Fluorophenols and (trifluoromethyl)phenols as substrates of site-selective metalation reactions: to protect or not to protect
O-Methoxymethyl (MOM) protected fluorophenols can be cleanly metalated and subsequently be submitted to site-selective electrophilic substitution. The 2- and 4-isomers exhibit ambivalent reactivity: deprotonation occurs at the position adjacent to the O when butyllithium is employed whereas the position adjacent to the F is attacked by the superbasic mixt. of butyllithium and K tert-butoxide (LIC-KOR). The MOM-protected (trifluoromethyl)phenols react exclusively at O-neighboring positions. The meta isomer provides another example of optional site selectivity, undergoing H/metal exchange at the 2-position with the LIC-KOR reagent and at the 6-position with sec-butyllithium. Unprotected (trifluoromethyl)phenols can also be ortho-metalated after O-deprotonation, although the products are formed in only moderate yields. [on SciFinder (R)]
Cite this item
Marzi, E., Mongin, F., Spitaleri, A., & Schlosser, M. (2001). Fluorophenols and (trifluoromethyl)phenols as substrates of site-selective metalation reactions: to protect or not to protect. European Journal of Organic Chemistry, (15), 2911–2915. https://doi.org/10.1002/1099-0690(200108)2001:15<2911::AID-EJOC2911>3.0.CO;2-W
Click Copy to copy the citation, or select the text manually.
2001
15
2911
2915
CAN 135:318295 25-17 Benzene, Its Derivatives, and Condensed Benzenoid Compounds Institut de Chimie organique de l'Universite,Lausanne,Switz. Journal 1434-193X written in English. 117570-31-7P (1-Fluoro-2-(methoxymethoxy)benzene); 126940-10-1P (1-Fluoro-3-(methoxymethoxy)benzene); 141362-06-3P (1-Fluoro-4-(methoxymethoxy)benzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and reactant as protected in prepn. of fluorohydroxybenzoic acid); 174265-24-8P (1-(Methoxymethoxy)-4-trifluoromethylbenzene); 334018-79-0P (1-(Methoxymethoxy)-3-trifluoromethylbenzene); 336628-65-0P (1-(Methoxymethoxy)-2-trifluoromethylbenzene) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and reactant as protected in prepn. of trifluoromethylhydroxybenzoic acid); 368422-22-4P; 368422-23-5P; 368422-24-6P; 368422-25-7P; 368422-26-8P; 368422-27-9P; 368422-28-0P; 368422-29-1P; 464895-12-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. from protected-metalated fluoromethylphenol); 328-90-5P (2-Hydroxy-4-(trifluoromethyl)benzoic acid); 51446-30-1P (2-Fluoro-5-hydroxybenzoic acid); 79427-88-6P (2-Hydroxy-5-(trifluoromethyl)benzoic acid); 91658-92-3P (2-Fluoro-3-hydroxybenzoic acid); 144433-66-9P (2-Hydroxy-6-(trifluoromethyl)benzoic acid); 251300-32-0P (2-Hydroxy-3-(trifluoromethyl)benzoic acid); 368422-30-4P; 368422-31-5P; 368422-32-6P; 368422-33-7P; 368422-34-8P; 368422-35-9P; 368422-36-0P; 368422-37-1P; 368422-38-2P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. from protected-metalated fluoromethylphenol); 98-17-9 (3-Trifluoromethylphenol); 107-30-2 (Chloromethyl methyl ether); 367-12-4 (2-Fluorophenol); 371-41-5 (4-Fluorophenol); 372-20-3 (3-Fluorophenol); 402-45-9 (4-Trifluoromethylphenol); 444-30-4 (2-Trifluoromethylphenol) Role: RCT (Reactant), RACT (Reactant or reagent) (reactant for prepn. of fluorohydroxybenzoic acids and hydroxy(trifluoromethyl)benzoic acids via protected-metalated fluoromethylphenol); 341-27-5P (3-Fluoro-2-hydroxybenzoic acid); 345-16-4P (5-Fluoro-2-hydroxybenzoic acid); 67531-86-6P (2-Fluoro-6-hydroxybenzoic acid) Role: SPN (Synthetic preparation), PREP (Preparation) (reactant for prepn. of fluorohydroxybenzoic acids and hydroxy(trifluoromethyl)benzoic acids via protected-metalated fluoromethylphenol)
REVIEWED
EPFL