Palladium-catalyzed borylation of aryl halides or triflates with dialkoxyborane: A novel and facile synthetic route to arylboronates

A direct borylation of aryl halides or triflates with dialkoxyborane was investigated. The coupling reaction of pinacolborane with aryl halides or triflates in the presence of a catalytic amount of PdCl(2)(dppf) together with a base provided arylboronates in high yields. The product distributions were strongly dependent on the base employed, and the tertiary amine, especially Et(3)N, was effective for the selective formation of the boron-carbon bond. The reaction conditions were so mild that arylboronates having a variety of functional groups such as carbonyl, cyano, and nitro groups were readily prepared.     

Revisiting the Hirao cross-coupling: improved synthesis of aryl and heteroaryl phosphonates

The palladium-catalyzed cross-coupling of dialkylphosphite with aromatic electrophiles (Hirao coupling) was re-investigated. Some limitations in terms of palladium loadings and substrate reactivity are alleviated with the use of Pd(OAc)₂ complexed to 1,1′-bis(diphenylphosphino)ferrocene (dppf) as a ligand. Various aryl and heteroaryl halides are employed to deliver both known and novel substituted phosphonates. The first examples of aryl chloride couplings are also reported.     

Scope of direct arylation of fluorinated aromatics with aryl sulfonates

The scope and limitations of direct arylation of fluorinated aromatics with aryl sulfonates was examined. Pd(OAc)(2), in the presence of MePhos and KOAc in THF, efficiently catalyzed the direct arylation of fluoro aromatics with aryl triflates under ambient conditions. Sterically hindered triflates and heteroaryl triflates gave good to excellent yields of the cross coupled products using a modified catalyst system which involves Pd(OAc)(2)-RuPhos at 100 °C. The direct arylation of electron deficient arenes with aryl mesylates is also established using Pd(OAc)(2)-SPhos as the catalyst in toluene-(t)BuOH at 120 °C.     

A versatile palladium catalyst system for Suzuki-Miyaura coupling of alkenyl tosylates and mesylates

A general and effective palladium system for Suzuki-Miyaura coupling of alkenyl electrophiles under mild reaction conditions is reported. With the Pd(OAc)(2)/CM-phos system, a variety of alkenyl tosylates are coupled well with ArB(OH)(2). Moreover, the first successful examples of using alkenyl mesylates in alkenylation are also described.     

Expeditious synthesis of 1,1-diarylethylenes related to isocombretastatin A-4 (isoCA-4) via palladium-catalyzed arylation of N-tosylhydrazones with aryl triflates

A quick and efficient entry to 1,1-diarylethylenes via the reaction of polyoxygenated aryl N-tosylhydrazones with aryl triflates is described. The reaction employs the catalytic system Pd(OAc)₂/XPhos, tBuOLi as the base and dioxane as the solvent. A variety of substituents on both the coupling partners’ hydrazones and triflates are tolerated. This procedure provides a complementary route to the existing methods for the access to 1,1-diarylethylenes of biological interest.     

Dabco as an inexpensive and highly efficient ligand for palladium-catalyzed Suzuki-Miyaura cross-coupling reaction

An inexpensive and highly efficient Pd(OAc)(2)/Dabco catalytic system has been developed for the cross-coupling of aryl halides with arylboronic acids. A combination of Pd(OAc)(2) and Dabco (triethylenediamine) was observed to form an excellent catalyst, which affords high TONs (turnover numbers; TONs up to 950 000 for the reaction of PhI and p-chlorophenylboronic acid) for Suzuki-Miyaura cross-coupling of various aryl iodides and bromides with arylboronic acids. [reaction: see text]     

A nickel precatalyst for efficient cross-coupling reactions of aryl tosylates with arylboronic acids: vital role of dppf

An air-stable and easy-to-handle nickel precatalyst, (9-phenanthrenyl)Ni(II)(PPh₃)₂Cl, was examined for the cross-coupling reactions of aryl tosylates with arylboronic acids. Under the optimized reaction conditions, the catalytic system tolerates a wide range of activated, neutral and deactivated substrates. The selectivity of this cross-coupling reaction towards aryl tosylates and arylboronic acids has been investigated. It is proposed that ligand 1,1′-bis(diphenylphosphino)ferrocene (dppf) plays a key role in the coupling by enforcing a cis geometry in key intermediates and the active Ni(0) species.     

Palladium-catalyzed coupling of pyrazole triflates with arylboronic acids

[reaction: see text] A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.     

Palladium-catalyzed tetrakis(dimethylamino)ethylene-promoted reductive coupling of aryl halides

Tetrakis(dimethylamino)ethylene (TDAE)/cat. PdCl(2)(PhCN)(2)-promoted reductive coupling of aryl bromides having either electron-donating or electron-withdrawing groups on their para- and/or meta-position proceeded smoothly to afford the corresponding biaryls in good to excellent yields. Notably, TDAE is such a mild reductant that easily reducible groups, such as carbonyl and nitro groups, are tolerate. A similar reductive coupling of ortho-substituted aryl bromides did not occur at all. The proper choice of palladium catalysts is essential for the reductive coupling; thus, PdCl(2)(PhCN)(2), PdCl(2)(MeCN)(2), Pd(hfacac)(2), Pd(2)(dba)(3), PdCl(2), and Pd(OAc)(2) were used successively for this reaction, but phosphine-ligated palladium catalysts such as Pd(PPh(3))(4), PdCl(2)(PPh(3))(2), and Pd(dppp) did not promote the reaction. The reductive coupling did not occur with nickel catalysts such as NiBr(2), NiCl(2)(bpy), and Ni(acac)(2). The TDAE/cat. palladium-promoted reductive coupling of aryl halides having electron-withdrawing groups took place more efficiently than that of aryl halides substituted with electron-donating groups. A plausible mechanism of TDAE/cat. palladium-promoted reaction is discussed.     

Nickel-catalyzed C-H/C-O coupling of azoles with phenol derivatives

The first nickel-catalyzed C-H bond arylation of azoles with phenol derivatives is described. The new Ni(cod)(2)/dcype catalytic system is active for the coupling of various phenol derivatives such as esters, carbamates, carbonates, sulfamates, triflates, tosylates, and mesylates. With this C-H/C-O biaryl coupling, we synthesized a series of privileged 2-arylazoles, including biologically active alkaloids. Moreover, we demonstrated the utility of the present reaction for functionalizing estrone and quinine.     

Enantioselective alpha-arylation of ketones with aryl triflates catalyzed by difluorphos complexes of palladium and nickel

The asymmetric alpha-arylation of ketones with aryl triflates is described, and the use of this electrophile with nickel and palladium catalysts containing a segphos derivative increases substantially the scope of highly enantioselective arylations of ketone enolates. The combination of aryl triflates as reactant, difluorphos as ligand, palladium catalysts for reactions of electron-neutral or electron-rich aryl triflates, and nickel catalysts for reactions of electron-poor aryl triflates led to a series of alpha-arylations of tetralone, indanone, cyclopentanone, and cyclohexanone derivatives. Enantioselectivities ranged from 70% to 98% with 10 examples over 90%. Systematic studies on these alpha-arylations have revealed a number of factors that affect enantioselectivity. Ligands containing biaryl backbones with smaller dihedral angles generate catalysts that react with higher enantioselectivity than related ligands with larger dihedral angles. In addition, faster rates for reactions of aryl triflates versus those for reactions of aryl bromides allow the alpha-arylations of aryl triflates to be conducted at lower temperatures, and this lower temperature improves enantioselectivity. Finally, studies that compare the enantioselectivities of catalytic reactions to those of stoichiometric reactions of isolated [(segphos)Pd(Ar)(Br)], [(segphos)Pd(Ar)(I)], and [(segphos)Ni(C6H4-4-CN)Br] suggest that catalyst decomposition affects enantioselectivity.     

The first general palladium catalyst for the Suzuki-Miyaura and carbonyl enolate coupling of aryl arenesulfonates

The first general method for the palladium-catalyzed Suzuki-Miyaura and carbonyl enolate coupling of unactivated aryl arenesulfonates was developed utilizing XPhos, 1, and Pd(OAc)2. This is of significant interest because aryl tosylates and aryl benzenesulfonates are more easily handled and considerably less expensive than aryl triflates. This catalyst system effects the coupling of a variety of aryl, heteroaryl, and extremely hindered arylboronic acids with different aryl tosylates, under mild conditions. The same catalyst was employed in the first carbonyl enolate coupling of aryl arensulfonates.     

Palladium-catalyzed cross-coupling of B-benzyl-9-borabicyclo[3.3.1]nonane to furnish methylene-linked biaryls

[reaction: see text] Benzylboranes are noticeably uncommon partners within Suzuki-Miyaura coupling reactions. B-Benzyl-9-BBN was successfully coupled to a range of aryl/heteroaryl bromides, chlorides, and triflates to give pharmacologically important methylene-linked biaryl structures. Activated, deactivated, and sterically hindered substrates were successfully coupled in high yield using Pd(PPh(3))(4) or Pd(OAc)(2) with SPhos as the catalyst system.     

Catalytic Hydroalkylation of Allenes

We have developed a catalytic method for the hydroalkylation of allenes using alkyl triflates as electrophiles and silane as a hydride source. The reaction has an excellent substrate scope and is compatible with a wide range of functional groups, including esters, aryl halides, aryl boronic esters, sulfonamides, alkyl tosylates, and alkyl bromides. We found evidence for a reaction mechanism that involves unusual dinuclear copper ally complexes as catalytic intermediates. The unusual structure of these complexes provides a rationale for their unexpected reactivity.     

B-alkyl suzuki-miyaura cross-coupling reactions with air-stable potassium alkyltrifluoroborates

The palladium-catalyzed cross-coupling reaction of substituted potassium alkyltrifluoroborates with aryl halides and aryl triflates proceeds readily with moderate to good yields. The potassium alkyltrifluoroborates 1, 2, and 3a-e were easily synthesized and obtained as air-stable crystalline solids that can be stored for long periods of time. All of the cross-couplings proceed under the same reaction conditions using PdCl(2)(dppf).CH(2)Cl(2) as catalyst in THF-H(2)O in the presence of 3 equiv of Cs(2)CO(3) as base.     

Ni(COD)2/PCy3 catalyzed cross-coupling of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates in THF at room temperature

Reaction conditions for the Ni(COD)(2)/PCy(3) catalyzed cross-coupling of aryl neopentylglycolboronates with aryl mesylates were developed. By using optimized reaction conditions, Ni(COD)(2)/PCy(3) was shown to be a versatile catalyst for the cross-coupling of a diversity of aryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates containing both electron-donating and electron-withdrawing substituents in their para, ortho, and meta positions in THF at room temperature. This Ni-catalyzed cross-coupling of aryl neopentylglycolboronates is also effective for the synthesis of heterobiaryls and biaryls containing electrophilic functionalities sensitive to organolithium and organomagnesium derivatives. In combination with the recently developed Ni-catalyzed neopentylglycolborylation, all Ni-catalyzed routes to functional biaryls and heterobiaryls are now easily accessible.     

Simple amine/Pd(OAc)(2)-catalyzed suzuki coupling reactions of aryl bromides under mild aerobic conditions

A new palladium catalyst (DAPCy) made from Pd(OAc)(2) and commercially available, inexpensive dicyclohexylamine has been developed for the Suzuki coupling reaction of aryl bromides with boronic acids to give the coupling products in good to high yields. The air-stable catalyst was characterized and well-defined by X-ray crystallography. A catalytic system involving DAPCy in dioxane demonstrates a temperature-dependent reactivity toward aryl bromides with different electronic substituents, and selectively couples electron-deficient aryl bromides with boronic acids over electron-rich ones at room temperature. Another catalytic system employing DAPCy in EtOH provides a general and convenient method to prepare biaryls from aryl bromides and boronic acids with a broad range of functional groups at room temperature and under aerobic conditions.     

Amination reactions of aryl halides with nitrogen-containing reagents mediated by palladium/imidazolium salt systems.

Nucleophilic N-heterocyclic carbenes have been conveniently used as catalyst modifiers in amination reactions involving aryl chlorides, aryl bromides, and aryl iodides with various nitrogen-containing substrates. The scope of a coupling process using a Pd(0) or Pd(II) source and an imidazolium salt in the presence of a base, KO(t)Bu or NaOH, was tested using various substrates. The Pd(2)(dba)(3)/IPr.HCl (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) system presents the highest activity with respect to electron-neutral and electron-rich aryl chlorides. The ligand is also effective for the synthesis of benzophenone imines, which can be easily converted to the corresponding primary amines by acid hydrolysis. Less reactive indoles were converted to N-aryl-substituted indoles using as supporting ligand the more donating SIPr.HCl (5, SIPr = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene). The Pd(OAc)(2)/SIPr.HCl/NaOH system is efficient for the N-arylation of diverse indoles with aryl bromides. The general protocol developed has been applied successfully to the synthesis of a key intermediate in the synthesis of an important new antibiotic. Mechanistically, palladium-to-ligand ratio studies strongly support an active species bearing one nucleophilic carbene ligand.     

Direct synthesis of 4-arylpiperidines via palladium/copper(I)-cocatalyzed Negishi coupling of a 4-piperidylzinc iodide with aromatic halides and triflates

A general procedure for the synthesis of 4-arylpiperidines via the coupling of 4-(N-BOC-piperidyl)zinc iodide with aryl halides and triflates is presented. The reaction requires cocatalysis with both Cl(2)Pd(dppf) and a copper(I) species. An improved, safer procedure for the activation of zinc dust is also presented.     

Mild and efficient nickel-catalyzed Heck reactions with electron-rich olefins

A new efficient protocol for the nickel-catalyzed Heck reaction of aryl triflates with vinyl ethers is presented. Mild reaction conditions that equal those of the corresponding palladium-catalyzed Heck reaction are applied, representing a practical and more sustainable alternative to the conventional regioselective arylation of vinyl ethers. A catalytic system comprised of Ni(COD)(2) and 1,1'-bis(diphenylphosphino)ferrocene (DPPF) in combination with the tertiary amine Cy(2)NMe proved effective in the olefination of a wide range of aryl triflates. Both electron-deficient and electron-rich arenes proved compatible, and the corresponding aryl methyl ketone could be secured after hydrolysis in yields approaching quantitative. Good functional group tolerance was observed matching the characteristics of the analogous Pd-catalyzed Heck reaction. The high levels of catalytic activity were explained by the intermediacy of a cationic nickel(II) complex potentially responsible for the successive β-hydride elimination and base promoted catalyst regeneration. Although these elementary reactions are normally considered challenging, DFT calculations suggested this pathway to be favorable under the applied reaction conditions.