Palladium-catalyzed Direct Arylation Research Articles

ChemInform Abstract: Efficient Synthesis and First Regioselective C‐3 Direct Arylation of Imidazo[1,2‐b]pyrazoles.

Highly regioselective: An efficient synthesis of the imidazo[1,2-b]pyrazole core has been developed, and the first regioselective palladium-catalyzed direct arylation of the C-3 position is described (see scheme). Good to excellent yields were obtained for a wide range of aryl partners with electron-rich and electron-poor substituents. This methodology allows rapid access to a large variety of imidazo[1,2-b]pyrazole products and could open the way to the design of new biologically active compounds.

ChemInform Abstract: Selective Palladium‐Catalyzed Direct Arylation of Furo[3,2‐b]pyridines.

AbstractThis describes the two‐step diarylation of furo[3,2‐b]pyridines in positions 3 and 7.

Synthesis of Heteroarylated Polyfluorobiphenyls via Palladium-Catalyzed Sequential sp2 C–H Bonds Functionalizations

The higher reactivity of C5-H bonds of heteroarenes as compared to C-H bonds of bromopolyfluorobenzenes for palladium-catalyzed direct arylation allows the selective synthesis of the polyfluoroaryl-heteroarenes in moderate to high yields, without C-H bond functionalization of the polyfluorobenzene ring. In most cases, low loading of Pd(OAc)2 catalyst (0.5-1 mol %) was employed. Then, from these heteroarylated polyfluorobenzenes, the palladium-catalyzed C-H bond functionalization of the polyfluorobenzene ring allows the synthesis of heteroarylated polyfluorobiphenyls.

Palladium-Catalyzed Direct Arylation of Methyl Sulfoxides with Aryl Halides

The palladium-catalyzed α-arylation of unactivated sulfoxides has been developed. The weakly acidic α-protons of sulfoxides are reversibly deprotonated by LiOtBu, and a palladium phosphine complex facilitates the arylation. A variety of aryl methyl sulfoxides were coupled with aryl bromides. More challenging coupling partners, such as alkyl methyl sulfoxides (including dimethyl sulfoxide) and aryl chlorides proved to be suitable under the optimized conditions. This method was utilized to synthesize bioactive benzyl sulfoxide intermediates.

Palladium-Catalyzed Direct Arylation of Chromium-Activated Benzylic C-H Groups

Correction to: Palladium-Catalyzed Direct Arylation of Chromium-Activated Benzylic C–H GroupsSynfacts 2013; 9(01): 0072-0072DOI: 10.1055/s-0032-1317756

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

New Pd–NHC complexes have been synthesized and employed for palladium-catalyzed direct arylation of pyrrole derivatives by using electron-deficient aryl chlorides as coupling partners. The desired coupling products were obtained in moderate to good yields by using 1 mol % of these air-stable palladium complexes. This is an advantage compared to the procedures employing air-sensitive phosphines, which have been previously shown to promote the coupling of aryl chlorides with heteroarenes.

Palladium-catalysed direct heteroarylation of bromobenzenes bearing SO2R substituents at C2 or C4

Palladium-catalysed direct arylation of 4- or 2-bromobenzenesulfonic acid derivatives in the presence of a variety of heteroaromatics was found to proceed using 0.1–0.5 mol% palladium acetate as the catalyst. However, both the nature and position of the SO2R substituent on such bromobenzenes has an influence on the reaction rates and yields. The presence of SO2Et or SO2NEt2 at the C2 or C4 position of bromobenzene is tolerated. Good results were also obtained from bromobenzene substituted at C4 by SO2NHPh or SO2OPh. On the other hand, the reactions of bromobenzenes bearing either SO2N(Me)CH2Ph or SO2OAr at C2 led in some cases to intramolecular reactions instead of the desired intermolecular couplings. Some reactions were performed in cyclopentyl methyl ether, which can be considered as a green solvent.

Palladium-catalyzed para-selective arylation of phenols with aryl iodides in water

Highly para-selective palladium-catalyzed direct arylation of phenols with aryl iodides was demonstrated by taking advantage of the formal inverse direct arylation strategy. A series of 4-aryl phenols were synthesised by employing water as a "green" solvent under mild reaction conditions.

A straightforward access to guaiazulene derivatives using palladium-catalysed sp2 or sp3 C–H bond functionalisation

A novel palladium-catalysed direct arylation of guaiazulenes with a variety of aryl bromides is reported. Both sp(2) and sp(3) C-H bonds have been functionalised, as the nature of the cation of the base was found to allow the control of the regioselectivity of the arylation giving rise to C2 or C3 arylated guaiazulenes and also to 4-benzylguaiazulenes.

Direct Arylation of meso‐Formyl Porphyrin

Palladium-catalyzed direct arylation of meso-formyl Ni(II) porphyrin with aryl bromides provided β-monoarylated meso-formyl porphyrins. In spite of the existence of the meso-formyl group, the reactions proceeded regioselectively at the β-position adjacent to the formyl group. β-Arylated formyl porphyrin was converted to a tetraline-fused porphyrin by reduction and subsequent acid-catalyzed cyclization and to a meso-meso vinylene-bridged diporphyrin by McMurry coupling (see scheme).

ChemInform Abstract: Palladium‐Catalyzed Direct Arylation of 5‐Chloropyrazoles: A Selective Access to 4‐Aryl Pyrazoles.

AbstractA number of 4‐arylated pyrazoles can be prepared efficiently.

Palladium-Catalyzed Direct Arylation of Chromium-Activated Benzylic C–H Groups

Palladium-Catalyzed Direct Arylation of Chromium-Activated Benzylic C–H Groups

Efficient Synthesis and First Regioselective C‐3 Direct Arylation of Imidazo[1,2‐b]pyrazoles

Highly regioselective: An efficient synthesis of the imidazo[1,2-b]pyrazole core has been developed, and the first regioselective palladium-catalyzed direct arylation of the C-3 position is described (see scheme). Good to excellent yields were obtained for a wide range of aryl partners with electron-rich and electron-poor substituents. This methodology allows rapid access to a large variety of imidazo[1,2-b]pyrazole products and could open the way to the design of new biologically active compounds.

Palladium-catalysed direct arylations of heteroaromatics bearing dicyanovinyls at C2

The palladium-catalysed direct 5-arylation of heteroaromatics bearing dicyanovinyls at C2 with aryl bromides via C–H bond functionalisation allows the synthesis of a variety of new conjugated systems in only one step. The nature of the solvent was found to be crucial to perform such arylations. In DMAc, complete decomposition of the dicyanovinyl derivatives was observed, whereas they were found to be stable in cyclopentyl methyl ether.

Phosphine-Free Palladium-Catalyzed Direct C-3 Arylation of 2-Phenylimidazo[1,2-a]pyridine Using Silver(I) Carboxylate

Phosphine-free palladium-catalyzed direct arylation of 2-phenyl-imidazo[1,2-a]pyridine has been developed with the concept of using silver(I) carboxylate. This protocol efficiently catalyzes the C-H arylation of 2-phenyl-imidazo[1,2-a]pyridine with aryl iodides to afford the corresponding 2-phenyl-3-aryl-imidazo[1,2-a]pyridines in moderate to-good yields.

Palladium-Catalyzed Direct Arylation of 5-Chloropyrazoles: A Selective Access to 4-Aryl Pyrazoles

The use of a temporary protection by a chloro group at C5 of pyrazoles allows the synthesis of the 4-arylated pyrazoles, which were previously inaccessible by palladium-catalyzed direct arylation, with complete regioselectivity and in high yields using in most cases as little as 0.5-0.1 mol % Pd(OAc)(2) as the catalyst with electron-deficient aryl bromides. Moreover, from 5-chloro-1,3-dimethylpyrazole, sequential catalytic C4 arylation, dechlorination, catalytic C5 arylation reactions allowed the synthesis of a 4,5-diarylated pyrazole derivative.

Palladium-Catalysed Direct Heteroarylations of Heteroaromatics Using Esters as Blocking Groups at C2 of Bromofuran and Bromothiophene Derivatives: A One-Step Access to Biheteroaryls

Methyl 5-bromo-2-furoate and ethyl 5-bromothiophene-2-carboxylate have been found to be useful alternative reagents to 2-halofurans and 2-halothiophenes for the palladium-catalysed direct arylation of heteroaromatics. As their C5 is blocked by ester groups, the use of these substrates prevents the formation of dimers or oligomers, and therefore allows the formation of biheteroaryls in high yields. A very wide variety of heteroaromatics can be coupled with these two reagents. Moreover, with methyl 5-bromo-2-furoate, sequential catalytic C5 arylation, decarboxylation, catalytic C2-arylation reactions allowed the synthesis of 2,5-diarylated furan derivatives.

Solvent‐Free Palladium‐Catalyzed Direct Arylation of Heteroaromatics with Aryl Bromides

Solvent is one of the major sources of waste in the course of catalyzed direct arylations. Some palladium-catalyzed direct arylations of heteroaromatics can be advantageously performed without any solvent. In the presence of palladium catalysts (1 mol %) and potassium acetate as the base, the direct 5-arylation of some thiazoles, thiophenes, furans, or pyrroles with aryl bromides as coupling partners proceeds highly regioselectively and in moderate to high yields. However, the use of these solvent-free conditions is limited to electron-deficient aryl bromides.

Palladium-catalyzed direct arylation using free NH2 substituted thiophene derivatives with inhibition of amination type reaction

The palladium-catalyzed direct arylation at C2 or C5 of free NH2 substituted thiophene derivatives was found to proceed in moderate to high yields using a variety of aryl halides. The choice of potassium acetate as the base was found to be crucial to inhibit the amination reaction and to promote the direct arylation.

Reactivity and Regioselectivity of Palladium-Catalyzed Direct Arylation in Noncooperative and Cooperative Processes

Recent discovery (J. Am. Chem. Soc 2012, 134, 3683) of the involvement of the cyclometalated [Pd (tBu2PCMe2CH2)(OAc)]2 complex in direct arylation of pyridine N-oxide suggested that the mechanism of this reaction may involve a process in which C–H activation occurs at one Pd center and the aryl group undergoes coupling with another aryl group at a second Pd center (a cooperative catalysis). In this work, cleavage of arene C–H bonds of different (hetero)arenes via a concerted metalation–deprotonation (CMD) pathway was evaluated for both noncooperative and cooperative processes so that the two processes could be compared in terms of reactivity and regioselectivity. The distortion–interaction analysis was performed to quantify the various contributions to the CMD transition states. Calculated barriers of the C–H bond cleavage in the two processes indicate that the cooperative and noncooperative processes lead to the same regioselectivity of arylation. Differences in contributions to the activation barriers between the two processes are fairly minor. This allows us to use the existing data about (hetero)arene C–H reactivity and regioselectivity in the noncooperative arylation and apply it to predict reactivity and regioselectivity of arylation in the cooperative process.