Facile synthesis of TMS-protected trifluoromethylated alcohols using trifluoromethyltrimethylsilane (TMSCF3) and various nucleophilic catalysts in DMF.
Organofluorine compounds are becoming increasingly important in different fields, such as material science, agro chemistry, and the pharmaceutical industry. Nucleophilic trifluoromethylation is one of the widely used methods to incorporate a trifluoromethyl moiety into organic molecules. We have carried out extensive studies to develop varieties of easily accessible nucleophilic catalysts to promote such reactions. TMS-protected trifluoromethylated alcohols were prepared from both aldehydes and ketones in excellent yields using catalytic amount of amine N-oxide. Carbonate and phosphate salts also showed efficient catalytic activity toward this reaction. These reactions were highly solvent dependent, and DMF was found to be the most suitable one among the various solvents studied. All these reactions proceeded under very mild conditions, giving clean products and avoiding the use of any fluoride initiators or expensive catalysts, and extremely water-free conditions. The mechanism for the reaction is discussed in detail. DFT calculations were performed on the possible reaction intermediates using the Gaussian 03 program at B3LYP/6-311+G* level to support the proposed mechanism.
Prakash
G K Surya
GK
Donald P. and Katherine B. Loker Hydrocarbon Research Institute, and Department of Chemistry, University of Southern California, 837 Bloom Walk, Los Angeles, CA 90089-1661, USA. gprakash@usc.edu
Panja
Chiradeep
C
Vaghoo
Habiba
H
Surampudi
Vijayalakshmi
V
Kultyshev
Roman
R
Mandal
Mihirbaran
M
Rasul
Golam
G
Mathew
Thomas
T
Olah
George A
GA
D000438:Alcohols / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D004126:Dimethylformamide / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D012821:Silanes / Q000737:chemistry*
D000438:Alcohols; D006845:Hydrocarbons, Fluorinated; D012821:Silanes; D004126:Dimethylformamide; D010100:Oxygen