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Highly selective catalytic transfer hydrodeuteration of cyclic alkenes
Hintzsche, Samuel J. ; Vang, Zoua Pa ; Rivera Torres, Emanuel , et al. J. Labelled Compd. Rad.,2023,66(3):86-94. DOI: 10.1002/jlcr.4015 PubMed ID: 36772856
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Abstract: Selective deuterium installation into small molecules is becoming increasingly desirable not only for the elucidation of mechanistic pathways and studying biological processes but also because of deuterium's ability to favorably adjust the pharmacokinetic parameters of bioactive molecules. Fused bicyclic moieties, especially those containing heteroatoms, are prevalent in drug discovery and pharmaceuticals. Herein, we report a copper-catalyzed transfer hydrodeuteration of cyclic and heterocyclic alkenes, which enables the synthesis of chromans, quinolinones, and tetrahydronaphthalenes that are precisely deuterated at the benzylic position. We also demonstrate the ability to place one deuterium atom at the homobenzylic site of these scaffolds with high regioselectivity by swapping transfer reagents for their isotopic analogs. Furthermore, examples of chemoselective transfer hydrogenation and transfer deuteration are disclosed, allowing for the simultaneous incorporation of two vicinal hydrogen or deuterium atoms into a double bond.
Keywords: copper ; deuteration ; hydrodeuteration ; hydrogenation ; transition metal catalysis
Purchased from AmBeed: 6836-19-7 ; 14243-64-2 ; 19315-93-6 ; 1810-66-8 ; 584-08-7 ; 189114-61-2 ; 447-53-0
CAS No. : | 14243-64-2 | MDL No. : | MFCD00009588 |
Formula : | C18H15AuClP | Boiling Point : | - |
Linear Structure Formula : | [Au(P(C6H5)3)(Cl)] | InChI Key : | IFPWCRBNZXUWGC-UHFFFAOYSA-M |
M.W : | 494.71 | Pubchem ID : | 10874691 |
Synonyms : |
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Chemical Name : | Chloro(triphenylphosphine)gold(I) |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501 | 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 |
---|---|---|
96% | With sodium ethanolate; In ethanol; at 20.0℃; for 17.0h; | Under an argon atmosphere, Au(PPh3)Cl (0.20 g, 0.40 mmol), <strong>[103987-81-1]8-quinolylethyne</strong> (92 mg, 0.60 mmol) and ethanol (8 ml) were added to a Schlenk tube (25 mL) and sodium ethoxide (165 mul, 0.42 mmol; 2.55 M, ethanol solution) was added dropwise thereto, followed by stirring of the mixture at room temperature for 17 hours. After completion of the reaction, the resulting white precipitate was filtered and washed with ethanol (5 ml×three times), water (5 ml×four times) and ethanol (5 ml×three times) and dried under vacuum to give 0.23 g of the desired compound as a pale yellow powder (yield: 96%). 1H-NMR (400MHz, CDCl3) delta: 9.07 (dd, 1H), 8.12 (dd, 1H), 7.99 (dd, 1H), 7.68 (dd, 1H), 7.62-7.36 (m, 17H) 31P-NMR (160 MHz, CDCl3): 42.8 FAB-MS (M/Z) : 612 (M+H)+ Luminescence analysis: (CHCl3, 77K, Ex250nm) lambda (nm): 380, 526, 567 Elemental analysis: Found C: 57.06, H: 3.45, N: 2.33 Theoretical C: 56.97, H: 3.46, N: 2.29 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium ethanolate; In ethanol; at 20℃; for 17h; | Under an argon atmosphere, Au(PPh3)Cl (474 mg, 0.96 mmol), <strong>[884494-34-2]5-fluoro-2-pyridylethyne</strong> (174 mg, 1.44 mmol) and ethanol (19 ml) were added to a 20 ml Schlenk tube, and then sodium ethoxide (395 mul, 1.01 mmol: 2.55 mol/L (liter) in ethanol solution) was added dropwise thereto and the mixture was stirred at room temperature for 17 hours. After completion of the reaction, the resulting white precipitate was filtered and successively washed with ethanol (12 mlxthree times), water (12 mlxthree times) and ethanol (6 mlxthree times), followed by drying under vacuum to give 0.48 g of the desired compound as a yellow powder (yield: 86%). 1H-NMR (400 MHz, CDCl3) delta: 8.37 (d, 1H), 7.23-7.59 (m, 18H), (FAB-MS) (M/Z): 580 (M+H)+ Luminescence analysis: (CHCl3, 77K, Ex250nm) lambda (nm): 418, 446, 457 Elemental analysis: Found C: 51.51, H: 3.02, N: 2.47 Theoretical C: 51.83, H: 3.13, N: 2.42 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium ethanolate; In ethanol; at 20℃; for 17h; | Under an argon atmosphere, Au(PPh3)Cl (488 mg, 0.99 mmol), <strong>[853909-08-7]6-fluoro-3-pyridylethyne</strong> (179 mg, 1.48 mmol) and ethanol (20 ml) were added to a 20 ml Schlenk tube, and then sodium ethoxide (408 mul, 1.04 mmol: 2.55 mol/L (liter) in ethanol solution) was added dropwise thereto and the mixture was stirred at room temperature for 17 hours. After completion of the reaction, the resulting white precipitate was filtered and successively washed with ethanol (12 ml .x. three times), water (12 ml .x. three times) and ethanol (6 ml .x. three times), followed by drying under vacuum to give 0.42 g of the desired compound as a yellow powder (yield: 73percent). 1H-NMR (400 MHz, CDCl3) delta: 8.35 (s, 1H), 7.81-7.87 (m, 1H), 6.80-6.84 (m, 1H) (FAB-MS) (M/Z): 580 (M+H)+ Luminescence analysis: (CHCl3, 77K, Ex250nm) lambda (nm): 413, 433, 442, 452 Elemental analysis: Found C: 51.76, H: 3.05, N: 2.51 Theoretical C: 51.83, H: 3.13, N: 2.42 |