Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• trifluoromethylation of vinyl triflates and nonaflates (Scheme 65). A variety of trifluoromethylated cyclohexenes were obtained using a catalyst system, which was composed of Pd(dba)2 or [(allyl)PdCl]2 and the monodentate biaryl phosphine ligand t-BuXPhos. Also, TMSCF3 and KF were more suitable to the

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• purified and characterized or, for further transformations, the crude products are directly converted into the corresponding nonaflates by deprotonation with sodium hydride and treatment with 1-nonafluorobutanesulfonyl fluoride (NfF). Scheme 13 shows two examples, PM52 and PM54 that are ready for palladium

• -catalyzed reactions. As mentioned above, pyridyl nonaflates derived from the β-ketoenamides KE are excellent substrates for palladium-catalyzed coupling reactions as briefly discussed in our review [23]. Pyrimidyl nonaflates can analogously be used to achieve higher substitution degrees as illustrated by

• PM50; (NMO = N-methylmorpholine N-oxide). Deprotection of 5-alkoxy-substituted pyrimidines PM2, PM20 and PM29 and conversion into nonaflates PM52 and PM54; (Nf =1-nonafluorobutanesulfonyl). Palladium-catalyzed coupling reactions of PM54 and PM12 giving rise to new pyrimidine derivatives PM55–58

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• [21][22]. We previously reported the synthesis of enantiopure 1,2-oxazin-4-yl nonaflates and phosphates starting from precursors of type 3 and their conversion into differently C-4-substituted products employing palladium-catalyzed cross-coupling reactions [23]. In a related study, we have also

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• -nonaflation employing nonafluorobutanesulfonyl fluoride provided the expected 4-nonafloxy-substituted bipyridine derivatives 5a–g in moderate to good overall yields. The bipyridyl nonaflates are excellent precursors for palladium-catalyzed reactions as demonstrated by representative Suzuki and Sonogashira

• couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. Keywords: 2,2-bipyridines; cross couplings; cyclocondensation; β-ketoenamides; nonaflates; Introduction In 2009

• employing hydroxylamine hydrochloride [51][52]. These products of simple condensation reactions may be regarded as azabipyridine derivatives and their synthesis demonstrates the versatility of β-ketoenamide such as 3i for the synthesis of highly functionalized heterocycles. The 2,2´-bipyridyl nonaflates

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• gave lower yields and longer reaction times were required to compensate for the use of the less reactive diphenyltrimethylsilylphosphine. Lipshutz et al. used a Pd(0) catalyst to synthesize triarylphosphine boranes by coupling secondary diphenylphosphine borane 13e with aryl nonaflates or triflates

• -catalyzed phosphination of aryl triflates and nonaflates instead of aryl iodides with phosphine boranes [158]. The first examination towards an enantioselective C–P cross-coupling starting from racemic secondary phosphine boranes was performed by Gaumont and Pican [175]. The highest enantiomeric excess

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• the range of 60–72%. Pyrid-4-yl nonaflates are excellent precursors for transition metal-catalyzed cross-coupling reactions [42][54][55][56][57][58], which was demonstrated here by the successful Suzuki coupling of bisnonaflate 19 with (E)-styrylboronic acid and the Stille coupling of 19 with 2

• column chromatography (silica gel, EtOAc) to provide bis(4-hydroxypyridine) 18a (0.174 g, 60%) as a brown liquid and 18b (54 mg, 18%) as pale yellow oil. The products were directly converted into the corresponding nonaflates 19 and 20. Nonaflation of 4-hydroxypyridines (typical procedure 3) Bis(4

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• system to convert cyclic vinyl triflates or nonaflates to their trifluoromethylated equivalents (Table 4) [66]. Ruppert’s reagent was used as the CF3– precursor in a combination with potassium fluoride as an activator for the reaction with vinyl triflates, while TESCF3 and rubidium fluoride gave better

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• substrate scope and leads to differentially substituted enantiopure pyridines in good to moderate yields. The preparation of diverse substituted lactic acid derived pyrid-4-yl nonaflates is described. Additional evidence for the postulated mechanism of the multicomponent reaction is presented. Keywords

• : allenes; enantiopure pyridines; ketoenamides; multicomponent reactions; nonaflates; Introduction The pyridine core is ubiquitous in pharmacologically active agents, agrochemicals and natural products [1][2][3][4][5]. The HMG-CoA reductase inhibitors Glenvastatin and Cerivastatin are exemplarily mentioned

• nonaflates are excellent coupling partners in palladium-catalyzed transformations such as Suzuki, Stille, Heck and Sonogashira reactions [45]. However, in contrast to the smooth nonaflation, the selective O-alkylation of the synthesized pyridines turned out to be more challenging (Scheme 5). Whereas pyridone

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• nonaflates [53], Grignard reagents with dihalobenzenes [54][55][56]: Other methods give poor yields. The Suzuki cross coupling protocol has been used for the synthesis of terphenyls and polyaryls using Pd(OAc)2 or Pd(PPh3)4 with or without ligands in homogeneous medium [57][58][59][60]. Although, these

Preparation of pyridine-3,4-diols, their crystal packing and their use as precursors for palladium-catalyzed cross-coupling reactions

• Tilman Lechel,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 42, doi:10.3762/bjoc.6.42

• plane with two pyridinone molecules in a perpendicular plane. The two alternating planes are connected by hydrogen bridges. As a consequence of our ongoing interest in perfluoroalkyl sulfonate chemistry [25], we converted the two hydroxyl groups into triflates or nonaflates, respectively (Scheme 2

• possible palladium-catalyzed cross-couplings we performed several Sonogashira-reactions [28][29][30]. As described in Scheme 3, the pyridinyl-bistriflates or -nonaflates 3 were coupled with alkynes like phenylacetylene or (triisopropylsilyl)acetylene using Pd(PPh3)4 or alternatively, Pd(OAc)2/PPh3 as

• of 3-alkoxypyridinols 1 to pyridine-3,4-diols 2. aMethod a: Pd/C, H2, MeOH, rt, 1 d; bMethod b: BBr3, CH2Cl2, 0 °C to rt, 1 d; cMethod c: TFA:CH2Cl2 (1:2), rt, 1 h. Conversion of pyridine-3,4-diols 2 into pyridinediyl bistriflates or -nonaflates 3. a) Et3N, Rf2O, CH2Cl2, 0 °C to rt, 1 d. Sonogashira