Carbonates: Ecofriendly Solvents for Palladium-Catalyzed Direct 2-Arylation of Oxazole Derivatives (original) (raw)
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Studies on Palladium-Catalyzed Benzylic Arylation
2009
Contents General Introduction Chapter 1 Palladium-Catalyzed 2-Pyridylmethyl Transfer from 2-(2-Pyridyl)ethanol Derivatives to Organic Halides by Chelation-Assisted Cleavage of Unstrained sp 3 C-sp 3 C Bonds Chapter 2 Palladium-Catalyzed Direct Arylation of Aryl(azaaryl)methanes with Aryl Halides Providing Triarylmethanes Chapter 3 Palladium-Catalyzed Benzylic Arylation of N-Benzylxanthone Imine Chapter 4 Palladium-Catalyzed Benzylic Direct Arylation of Benzyl Sulfone Publication List Acknowledgment tol tolyl Xantphos 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene Halogen-magnesium exchange Cross-homo scrambling Scheme 6. Br Br m 1 mol% Pd(PPh 3) 4 + Br m = MgCl, Et 2 O, reflux, 20 h m = ZnBr, THF, 50 ˚C, 16 h 20% 68% Scheme 7. X Mg metal MgX + Undesirable dimerization Scheme 5. General Introduction derivative in 22% yield. Because organoboron compounds are generally synthesized via hydroboration, benzylboron compounds are less readily available and are uncommon coupling partners in Suzuki-Miyaura cross-coupling reaction. Flaherty et al. reported the palladium-catalyzed benzylation of aryl halides with commercially available benzylboron compounds (Scheme 9). 11 As described above, benzylzinc derivatives appear to be the most favorable benzylmetals in all respects for palladium-catalyzed benzylation. Although palladium-catalyzed cross-coupling reactions of benzylzincs display high reactivity and chemoselectivity, the need still exists for preparation of benzylzinc reagents by treatment of benzyl halides with a stoichiometric amount of Zn powder. Furthermore, synthesis of benzyl halides often requires several steps. An alternative attractive route for the palladium-catalyzed benzylation of aryl halides is the use of stable organic compounds bearing no metallic atom as nucleophilic partners (Scheme 10).
Efficient palladium-catalyzed coupling reactions of aryl bromides and chlorides with phenols
Chemical Communications, 2009
Experimental section: Reagents: All reagents were purchased from Aladdin Reagent Company and Alfa-Aesar Company without further purification. Toluene and dioxane were purified by distillation though a standard procedure. Analytical Methods: 1 H-NMR and 13 C-NMR spectra were recorded on a Bruker 300 MHz instrument with chemical shifts reported in ppm relative to the residual deuterated solvent or the internal standard tetramethylsilane. Gas chromatography analyses were performed on a Hewlett Packard 5890 instrument with a FID detector and Hewlett Packard 24 m x 0.2 mm i.d. HP-5 capillary column. Yield refers to isolated yields of compounds greater than 95% purity as determined by capillary gas chromatography (GC) and proton Nuclear Magnetic Resonance spectroscopy (1 H-NMR) analysis. General procedure for the Pd-catalyzed synthesis of diaryl ethers from aryl halides with phenols. All reactions were carried out under an argon atmosphere in schlenk tubes (containing a stir bar). A schlenk tube containing a stir bar was charged with Pd(OAc) 2 (2.0 mol% Pd), ligand (6.0 mol%) and K 3 PO 4 (2.0 equiv.). If the aryl halides (1.0 mmol) and/or phenols (1.2 equiv.) were solids, they were also added at this time. The tube was evacuated and backfilled with argon (this sequence was repeated three times). If the aryl halides and/or phenols were liquids, they were added to the tube at this time along with the solvents. The mixture was stirred in a preheated oil bath (80-100°C) until the aryl halide was consumed as judged by TLC or GC analysis (10-24 h, reaction times were not optimized). The crude material was purified by column chromatography on silica gel (eluting with ethyl acetate/hexane or diethyl ether/hexane mixtures). 1-(4-Phenoxyphenyl)ethanone 1 : The crude material was purified by flash chromatography column on silica gel (10:1 ethyl acetate/hexane) to afford the title compound as a white solid. M.p.
Carbonates: eco-friendly solvents for palladium-catalysed direct arylation of heteroaromatics
Green Chemistry, 2010
The palladium-catalysed direct 2-, 4-or 5-arylation of a wide range of heteroaromatics with aryl halides proceed in moderate to good yields using the eco-friendly solvents carbonates. The best yields were obtained using benzoxazole or thiazole derivatives. The arylation of furan, thiophene, pyrrole, imidazole or isoxazole derivatives was found to require a more elevated reaction temperature.
Catalytic C–C coupling through C–H arylation of arenes or heteroarenes
Coordination Chemistry Reviews, 2010
with bromobenzene in the presence of Pd(OAc) 2 /PPh 3 as catalyst with Cs 2 CO 3 as a base in refluxing o-xylene for 32 h gave 2-biphenyl-6-terphenylphenol in 58% yield. One of the possible pathways is shown below in Scheme 11. Benzyl alcohols, acetophenones, benzyl phenyl ketones, anilides [9] and benzaldehydes [66] could be arylated analogously in ortho positions. Aliphatic carbons of acetophenones and benzyl phenyl ketones were also arylated. [9] Scheme 11. The mechanism seems to correspond to an electrophilic substitution assisted by chelation (Scheme 12). This is in accord with the transition state proposed for electrophilic attack on phenols. [67] Scheme 12. Two methods for direct o-arylation of benzoic acids with aryl iodides or bromides have been proposed by Daugulis: the first employs stoichiometric amounts of silver acetate for iodide 11 removal from aryl iodide in acetic acid at 130 °C; the second, suitable for aryl chlorides, uses n-butyl-di-1-adamantylphosphine ligand in DMF at 145 °C. [68] 4.2 Arene C-H Arylation Directed by Heteroatoms The attack of bromobenzene on the 2-position of furan has been recognized since 1985 [53] (Scheme 13) but only more recently a methodology of broader scope has been worked out. Scheme 13. A number of heterocycles can now be arylated selectively using palladium and rhodium catalysts. Beside furans, [69] several types of heterocycles such as pyrroles, [70] indoles, [70,71] thiophenes, [9] oxazoles, [72] thiazoles, [50] imidazoles, [73] indolizines [74] have been reported to undergo selective arylation. [9] Scheme 14 shows some examples using different heterocyclic substrates, aryl halides (iodides, bromides, chlorides), catalysts, bases and additives. Scheme 14. Indoles offer an interesting example of reactivity at two positions (C-2 and C-3). See for examples the first and second equation of Scheme 14. Reactivity at C-3 was obtained in the presence of phosphinous acids as ligands for palladium [71] while phenylation at the C-2 position occurred in the presence of Pd(OAc)2/PPh3. [75] Sames et al. rationalized this behavior 12 in the framework of the electrophilic substitution mechanism. Position C-3 is the preferred one, but if proton removal from the initial palladium complex is slow, there is time for a metal migration from C-3 to C-2 and arylation of the latter may occur exclusively. [75] Indole research has been reviewed. [76] In the presence of PdCl2(PPh3)2 and under the conditions reported in the third equation indolizine readily reacts with bromobenzene to afford the C-3 phenylated derivative in 71% yield. The reaction is compatible with a variety of substituents both on the indolizine and aryl halide. [74] The use of AgNO3/KF at 150°C allowed Pd-catalyzed arylation of 2-bromothiophenes with aryl iodides without affecting the Br-C bond. [74c] Aryl chlorides can arylate benzothiazole (fourth equation of Scheme 14) under the catalytic action of palladium in the presence of bulky, electron-rich phosphine ligands such as n-BuAd2P (Ad = adamantyl), which gives the best results. The methodology is applicable to a variety of electron-rich heterocycles and aryl chlorides. [72b] Selectivities in cross-coupling of azoles with two or more heteroatoms is discussed in a review. [77] Direct arylation of 1,2,3-triazole can be performed under palladium [78,79] and copper [80] catalysis. Selective arylations at the 2-and 5positions of azoles were achieved by varying the palladium-based catalytic system. For example CuI addition directed arylation towards position 2 of both N-methylimidazole and thiazole, while in the absence of CuI the 5-position was preferred. [81] Sames and coworkers found that some SEM-protected pyrazoles (SEM = 2-(trimethylsilyl)ethoxymethyl) could be arylated selectively at the 5-position and sequentially in the 3-position after SEM shift to the other nitrogen in the presence of palladium acetate, P(n-Bu)Ad2 and potassium pivalate at 140 °C in DMA. The deprotonation mechanism proposed by Fagnou [18,19,82] may be here at work to explain the preferential reactivity of the more acidic 5-position. [83] In some cases it has been shown that a deprotonation with ring opening is involved. Benzoxazoles open up the oxazole ring forming a palladium-coordinated isocyanophenolate. [84] The reaction occurs at 120 °C using Pd(OAc)2/PPh3, Cs2CO3 in DMF for 1 h. A proton abstraction mechanism has been suggested to be at work as shown in Scheme 15. A similar mechanism has been shown to be operative for 2-metalated thiazoles and imidazoles. [85] 13 Scheme 15. Thiophenes, furans, pyrroles and indoles could be arylated with a rhodium catalyst containing P[OCH(CF 3) 2 ] 3 as ligand. 3-Methoxythiophene was diarylated by iodobenzene selectively at carbons adjacent to sulfur to afford 2,5-diphenyl-3-methoxythiophene in 79% yield (Scheme 16). The reaction was over in 30 min when carried out in m-xylene at 200 °C under microwave irradiation. [86] The reaction was also extended to arene derivatives. Experimental data are consistent with an electrophilic mechanism. [87] Scheme 16. Rhodium-catalyzed arylation of benzimidazole in the presence of 9-cyclohexylbicyclo[4.2.1]-9-phosphanonane (cyclohexylphobane) was achieved by direct coupling of benzimidazole with aryl iodides and bromides bearing a wide variety of functional groups in good yields under microwave conditions (250 °C). [88] Miura and coworkers described several procedures in which arene and heteroarene C-H [6] and CC [9] activation are intertwined. We deem it useful to deal first with the general process of arene arylation reported in Scheme 17 for ,-disubstituted arylmethanols, which can be traced to both type of activation, the former product coming from OH assisted C-H arylation and the latter from CC bond cleavage with concomitant ketone formation (involving hydroxyl palladation). [89] 14 Scheme 17. The reaction of 2-phenyl-2-propanol with bromobenzene gave rise to mono-, di-and triphenylated products as shown in Scheme 18. The first two products result from arylation via CC bond cleavage, while the others from OH assisted C-H arylation. Selectivation towards the former products (essentially the monoarylated one) can be achieved using triphenylmethanol in place of 2-phenylpropanol and a bulky phosphine such as PCy 3. This also enables aryl chlorides to react efficiently. [89] Scheme 18. Passing to a heterocyclic substrate such as thiophene, the CR 2 OH group was readily removed from the 3-position and replaced by a phenyl group after aryl attack on position 2. A third phenyl group attacked position 5 more slowly. Thus, as reported in Scheme 19, ,-diphenyl-3-thiophenemethanol and bromobenzene were converted into 2,3-diphenylthiophene in 86% yield. Only a minor amount (10%) of 2,3,5-triphenylthiophene was formed. [90]
ChemInform, 2002
The reaction of o-ethynylphenols 3 with a wide variety of unsaturated halides or triflates 6 in the presence of Pd(OAc) 2 (PPh 3 ) 2 , CuI, and Et 3 N (procedure A) gives 2-vinyl-and 2-arylbenzo[b]furans 7, in good to high yield, through a palladium-catalyzed coupling followed by an in situ cyclization step. Small amounts of 2,3-disubstituted-benzo[b]furans 8 are usually isolated as side products. In some cases, however, compounds 8 are generated in significant yield or even as the main products. The formation of 8 can be prevented by employing alternative procedures (B and C) that use o-((trimethylsilyl)ethynyl)phenyl acetates 5 as starting building blocks. Procedure B is based on the palladium-catalyzed reaction of 5 with 6 in the presence of Pd(PPh 3 ) 4 , Et 3 N, and n-Bu 4 NF, followed by the hydrolysis of the resultant coupling derivative 12 under basic conditions. Procedure C affords 7 through an in situ coupling/cyclization of 5 with 6 in the presence of Pd(PPh 3 ) 4 and KOBu t . The utilization of o-alkynylphenols 9 as the starting alkynes in the palladium-catalyzed reaction with 6 leads to the formation of 2,3-disubstituted-benzo[b]furans 13 through an annulation process promoted by σ-vinyl-and σ-arylpalladium complexes generated in situ. The best results in this case are obtained by using KOAc and Pd(PPh 3 ) 4 . In the presence of KOAc and Pd(PPh 3 ) 4 , and under an atmosphere of carbon monoxide, the reaction of o-alkynylphenols with 6 provides 2-vinyl-and 2-aryl-3-acylbenzo[b]furans 14.
Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series
Beilstein Journal of Organic Chemistry, 2011
Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki–Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented.
Chemistry – A European Journal, 2011
A new ferrocenyl triphosphane ligand associated to palladium was found to be an efficient catalyst for the direct coupling of highly congested, functionalised aryl bromides with a variety of heteroarenes. These coupling reactions can generally be performed by using a low‐loading (0.1–0.5 mol %) of the catalyst. The present protocol tolerates important and useful functional groups, which allows for further elaboration into more sophisticated heterocyclic molecules. The straightforward arylation of heteroaromatic compounds with congested ortho‐substituted aryl bromides may permit further convergent syntheses of diverse ligands, biologically active molecules and molecular materials in only a few steps.
Cheminform, 2010
The reaction of o-ethynylphenols 3 with a wide variety of unsaturated halides or triflates 6 in the presence of Pd(OAc) 2 (PPh 3 ) 2 , CuI, and Et 3 N (procedure A) gives 2-vinyl-and 2-arylbenzo[b]furans 7, in good to high yield, through a palladium-catalyzed coupling followed by an in situ cyclization step. Small amounts of 2,3-disubstituted-benzo[b]furans 8 are usually isolated as side products. In some cases, however, compounds 8 are generated in significant yield or even as the main products. The formation of 8 can be prevented by employing alternative procedures (B and C) that use o-((trimethylsilyl)ethynyl)phenyl acetates 5 as starting building blocks. Procedure B is based on the palladium-catalyzed reaction of 5 with 6 in the presence of Pd(PPh 3 ) 4 , Et 3 N, and n-Bu 4 NF, followed by the hydrolysis of the resultant coupling derivative 12 under basic conditions. Procedure C affords 7 through an in situ coupling/cyclization of 5 with 6 in the presence of Pd(PPh 3 ) 4 and KOBu t . The utilization of o-alkynylphenols 9 as the starting alkynes in the palladium-catalyzed reaction with 6 leads to the formation of 2,3-disubstituted-benzo[b]furans 13 through an annulation process promoted by σ-vinyl-and σ-arylpalladium complexes generated in situ. The best results in this case are obtained by using KOAc and Pd(PPh 3 ) 4 . In the presence of KOAc and Pd(PPh 3 ) 4 , and under an atmosphere of carbon monoxide, the reaction of o-alkynylphenols with 6 provides 2-vinyl-and 2-aryl-3-acylbenzo[b]furans 14.