Relay propagation of crowding: the trifluoromethyl group as both an emitter and transmitter of steric pressure

Whereas lithium 2,2,6,6-tetramethylpiperidide (LITMP) abstrs. 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-SiR3/C-Br buttressing effect. 2-Bromo-4-(trifluoromethyl)pyridine, aza-analogous to the parent model arene 3-bromobenzotrifluoride, and both the benzo-azaanalogous 2-bromo-4-(trifluoromethyl)quinoline and its regioinverted isomer 4-bromo-2-(trifluoromethyl)quinoline are again readily deprotonated at the Br- and CF3-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-Me substituent (to be assimilated to an ortho-tert-Bu 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 Me is and bromine is superior to trifluoromethyl as a transmitter of steric pressure. [on SciFinder (R)]