10.1002/ejoc.201901834
European Journal of Organic Chemistry
FULL PAPER
General procedure for the substrate scope of Buchwald-Hartwig reactions:
A 4 mL screw-capped vial was charged with 9.2 mg (0.01 mmol, 0.01
equiv.) Pd2(dba)3, 192.2 mg (2.0 mmol, 2.0 equiv.) NaOtBu and 8.4 mg
(0.02 mmol, 0.02 equiv.) Ligand (L1). The vial was purged with argon, and
2 mL toluene, 1.0 mmol (1.0 equiv.) halogenated compound and 1.25
mmol (1.25 equiv.) amine was added via septa. The reaction mixture was
stirred at 80 °C under argon atmosphere. After completion, the reaction
mixture was poured into 40 mL H2O and was extracted with 3×15 mL
CH2Cl2. The combined organic phases were washed with 2×10 mL 5 w/w%
NaHCO3 solution and 15 mL H2O, dried over MgSO4 and concentrated
under reduced pressure. The crude product was purified by column
chromatography on silica gel with hexane / ethyl acetate.
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General procedure for the coupling with tosylhydrazones: A 7ml screw-
capped vial was charged with 0.55 mmol (1.1 equiv.) tosylhydrazone, 2.3
mg (0.0025 mmol, 0.5 mol%) Pd2(dba)3, 0.005 mmol (1 mol%) ligand and
112 mg (1.4 mmol, 2.8 equiv.) LiOtBu, then purged with argon. 1.5 mL 1,4-
dioxane and 45 µL (2.5 mmol) water was added, followed by 0.5 mmol (1
equiv.) aryl halide and the vial was purged once again with argon. The
reaction mixture was placed into oil bath and stirred at 110°C, overnight.
After reaching full conversion the reaction mixture was diluted with 10 mL
DCM, the mixture was concentrated to celite and the product was isolated
with column chromatography (silica gel, eluent: hexane / ethyl acetate).
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Acknowledgements
R. J. Lundgren, B. D. Peters, P. G. Alsabeh, M. Stradiotto Angew.
Chem. Int. Ed. 2010, 49(24), 4071–4074.
János Bolyai Research Scholarship of the Hungarian Academy of
Sciences for Z.N., and support of National Research,
Development and Innovation Office (Grant No. KH125230) is
acknowledged. This work was completed in the ELTE Institutional
Excellence Program supported by the National Research,
Development and Innovation Office (NKFIH-1157-8/2019-DT).
The authors thank the Analytical Division at the Servier Research
Institute of Medicinal Chemistry for analytical measurements.
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Keywords: Palladium; Phosphine; Cross-coupling; Amination;
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TFA salts of the isolated ligands were prepared on 10 mg scale with
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were purified by preparative HPLC using a TFA containing eluent and
lyophilized
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