Palladium‐Catalyzed α‐Arylation of Methyl Sulfonamides with Aryl Chlorides

A palladium‐catalyzed α‐arylation of sulfonamides with aryl chlorides is presented. A Buchwald‐type pre‐catalyst formed with Kwong’s indole‐based ligand enabled this transformation to be compatible with a large variety of methyl sulfonamides and aryl chlorides in good to excellent yields. Importantly, under the optimized reaction conditions, only mono‐arylated products were observed. This method has been applied to the efficient synthesis of sumatriptan, which is used to treat migraines.

     

An Improved Protocol for Palladium‐Catalyzed Alkoxycarbonylations of Aryl Chlorides with Alkyl Formates

The palladium‐catalyzed alkoxycarbonylation of aryl and heteroaryl halides using butyl formate has been investigated. In the presence of palladium(II) acetate/n‐butylbis(1‐adamantyl)phosphine ( L1 ), and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) as base for the first time non‐activated chloroarenes can be conveniently carbonylated in good yields.     

Palladium‐Catalyzed Efficient and One‐Pot Synthesis of Diarylacetylenes from the Reaction of Aryl Chlorides with 2‐Methyl‐3‐butyn‐2‐ol

An efficient and practical synthetic method has been developed for the preparation of symmetrical diarylacetylenes from the direct reaction of aryl chlorides with 2‐methyl‐3‐butyn‐2‐ol catalyzed by palladium(II) chloride‐bis(tricyclohexylphosphine) [PdCl₂(PCy₃)₂] under mild reaction conditions. Unsymmetrical diarylated acetylenes could be also obtained by using two different aryl chlorides simultaneously. The catalytic procedure includes a novel one‐pot palladium‐catalyzed, double Sonogashira coupling of inactivated aryl chlorides without use of copper(I) as co‐catalyst.     

Progress in the Palladium‐Catalyzed α‐Arylation of Ketones with Chloroarenes

Non‐ and deactivated chloroarenes can be coupled with a wide range of ketones to yield the corresponding arylmethyl ketones in good to excellent yields using a palladium(II) acetate/n‐BuPAd₂ catalyst system. Depending on the ketone, the chloroarene/ketone ratio and the base, mono or diarylation can be effected selectively.     

Palladium‐Catalyzed,Highly Efficient,Regiocontrolled Arylation of Electron‐Rich Allylamines with Aryl Halides

The highly efficient and regioselective palladium‐catalyzed Heck coupling of aryl bromides with electron‐rich allylamine derivatives is described. It was found that the choice of solvent, olefin, ligand and additive had a fundamental influence on the regioselectivity and reactivity of the reaction. The combination of palladium acetate [Pd(OAc)₂] and 1,3‐bis(diphenylphosphino)propane (dppp) in ethylene glycol (EG) constitutes a highly effective catalyst system for internal arylation of N‐Boc‐allylamine (tert‐butyl methyl allyliminodicarbonate) with aryl bromides to give good to excellent regioselectivities, while the catalyst system consisting of Pd(OAc)₂, tetrabutylammonium bromide (TBAB) and 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) additive allows for a variety of aryl bromides to react efficiently with N,N‐(Boc)₂‐allylamine (di‐tert‐butyl allyliminodicarbonate) in water to exclusively afford the linear (E)‐allylamine products in high yields.     

A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides

An efficient system for the direct catalytic intermolecular α‐arylation of acetamide derivatives with aryl bromides and chlorides is presented. The palladium catalyst is supported by Kwong’s indole‐based phosphine ligand and provides monoarylated amides in up to 95% yield. Excellent chemoselectivities (>10:1) in the mono‐ and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and stoichiometry. Under the coupling conditions, the weakly acidic α‐protons of amides (pK_a up to 35) were reversibly depotonated by lithium tert‐butoxide (LiO‐t‐Bu), sodium tert‐butoxide (NaO‐t‐Bu) or sodium bis(trimethylsilyl)amide [NaN(SiMe₃)₂].

     

Palladium‐Catalyzed Methoxylation of Aromatic Chlorides with Borate Salts

Herein we disclose a simple palladium‐catalyzed transformation for the methoxylation of aromatic chlorides with tetramethoxyborate salts. The procedure provides a new and efficient synthetic tool for the introduction of a methoxy group into aromatic systems. In addition, the reaction can be achieved using a wide range of aromatic and heteroaromatic chlorides, the cheapest class of halides.

     

Phosphorus‐Carbon Bond Formation: Palladium‐Catalyzed Cross‐Coupling of H‐Phosphinates and Other P(O)H‐Containing Compounds

Two generally applicable systems have been developed for the cross‐coupling of P(O)H compounds with C_sp2 X and related partners. Palladium catalysis using a ligand/additive combination, typically either xantphos/ethylene glycol or 1,1′‐bis(diphenylphosphino)ferrocene/1,2‐dimethoxyethane, with diisopropylethylamine as the base, proved to be generally useful for the synthesis of numerous P C containing compounds. Routinely, 2 mol% of catalyst are employed (less than half the amount typically employed in most other literature reports). In most cases, excellent results are obtained with a variety of electrophiles (RX, where R=alkenyl, allyl, alkynyl, etc.). The full account of our studies is disclosed, including tandem hydrophosphinylation/coupling and coupling/coupling for doubly catalytic phosphorus‐carbon bond formation. The methodology compares favorably with any existing literature report. The use of an additive appears to be a generally useful strategy to control the reactivity of phosphinylidene compounds.     

Palladium‐Catalysed Direct Desulfitative Arylation of Pyrroles using Benzenesulfonyl Chlorides as Alternative Coupling Partners

The reactivity of pyrrole derivatives for palladium‐catalysed desulfitative arylation has been investigated. 1‐Methyl‐, 1‐phenyl‐ and 1‐benzylpyrroles were successfully coupled with a variety of benzenesulfonyl chlorides using a phosphine‐free catalyst. Highly regioselective arylations at carbon C2 of pyrroles were observed in all cases. A wide variety of substituents on the benzenesulfonyl derivative was tolerated. It should be noted that even bromo‐ and iodo‐benzenesulfonyl chlorides were successfully coupled with pyrrole derivatives without cleavage of the C Br or C I bonds, allowing further transformations. Surprisingly, with indoles, mixtures of C2‐ and C3‐arylation products were obtained.

     

Highly Active Palladium Catalyst for the Sonogashira Coupling Reaction of Unreactive Aryl Chlorides

This communication reports on the β‐diketiminatophosphane palladium‐catalyzed copper‐free Sonogashira coupling of aryl chlorides with alkynes. A catalyst loading of 0.5 mol% is sufficient to achieve high performance under relatively mild reaction conditions. Furthermore, dialkynylbenzenes are efficiently prepared by one‐pot double Sonogashira couplings of aryl dichlorides.     

Phosphine‐Free Palladium‐Catalyzed Decarboxylative Coupling of Alkynylcarboxylic Acids with Aryl and Heteroaryl Halides

We herein report the design and development of a carboxyamido/carbene ligand and its Pd‐complex for the decarboxylative coupling of alkynylcarboxylic acids with aryl and heteroaryl halides to afford arylalkynes.     

First Application of Secondary Phosphines as Supporting Ligands for the Palladium‐Catalyzed Heck Reaction: Efficient Activation of Aryl Chlorides

Secondary dialkylphosphines were successfully used for the first time as efficient supporting ligands for the palladium‐catalyzed Heck reaction of electron‐rich and electron‐poor aryl chlorides with olefins such as acrylate, ethylene, styrene, and n‐butyl vinyl ether. The yields with HP(t‐butyl)₂ and HP(adamantyl)₂ were comparable or better than those obtained with known systems of tertiary phosphines such as P(cyclohexyl)₃ and P(t‐butyl)₃, especially at a catalyst loading of <1 mol %. In comparison with tertiary phosphines, the secondary phosphines have the advantage of being readily available at low cost on a technical scale, and are comparable with respect to handling and oxygen sensitivity.     

Palladium‐Catalyzed Regioselective and Stereoselective Oxidative Heck Arylation of Allylamines with Arylboronic Acids

A general and convenient palladium‐catalyzed oxidative Heck arylation of both N‐protected and N,N‐diprotected allylic amines with arylboronic acids under mild conditions has been developed. The catalyst system, consisting of Pd(OAc)₂ (palladium acetate), AgOAc (silver acetate) and KHF₂ (potassium hydrogen fluoride), could efficiently catalyze the coupling reaction in acetone without the aid of any ligand, leading exclusively to the γ‐arylated allylic amine products in good to excellent yields. This method is highlighted with excellent regio‐ and stereocontrol and remarkable functional group tolerance. The carbamate moiety in allylic amine substrates is of crucial importance to the catalytic performance, and the chelation between the carbonyl O (oxygen) and Pd (palladium) atoms is believed to be responsible for the high regioselectivity and stereoselectivity observed.     

Palladium‐Catalyzed Direct Denitrogenative C‐3‐Arylation of 1H‐Indoles with Arylhydrazines using Air as the Oxidant

A novel palladium‐catalyzed approach to direct C‐3‐arylation of 1H‐indoles with arylhydrazines using air as the oxidant via C N bond cleavage has been developed. Various substituents are tolerated in this system in moderate to good yields. This reaction could also be compatible with a larger scale. Thus, this strategy using arylhydrazines as arylating reagents provides a powerful method for constructing substituted 3‐aryl‐1H‐indoles.     

Palladium‐Catalyzed N‐Arylations of 1,4,7‐Triazacyclononanes

Various 1,4,7‐triazacyclononanes have been N‐arylated by palladium catalysis. Using optimized Buchwald–Hartwig protocols the corresponding products have been obtained in high yields.     

Palladium‐Catalyzed Direct Arylations of 1,2,3‐Triazoles with Aryl Chlorides using Conventional Heating

Generally applicable, palladium‐catalyzed direct arylations of 1,2,3‐triazoles with aryl chlorides were accomplished through conventional heating at reaction temperatures of 105–120 °C. Thereby, intra‐ and intermolecular C H bond functionalizations were achieved with a variety of differently substituted chlorides as electrophiles, bearing numerous valuable functional groups.     

Direct C‐2 Alkylation of Quinoline N‐Oxides with Ethers via Palladium‐Catalyzed Dehydrogenative Cross‐Coupling Reaction

An efficient and concise one‐pot strategy for the direct alkylation of quinoline N‐oxides via palladium‐catalyzed dual C H bonds activation has been developed. This methodology provides quinoline‐containing heterocyclic molecules in moderate to excellent yields.

     

Umpolung Synthesis of Diarylmethylamines via Palladium‐ Catalyzed Arylation of N‐Benzyl Aldimines

An umpolung synthesis of diarylmethylamine derivatives is presented. This reaction entails a palladium‐catalyzed arylation of 1,3‐diaryl‐2‐azaallyl anions, in situ generated from N‐benzyl aldimines. A Pd(NIXANTPHOS)‐based catalyst together with hindered silylamide bases enabled the coupling of aldimines with aryl bromides in good to excellent yields without product isomerization. Moreover, regioselectivity in the arylation of unsymmetrical 1,3‐diaryl‐2‐azaallyl anions was studied. This method is suitable for a gram scale synthesis of diarylmethylamine derivatives at room temperature without use of a glove box.

     

tert‐Butyl Sulfoxides: Key Precursors for Palladium‐Catalyzed Arylation of Sulfenate Salts

The present report describes an efficient and clean generation of sulfenate salts (R¹SO⁻) by pyrolysis of readily available tert‐butyl sulfoxides to give sulfenic acids (R¹SOH) and traceless isobutene, followed by hydrogen abstraction with a weak inorganic base (K₃PO₄). The relevance of this process was exemplified through an in situ palladium‐catalyzed cross‐coupling reaction with aryl halides/triflates leading to aryl sulfoxides. The operationally simple C S bond‐forming protocol developed uses Pd(dba)₂ as catalyst and Xantphos as ligand in toluene or a toluene/H₂O mixture. Further extensions include the use of di‐tert‐butyl sulfoxide as an equivalent for sulfur monoxide dianion (SO²⁻) and the development of diastereoselective versions in the [2.2]paracyclophane and biaryl series.