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Arylboration of Enecarbamates for the Synthesis of Borylated Saturated N-Heterocycles
Grace L. Trammel ; Prashansa B. Kannangara ; Dmytro Vasko , et al. Angew. Chem. Int. Ed.,2022,61,e20221211. DOI: 10.1002/anie.202212117 PubMed ID: 36250954
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Abstract: Two catalytic systems have been developed for the arylboration of endocyclic enecarbamates to deliver synthetically versatile borylated saturated Nheterocycles in good regio- and diastereoselectivities. A Cu/Pd dual catalytic reaction enables the synthesis of borylated, α-arylated azetidines, while a Ni-catalysed arylboration reaction efficiently functionalizes 5-, 6-, and 7-membered enecarbamates. In the case of the Cu/Pdsystem, a remarkable additive effect was identified that allowed for broader scope. The products are synthetically useful, as demonstrated by manipulations of the boronic ester to access biologically active compounds.
Keywords: Alkene ; Arylation ; Boron ; Cross Coupling ; Heterocycle
Purchased from AmBeed: 100367-39-3 ; 66899-02-3 ; 3964-04-3 ; 108963-96-8
CAS No. : | 100367-39-3 | MDL No. : | MFCD08277268 |
Formula : | C6H6BrNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YFTGMMXMLPTTAY-UHFFFAOYSA-N |
M.W : | 188.02 | Pubchem ID : | 14062309 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate; In dimethyl sulfoxide; | a) 4-(2-Chloro-4-methoxyphenyl)-2-methoxypyridine A mixture of 4-bromo-2-methoxypyridine (1.20 g, 6.38 mmol), <strong>[219735-99-6]2-chloro-4-methoxyphenylboronic acid</strong> (2.38 g, 12.8 mmol), and potassium carbonate (2.65 g, 19.1 mmol) in anhydrous DMSO (12 mL) was degassed for several minutes with argon. Dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (261 mg, 0.32 mmol) was added and, after degassing briefly with argon again, the flask was sealed, and the reaction was heated to 90 C. and stirred for 2 h. After cooling to rt, the reaction mixture was diluted with ethyl acetate, washed with 5% lithium chloride solution (4*), dried over sodium sulfate, filtered, and concentrated. Flash chromatography (80 g ISCO Gold column, 2%-20% ethyl acetate/hexanes) provided the title compound (1.51 g, 95%) as a white solid: 1H NMR (500 MHz, CDCl3) delta 8.19 (d, J=5.0 Hz, 1H), 7.24 (d, J=8.5 Hz, 1H), 7.02 (d, J=2.0 Hz, 1H), 6.96 (d, J=5.0 Hz, 1H), 6.88 (dd, J=8.3, 2.3 Hz, 1H), 6.08 (s, 1H), 3.98 (s, 3H), 3.84 (s, 3H); ESI MS m/z 250 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃; | To a solution of II (2.00 g, 10.6 mmol) in DMF (21 mL) was added NCS (2.98 g, 22.3 mmol). The reaction mixture was stirred at rt overnight. The reaction mixture was quenched with water, diluted with EtOAc, and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried over MgS04, and concentrated. The crude product was purified by silica chromatography to provide 1J (2.15 g, 9.18 mmol, 86percent yield) as a white solid. LC-MS Anal. Calc'd for C6H5BrClNO: 220.92, found [M+H] 223.8. 1H NMR (400 MHz, CDC13) delta 8.15 (s, 1H), 7.05 (s, 1H), 3.91 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.9% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In dimethyl sulfoxide; at 95℃; | To a solution of compound 1 (2.0g, leq) in DMSO were added compound 2 (1 g, leq), PdC idppf) (0.77 g, O.leq) and K2C03(2.9g, 2eq). The mixture was stirred at 95 C overnight. The reaction was quenched by water, and worked up under standard procedure. The residue was purified by flash column chromatography to give the title compound (2.1 g, yield: 78.9%). |
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