Buttressing Effects Rerouting the Deprotonation and Functionalization of 1,3‐Dichloro‐ and 1,3‐Dibromobenzene

Abstract

A systematic comparison between 1,3‐difluorobenzene, 1,3‐dichlorobenzene, and 1,3‐dibromobenzene did not reveal major differences in their behavior towards strong bases such as lithium diisopropylamide or lithium 2,2,6,6‐tetramethylpiperidide. Thus, all 2,6‐dihalobenzoic acids 1 are directly accessible by consecutive treatment with a suitable base and dry ice. In contrast, (2,6‐dichlorophenyl)‐ and (2,6‐bromophenyl)triethylsilane (2a and 2b) were found to undergo deprotonation at the 5‐position (affording acids 3 and, after deprotection, 4), whereas the 1,3‐difluoro analog is known to react at the 4‐position. The 2,4‐dihalobenzoic acids 7 were selectively prepared from either the silanes 2 (by bromination at the 4‐position, metalation and carboxylation of the neighboring position, followed by desilylation and debromination) or the 1,3‐dihalo‐2‐iodobenzenes 8 (by base‐promoted migration of iodine to the 4‐position followed by iodine/magnesium permutation and subsequent carboxylation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Trifluoromethyl‐Substituted Phenylsilanes: The Regiochemical Course of Their Metalation Dictated by Buttressing Effects

“…[6,7] The proneness to meta attack should manifest itself more pronouncedly if a buttressing interaction [1,8,9] discriminates against ortho-metalation. In fact, triethyl[(2-trifluoromethyl)phenyl]silane (1) was found to undergo hydrogen/metal permutation ("metalation") exclusively at the CF 3 -remote 4-position and not at all at the CF 3 -adjacent 3-position.…”

Substituent effects on the relative rates and free energies of ortho-lithiation reactions: families of fluorobenzenes as the substrates

“…In some cases (e.g. with X = SiMe 3 ), buttressing effects [34][35][36][37][38][39][40][41] (steric effects exerted by the X group through the fluoro group) 42 may compromise the reactivity of the 1,2-isomers 2. More importantly, the acidifying effect of substituents at meta positions is no longer the same as at ortho positions.…”

Long-range Effect of Bromine in the Deprotonative Metalation of Aromatic Compounds

“…[23] In this case, metalation no longer takes place at the halogen-adjacent position, but solely at the halogen-remote meta position owing to the long-range acidifying effect of the heavy halogen (Scheme 9). [24] Besides chlorotrimethylsilane, it is possible to intercept arylmetal species generated by deprotonative metalation through using LiDA in the presence of chlorotrimethylsilane as in situ trap (indeed, Li-DA reacts with the aromatic halide more rapidly than it does with chlorotrimethylsilane). Nevertheless, a second deprotolithiation-silylation cannot be avoided, leading to mixtures containing both 1,2-dibromo-3-(trimethylsilyl)benzene (12c) and 2,3-dibromo-1,4-bis(trimethylsilyl) benzene (12c').…”

“…Thus, aromatic compounds bearing sensitive groups such as 18a were functionalized through a deprotometalation step using Mg(TMP) 2 ·2LiCl in the presence of ZnCl 2 (Scheme 10). [24] Long-range Effect of Bromine in the Deprotometalation of Aromatic Heterocycles…”