![]() How can I achieve complete ketimine formation for more challenging substrates? Yes! Acetonitrile, benzene, toluene, and 1,2-dichloroethane (DCE) all afforded the ketimine within the indicated time. Ketimine FormationĬan other solvents be used in case of solubility issues during the ketimine formation? However, most imines decompose on silica gel. Slow decomposition can be observed in CDCl 3 if recording of NMR signals takes a prolonged amount of time (more than 1 hour).ĭepending on the aldehydes used, few imines can withstand purification using flash column chromatography. How stable are the resulting imines and can they be purified using flash column chromatography?Īs a general rule, imines are stable at room temperature for several hours and no special precautions are needed in the isolation step. ![]() In case of the catalytic cyclization protocol, the basic primary amine of unreacted SnAP reagents tends to lower the catalyst efficiency resulting in incomplete conversion. No, if Cu(OTf) 2 is used in a stoichiometric amount. Yes! Acetonitrile, benzene, toluene, and 1,2-dichloroethane (DCE) all afforded the imine within the indicated time.ĭoes leftover aldehyde harm the cyclization if a slight excess was used in the imine formation?ĭoes leftover SnAP reagent harm the cyclization if a slight excess was used in the imine formation? Purification FAQ here!įrequently Asked Questions Imine FormationĬan other solvents be used in case of solubility issues during the imine formation? If desired, further purification could be carried out by salt formation of the unprotected N-heterocycles to remove any trace of tin impurities. The polarity difference of the product heterocycles and tin byproducts allows for simple flash column chromatography to remove tin byproducts. Cyclization FAQ here! Step 3: Purification Purification by flash column chromatography affords the corresponding unprotected heterocyclic compounds. The combined organic layers are washed with H 2O and brine, dried over anhydrous Na 2SO 4, filtered, and concentrated. The layers are separated and the aqueous layer is extracted with CH 2Cl 2. The reaction mixture is diluted with CH 2Cl 2, treated with a solution of 12% aq NH 4OH and brine (1:1), and stirred vigorously for 15 min at rt. A solution of the imine or ketimine (0.50 mmol, 1.00 equiv) in the appropriate amount of CH 2Cl 2/HFIP is added in one portion and the resulting mixture is stirred at rt for 16 h. 2,6-Lutidine (0.50 mmol, 1.00 equiv) is added and the resulting bluish suspension is stirred at rt for 1 h to afford a dark green suspension. Ketimine Formation FAQ here! Step 2: CyclizationĪnhydrous Cu(OTf) 2 – dried for 2 h at 110☌ at 0.1 mbar – (0.50 mmol, 1.00 equiv) is suspended in the appropriate amount of HFIP. The filtrate was concentrated under reduced pressure to afford the pure ketimine. The reaction mixture was stirred at rt for 12 h and filtered through a short layer of Celite (CH 2Cl 2 rinse) to remove the molecular sieves. Ketimine Formation: To a solution of the SnAP reagent (0.50 mmol, 1.00 equiv) in CH 2Cl 2 (0.5 mL) at rt was added the corresponding ketone (0.50 mmol, 1.00 equiv) and MS 4A powder (ca. The filtrate was concentrated under reduced pressure to afford the pure imine. The reaction mixture was stirred at rt for 2–6 h and filtered through a short layer of Celite (CH 2 Cl 2 rinse) to remove the molecular sieves. Imine Formation: To a solution of the SnAP reagent (0.50 mmol, 1.00 equiv) in CH 2 Cl 2 (2.5 mL) at rt was added the corresponding aldehyde (0.50 mmol, 1.00 equiv) and MS 4A powder (ca. No special precautions were necessary for reaction set-up and all experiments were performed using identical reaction conditions without substrate-specific optimization.
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