Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

• Anthony R. Martin,
• Anthony Chartoire,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2012, 8, 1637–1643, doi:10.3762/bjoc.8.187

• sterics of the aryl bromide had almost no impact on the reaction. Indeed, para-, meta- and ortho- substituted aryl bromides could be employed to arylate 6 in good yields. (Table 4, entries 1–3, 77–89%). However, ortho-disubstituted aryl bromide, such as bromomesitylene appeared to be too sterically

• demanding and led to no conversion (data not shown). Concerning the electronic properties of the aryl bromide, electron-withdrawing (EWG) and electron-donating groups (EDG) were tolerated, although the presence of EWGs resulted in decreased yields (Table 4, entries 4–6, 49–70%). The substrate 4

• sealed with a screw cap fitted with a septum. The heterocycle (0.6 mmol, 1.0 equiv) and/or the arylbromide (0.6 mmol, 1.0 equiv) were added at this point if in solid form, and DMA (1.9 mL) was poured into the vial. Outside of the glovebox, the heterocycle and/or the aryl bromide were added at this point

Synthesis of new pyrrole–pyridine-based ligands using an in situ Suzuki coupling method

• Matthias Böttger,
• Björn Wiegmann,
• Steffen Schaumburg,
• Peter G. Jones,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2012, 8, 1037–1047, doi:10.3762/bjoc.8.116

• information about the reaction conditions is given in Table 1. Reaction 1 of aryl bromide 8 to product 4 was repeated under the same conditions and with the same amounts of starting material and catalyst. The workup procedure was changed, which affected the yield only to a very small extent. In the original

• publication [11] the aryl bromide coupling partner was used in excess. As 19 is by far easier to prepare in large quantities, we altered the protocol and used it in excess, which produced even a slightly better yield than the other way round (Table 1). Finally, deprotection of 4 with hydrochloric acid after

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• group, after addition of the second aryl bromide [39]. A plausible mechanism for this cyclization/coupling reaction involves formation of intermediate 70 by reaction of the organopalladium complex with the newly formed γ-(N-arylamino)alkene 69. A syn-insertion of the alkene into the Pd–N bond in 70

• aryl bromide moiety 82, with primary amines and carbon monoxide, was developed by the same group [45]. The sequence involves first a selective palladium(0)-catalyzed amination on the Baylis–Hillman acetates with primary amines leading to allylic amines 83. This is followed by oxidative addition of the

• palladium species to the aryl bromide, which undergoes CO insertion to form the corresponding acylpalladium, which in turn is intercepted by the allylamine to give, after reductive elimination, the seven-membered ring lactams 84 in good to excellent yields. A wide range of amine components are compatible

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• fewer functional groups. Thus, methyl esters react rapidly with arylmagnesium reagents at 0 °C. In order to solve this problem, we have performed a Barbier-type preparation of aryl and heteroaryl zinc reagents by treating the aryl bromide or chloride with magnesium turnings in the presence of zinc

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• continuous stirring. The aryl bromide (15 mmol) and anhydrous cobalt bromide (330 mg) were then added to the mixture, which was stirred at rt for additional 20 min. Stirring was then stopped and the surrounding solution was taken-up with a syringe. The solution was then added to the flask containing the

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• synthesis of biological active molecules A typical example for the application of palladium-catalysed N-aryl bond formation is the synthesis of highly selective D3 receptor ligands 4. Piperazine (1) and a substituted aryl bromide 2 (Scheme 1) are coupled in the initial step of the synthesis. The electron

• -withdrawing substituents (nitrile and chloro) on the aryl bromide assisted the reaction, and reported yields of 3 are in the range of 65–90%. This method represents conditions from early catalyst generations and allowed the synthesis of a library of 18 compounds, which were investigated to identify a possible

• bromide and an acylated amine 51). In comparison to the Goldberg reaction conditions (CuI, NaH, DMF at 90 °C for 2 h), the change of the solvent to DME was crucial a gave good yields of up to 72% (Scheme 11). Additionally, the reaction was sensitive to the amount of NaH employed. Substituents on the aryl

A short and efficient synthesis of valsartan via a Negishi reaction

• Samir Ghosh,
• A. Sanjeev Kumar and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 27, doi:10.3762/bjoc.6.27

• -tetrazole (6) and its Negishi coupling with aryl bromide 5 are the key steps of the synthesis. This method overcomes many of the drawbacks associated with previously reported syntheses. Keywords: antihypertensive therapy; aryl bromide; Negishi coupling; tetrazole; valsartan; Introduction Valsartan (Figure

• important goal. In this paper, we report a new, concise and efficient synthesis of valsartan via Negishi coupling. Results and Discussion From a retro-synthetic analysis (Scheme 1), compound 8 could be constructed via Negishi coupling from aryl bromide 5 and 5-phenyl-1-trityl-1H-tetrazole (6), which in turn

• could be obtained from commercially available benzonitrile. Aryl bromide 5 could be accessed by several discrete reactions of compound 3 and compound 4 via a nucleophilic substitution reaction. As shown in Scheme 2, inexpensive and commercially readily available valeryl chloride 1 was coupled with L

Solvent-free and time-efficient Suzuki–Miyaura reaction in a ball mill: the solid reagent system KF–Al₂O₃ under inspection

• Franziska Bernhardt,
• Ronald Trotzki,
• Tony Szuppa,
• Achim Stolle and
• Bernd Ondruschka

Beilstein J. Org. Chem. 2010, 6, No. 7, doi:10.3762/bjoc.6.7

• results in Figure 1 are restricted to one aryl bromide (2a), experiments were expanded by taking into account the ability of the substituents to influence the experimental results. Figure 2 shows the results of blank tests regarding the base component, in which the C–C coupling was carried out in the

• ][39][40][41][42][57][58]. The yield of the coupling product depends on the reactivity of the aryl bromide and the reverse basicity of the SRS used. SRS1 (neutral γ-Al2O3) yielded the best results with the tested aryl bromides, followed by basic SRS2 (α-Al2O3) and SRS3 (γ-Al2O3). The preference of

• for 2b (SRS2a). The self-made supports SRS1a–3a show comparable results for each tested aryl bromide, except 2b. However, the results in Figure 4 are difficult to interpret regarding the influence of the different types of SRS used. The type of modification and the basicity of the initially applied

Gold film- catalysed benzannulation by Microwave- Assisted, Continuous Flow Organic Synthesis (MACOS)

• Gjergji Shore,
• Michael Tsimerman and
• Michael G. Organ

Beilstein J. Org. Chem. 2009, 5, No. 35, doi:10.3762/bjoc.5.35

• benzaldehydes [36] A 10 mL round-bottom flask was charged with Pd(PPh3)4 (0.0375 mmol), CuI (0.075 mmol), and purged with argon. To it were added consecutively: THF (6 mL), Et3N (1.5 mmol), the aryl bromide (0.75 mmol), and the alkyne (0.9 mmol). The solution was then heated to 70 °C and stirred for 6–13 h

From discovery to production: Scale- out of continuous flow meso reactors

• Peter Styring and
• Ana I. R. Parracho

Beilstein J. Org. Chem. 2009, 5, No. 29, doi:10.3762/bjoc.5.29

• we have been able to construct a viable alternative route that explains the observed by-products. Product scrambling occurs through trans-metallation between the intermediate nickel complex 3 formed by oxidative addition of the aryl bromide (Ar-Br), and the Grignard reagent. This results in the

• formation of the homo-coupled 4,4′-dimethoxybiphenyl by-product. Anisole (Ar-H) is formed by hydrodebromination of the aryl bromide via the same oxidative addition intermediate complex 3 due to the presence of traces of water in the system. This occurs both in the batch system, where there is only residual

• of whether or not a pre-wash is used. The induction is therefore most likely to be limited by adsorption of the aryl bromide onto the catalyst surface once catalyst activation is achieved. This is consistent with the Langmuir–Hinshelwood mechanism [17] for surface kinetics which depends on adsorption

A convenient catalyst system for microwave accelerated cross- coupling of a range of aryl boronic acids with aryl chlorides

• Matthew L. Clarke,
• Marcia B. France,
• Jose A. Fuentes,
• Edward J. Milton and
• Geoffrey J. Roff

Beilstein J. Org. Chem. 2007, 3, No. 18, doi:10.1186/1860-5397-3-18

• preferred procedure used 0.5 mmol of aryl halide and 0.75 mmol of boronic acid in 4–5 ml of solvent. In contrast to the mono-fluorinated phenyl boronic acids, 2,3,6-trifluorophenyl boronic acid failed to give appreciable amounts of product, even with an aryl bromide substrate (Table 1, Entries 15 and 16