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.
* 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.
1-(6,6a-dihydro-5H-benzo[a]carbazol-11(11aH)-yl)ethanone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
10%
With palladium diacetate; silver carbonate; In acetone; at 70℃; for 4h;
General procedure: To a stirred solution of 6 (0.5 mmol), tosyl-2-iodoaniline 5a or 5e (0.75 mmol), mesyl-2-iodo-aniline 5b (0.75 mmol), Cbz-2-iodoaniline 5c (0.75 mmol) or Acetyl-2iodoaniline 5d (0.75 mmol), in acetone (5 mL), silver-carbonate (1.5 mmol) and Pd(OAc)2 (0.005 mmol) were added. The reaction mixture was refluxed for 4 h and filtered in celite with ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude product was washed in n-hexane and purified by flash chromatography on silica.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
