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Relay Propagation of Crowding: The Trifluoromethyl Group as Both an Emitter and Transmitter of Steric Pressure
Author(s) -
Schlosser Manfred,
Cottet Fabrice,
Heiss Christophe,
Lefebvre Olivier,
Marull Marc,
Masson Eric,
Scopelliti Rosario
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500728
Subject(s) - trifluoromethyl , chemistry , substituent , quinoline , steric effects , deprotonation , phenyl group , medicinal chemistry , methyl group , isopropyl , stereochemistry , organic chemistry , group (periodic table) , alkyl , halogen , ion
Whereas lithium 2,2,6,6‐tetramethylpiperidide (LITMP) abstracts a proton exclusively from the 4‐position of 3‐bromobenzotrifluoride, the same base attacks selectively the 2‐position when employed in the presence of N , N , N′ , N′′ , N′′ ‐pentamethyldiethylenetriamine and potassium tert ‐butoxide (“Faigl mix”). 1‐Bromo‐3,5‐bis(trifluoromethyl)benzene also undergoes metalation at the 2‐position but [2‐bromo‐4‐(trifluoromethyl)phenyl]silane does not react at all, evidently locked up by a C–SiR 3 /C–Br buttressing effect. 2‐Bromo‐4‐(trifluoromethyl)pyridine, aza‐analogous to the parent model arene 3‐bromobenzotrifluoride, and both the benzo‐aza‐analogous 2‐bromo‐4‐(trifluoromethyl)quinoline and its regioinverted isomer 4‐bromo‐2‐(trifluoromethyl)quinoline are again readily deprotonated at the Br‐ and CF 3 ‐flanked positions. However, the buttressing caused by the introduction of a methoxy group at the peri ‐(5‐)position impedes the deprotonation of either bromo(trifluoromethyl)quinoline. Compared with methoxy, a peri ‐methyl substituent (to be assimilated to an ortho‐tert ‐butyl substituent) exerts a smaller buttressing effect. Although 4‐bromo‐5,7‐ dimethoxy ‐4‐(trifluoromethyl)quinoline proves to be again totally inert towards bases, 4‐bromo‐5,7‐ dimethyl ‐4‐(trifluoromethyl)quinoline can be lithiated at the 3‐position. Obviously, methoxy is more powerful as an emitter of steric pressure than methyl is and bromine is superior to trifluoromethyl as a transmitter of steric pressure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)