficient in the cross-coupling of methyl 2-acetylamino-5-bromobenzoate with furyl- and pyridylboronic acids, whereas the system Pd(OAc)₂-(o-Tol)₃P ensured good results in the reactions of 5′-bromolappaconitine with hetarylboronic acids. Facile esterification at the C⁸-OH and C⁹-OH groups of the aconitane skeleton was observed in the reactions of 5′-bromolappaconitine and 5′-phenyllappaconitine with phenylboronic acid. 5′-Bromo-8,9-O-(phenylboranediyl)lappaconitine under the Suzuki reaction conditions underwent hydrolysis of the boronic ester moiety with formation of the cross-coupling product of 5′-bromolappaconitine with phenylboronic acid.     

A convenient hydroiodination of alkynes using I2/PPh3/H2O and its application to the one-pot synthesis of trisubstituted alkenes via iodoalkenes using Pd-catalyzed cross-coupling reactions

A facile hydroiodination of alkynes using readily-available reagents such as I₂, PPh₃, and H₂O has been developed. This is extended to the one-pot synthesis of trisubstituted alkenes from alkynes via iodoalkenes using Pd-catalyzed cross-coupling and related methods such as the Suzuki–Miyaura cross-coupling, Sonogashira cross-coupling reaction, and Mizoroki–Heck reaction.     

Palladium-catalyzed direct cross-coupling of potassium styryltrifluoroborates and benzoyl chlorides—a one step method for chalcone synthesis

A direct cross-coupling reaction of benzoyl chlorides and potassium styryltrifluoroborates to the corresponding α,β-unsaturated aromatic ketones in the presence of PdCl₂(d^tbpf) catalyst under microwave heating is developed.     

Preparation of 1,3-dienyl organotrifluoroborates and their Diels-Alder/cross-coupling reactions

2-BF₃-substituted 1,3-butadienes with potassium and tetrabutyl ammonium counterions have been prepared in gram quantities from chloroprene via a simple synthetic procedure. The potassium salt of this new main group element substituted diene has been characterized by ¹H, ¹³C, ¹¹B, and ¹⁹F NMR and the tetra n-butyl ammonium salt was also characterized by X-ray crystallography. Diels-Alder reactions of these dienes with dienophiles such as ethyl acrylate, methyl vinyl ketone, and N-phenylmaleimide are reported as well as subsequent Pd-catalyzed cross-coupling reactions of those Diels-Alder adducts. 4-Phenyl-2-BF₃-substituted 1,3-diene was prepared by magnesium-halogen exchange from the corresponding 2-bromo and iodo dienes. The 4-phenyl-2-bromo-1,3-butadiene was also characterized by X-ray crystallography. 4-Phenyl-2-BF₃-1,3-butadiene was used in Diels-Alder/cross-coupling reactions and the product of a Diels-Alder reaction with N-phenylmaleimide followed by cross-coupling with 4-bromo-benzonitrile was also characterized by X-ray crystallography.     

Palladium-catalyzed reaction of some triphenylbismuth(V) sulfonates and phenolates with methyl acrylate

Triphenylbismuth(V) derivatives Ph₃BiX₂ [X = OC₆H₂(NO₂)₃-2,4,6, OC₆H₂(NO₂-4)Br₂-2,6, OTs, OSO₂C₆H₄OH-4] react with methyl acrylate and PdCl₂ (1:3:0.04 molar ratio) in acetonitrile at 20°C to form the cross-coupling products, methyl cinnamate (0.26–0.51 mol mol^?1 starting bismuth compound) and methyl hydrocinnamate (0–0.17 mol mol^?1); diphenyl, the homocoupling product (0–0.13 mol mol^?1); and benzene (0.02–0.15 mol mol^?1). The reaction of Ph₃Bi(OSO₂C₆H₄OH-4)₂ is characterized by the selective formation of methyl cinnamate, but the reagent activity is low. Ph₃Bi(OTs)₂ exhibits the highest activity among the derivatives studied, but the reaction selectivity is low. The mechanisms of the palladium-catalyzed formation of homo-and cross-coupling products are proposed.     

Carbon–Phosphorus Coupling from C^N Cyclometalated AuIII Complexes

With the aim of exploiting new organometallic species for cross-coupling reactions, we report here on the Au^III-mediated C_aryl−P bond formation occurring upon reaction of C^N cyclometalated Au^III complexes with phosphines. The [Au(C^N)Cl₂] complex 1 featuring the bidentate 2-benzoylpyridine (C^CON) scaffold was found to react with PTA (1,3,5-triaza-7-phosphaadamantane) under mild conditions, including in water, to afford the corresponding phosphonium 5 through C−P reductive elimination. A mechanism is proposed for the title reaction based on in situ ³¹P{¹H} NMR and HR-ESI-MS analyses combined with DFT calculations. The C−P coupling has been generalized to other C^N cyclometalated Au^III complexes and other tertiary phosphines. Overall, this work provides new insights into the reactivity of cyclometalated Au^III compounds and establishes initial structure–activity relationships to develop Au^III-mediated C−P cross-coupling reactions.     

Well-Defined Ni(0) and Ni(II) Complexes of Bicyclic (Alkyl)(Amino)Carbene (MeBICAAC): Catalytic Activity and Mechanistic Insights in Negishi Cross-Coupling Reaction

Negishi cross-coupling reaction of organozinc compounds as nucleophiles with aryl halides has drawn immense focus for C−C bond formation reactions. In comparison to the well-established library of Pd complexes, the C−C cross-coupling of this particular approach is largely primitive with nickel-complexes. Herein, we describe the syntheses of Ni(II) complexes, [(^MeBICAAC)₂NiX₂] (X=Cl ( 1 ), Br ( 2 ), and I ( 3 )) by employing the bicyclic (alkyl)(amino)carbene (^MeBICAAC) ligand. The reduction of complexes 1 – 3 using KC₈ afforded the two coordinate low valent, Ni(0) complex, [(^MeBICAAC)₂Ni(0)] ( 4 ). Complexes 1 – 4 have been characterized by spectroscopic techniques and their solid-state structures were also confirmed by X-ray crystallography. Furthermore, complexes 1 – 4 have been applied in a direct and convenient method to catalyze the Negishi cross-coupling reaction of various aryl halides with 2,6-difluorophenylzinc bromide or phenylzinc bromide as the coupling partner in the presence of 3 mol % catalyst. Comparatively, among all-pristine complexes, 1 exhibit high catalytic potential to afford value-added C−C coupled products without the use of any additive. The UV-vis studies and HRMS measurements of controlled stochiometric reactions vindicate the involvement of Ni(I)−NI(III) cycle featured with a penta-coordinated Ni(III)-aryl species as the key intermediate for 1 whereas Ni(0)/Ni(II) species are potentially involved in the catalytic cycle of 4 .     

Remarkable regioselectivity in microwave-enhanced palladium-catalyzed allylation reaction involving allyltrifluoroborates and aryl halides

An unprecedented cross-coupling reaction of potassium allyltrifluoroborates and aryl halides to the corresponding trans-β-methylstyrenes in the presence of PdCl₂(d^tbpf) catalyst under microwave heating was developed.     

Visible-Light-Initiated Palladium-Catalyzed Cross-coupling by PPh3 Uncaging from an Azobenzene Ruthenium–Arene Complex

Photo-release of triphenylphosphine from a sulfonamide azobenzene ruthenium–arene complex was exploited to activate Pd^IICl₂ into Pd⁰ catalyst, for the photo-initiation of Sonogashira cross-coupling. The transformation was initiated on demand – by using simple white LED strip lights – with a high temporal response and the ability to control reaction rate by changing the irradiation time. Various substrates were successfully applied to this photo-initiated cross-coupling, thus illustrating the wide functional-group tolerance of our photo-caged catalyst activator, without any need for sophisticated photochemistry apparatus.     

New acyclic aminocarbene palladium(ii) complexes as convenient catalysts for the Sonogashira and Suzuki cross-coupling

A reaction of isocyanide complex cis-[PdCl₂(CNAr)₂] with hydrazones H₂N-N=CR¹R² proceeded at the carbon atom of one of the isocyanide groups and gave the corresponding diaminocarbene isocyanide palladium(ii) complexes. These complexes showed high catalytic activity in the Sonogashira and Suzuki cross-coupling reactions.     

Unusual ligand-dependent chemoselective Suzuki-Miyaura cross-coupling reactions of 3-bromo-4-trifloyl-thiophenes

An unusual ligand-dependent chemoselective Suzuki-Miyaura cross-coupling reaction for 3-bromo-4-trifloyl-thiophenes was discovered. Pd(PPh₃)₄ showed selectivity for triflate over bromide, whereas the selectivity was reversed for Pd(^tBu₃P)₂.     

Stereoselective C(sp3)-C(sp2) Negishi coupling of (2-amido-1-phenylpropyl)zinc compounds through the steric control of β-amido group

A controllable diastereoselective C(sp2)-C(sp3) Negishi coupling reaction of secondary benzylic zinc reagents with aryl bromides has been demonstrated for the first time, forming medicinally important 1-arylphenylethylamines. In the presence of Pd(OAc) 2 and S-phos, open-chain (2-amido-1-phenylethyl)zinc reagents bearing a -NHAc or NHCHO group underwent cross-coupling reaction to give syn 1-arylphenylethylamine as the major products, whereas the zinc reagents bearing a sterically hindered-NHCOC(CH3)2 OTBS group specifically yielded anti 1-arylphenylethylamines.     

Computational study of the transmetalation process in the Suzuki-Miyaura cross-coupling of aryls

The transmetalation step of the Suzuki-Miyaura cross-coupling between aryl groups is analyzed by means of DFT calculations with the Becke3LYP functional. The halide considered is Ph-Br, and the organoboronic acid is Ph-B(OH)₂. The model catalyst is Pd(PH₃)₂, and the base, OH⁻. The transmetalation is considered to start from the Pd(Ph)(PH₃)₂Br complex, the product of the oxidative addition. The results are compared with those of a previous study on the analogous reaction with vinyl groups, and it is shown that the reaction mechanism is very similar.     

Origin of the different reactivity of the high-valent coinage-metal complexes [RCuiiiMe3]− and [RAgiiiMe3]− (R=allyl)**

High-valent tetraalkylcuprates(iii ) and -argentates(iii ) are key intermediates of copper- and silver-mediated C−C coupling reactions. Here, we investigate the previously reported contrasting reactivity of [RMⁱⁱⁱ Me₃]⁻ complexes (M=Cu, Ag and R=allyl) with energy-dependent collision-induced dissociation experiments, advanced quantum-chemical calculations and kinetic computations. The gas-phase fragmentation experiments confirmed the preferred formation of the [RCuMe]⁻ anion upon collisional activation of the cuprate(iii ) species, consistent with a homo-coupling reaction, whereas the silver analogue primarily yielded [AgMe₂]⁻, consistent with a cross-coupling reaction. For both complexes, density functional theory calculations identified one mechanism for homo coupling and four different ones for cross coupling. Of these pathways, an unprecedented concerted outer-sphere cross coupling is of particular interest, because it can explain the formation of [AgMe₂]⁻ from the argentate(iii ) species. Remarkably, the different C−C coupling propensities of the two [RMⁱⁱⁱ Me₃]⁻ complexes become only apparent when properly accounting for the multi-configurational character of the wave function for the key transition state of [RAgMe₃]⁻. Backed by the obtained detailed mechanistic insight for the gas-phase reactions, we propose that the previously observed cross-coupling reaction of the silver complex in solution proceeds via the outer-sphere mechanism.     

A highly efficient memantine-modified palladium catalyst for Suzuki–Miyaura cross-coupling reaction

A new simple Pd(memantine)₂Cl₂ complex was synthesized and characterized by ¹H NMR, ¹³C NMR and X-ray single crystal structure determination. The Suzuki–Miyaura reaction of aryl bromides catalyzed by Pd(memantine)₂Cl₂ complex was investigated in air with different temperature. The high turnover numbers of 650,000 have been obtained in the reaction of 4-bromonitrobenzene with phenylboronic acid at 80 °C. At room temperature, the complex also showed high activity for Suzuki–Miyaura cross-coupling reaction of aryl bromides with a wide range of functional groups under air, and the turnover number of up to 99,000 was achieved. The catalytic system also gives good yields toward the reaction of several heteroaryl bromides with thiophenylboronic acid.     

Pd-NHC catalyzed Suzuki cross-coupling of benzyl ammonium salts

A palladium-catalyzed Suzuki cross-coupling of benzyl ammonium triflates via activation of a Csp³–N bond to construct a Csp³–Csp² bond is described. Various boronic acids can be coupled with a range of benzylamine-derived quaternary ammonium salts in 1:1 molar ratio by the bench-stable N-heterocyclic carbene palladium complex, SIPr-PdCl₂-Py to afford diarylmethane derivatives. This reaction exhibits a wide substrate scope and functional group tolerance. Direct arylation of benzylamine in a one-pot process and the gram-scale reaction can be performed successfully.

     

Practical synthesis of biaryl colchicinoids containing 3,4-catechol ether-based A-rings via Suzuki cross-coupling with ligandless palladium in water

Eight new biaryl colchicinoids containing 3^′,4^′-methylene or benzodioxy ether bridges were synthesized. The key synthetic step employed a ligandless, aqueous Suzuki cross-coupling reaction catalyzed by Pd(OAc)₂ with tetrabutylammonium bromide (TBAB) and potassium carbonate (K₂CO₃). The biaryl Suzuki products were typically formed in 5-30 min and always in less than 1 h.