The First Regioselective Metalation and Functionalization of Unprotected 4-Halobenzoic Acids

Abstract

[reaction: see text] By treatment with s-BuLi, s-BuLi/TMEDA, or t-BuLi at approximately -78 degrees C, 4-fluoro- and 4-chlorobenzoic acids (1a,b) are metalated preferentially in the position adjacent to the carboxylate. A complete reversal in regioselectivity is observed for 1a when treated with LTMP; a sequential process involving a rapid intraaggregate lithiation through a quasi dianion complex "QUADAC" is postulated to explain the unusual reactivity of Me(2)S(2) and I(2).

The Expedient and Regioselective Metalation of Unprotected Biphenyl‐2‐, ‐3‐, and ‐4‐carboxylic Acids

“…[8] The metalation of 4-fluoro-and 4-chlorobenzoic acids 2a, 2b results in exclusive reaction ortho to the carboxylate with sBuLi, sBuLi/TMEDA, or tBuLi, but LTMP selectively metalates the C3-positions. [9] These results corroborate the concept of the achievement of regiocontrol in hy-Metalation of Unprotected Biphenyl-2-, -3-, and -4-carboxylic Acids FULL PAPER drogen/metal exchange processes through mechanism-based matching of substituents and reagents. [10] Here we report on the reactivity of biphenyl-2-, -3-, and -4-carboxylic acids 3-5 towards sterically hindered lithium amides, alkyllithiums, and LICKOR.…”

The directing group wins over acidity: kinetically controlled regioselective lithiation for functionalization of 2-(2,4-dihalophenyl)-1,3-dithiane derivatives

“…2, 133.5, 132.5, 129.4, 127.0 (d, J = 8.0 Hz), 115.1 (d, J = 21.0 Hz), 72.1, 70.5, 37.4, 27.8, 22.4, 14.0;IR (KBr): ν 3545, 2937, 1610, 1512, 1440, 1221, 1054 7, 138.1, 136.9, 134.8, 133.4, 133.2, 129.6, 126.6, 113.6, 72.6, 55.2, 47.6, 32.2, 24.9;IR (neat): ν 3457, 2955IR (neat): ν 3457, , 2903IR (neat): ν 3457, , 2830IR (neat): ν 3457, , 1609IR (neat): ν 3457, , 1583IR (neat): ν 3457, , 1511IR (neat): ν 3457, , 1443IR (neat): ν 3457, , 1247IR (neat): ν 3457, , 1180IR (neat): ν 3457, , 1081IR (neat): ν 3457, , 1029 2, 138.2, 138.0, 136.9, 134.9, 133.5, 129.7, 129.6, 128.2, 128.0, 126.0, 122.3, 72.8, 47.6, 32.2, 24.9, 21.5;IR (neat): ν 3430, 2898IR (neat): ν 3430, , 1577IR (neat): ν 3430, , 1451IR (neat): ν 3430, , 1276IR (neat): ν 3430, , 1150IR (neat): ν 3430, , 1073IR (neat): ν 3430, , 1035 8, 146.7, 138.0, 137.0, 135.2, 134.8, 133.4, 129.8, 129.7, 118.6, 108.0, 106.3, 101.0, 72.7, 47.6, 32.2, 24.9;IR (KBr): ν 3425, 2882, 1682, 1501, 1485, 1441, 1238, 1041 2, 138.1, 136.82, 136.80, 134.8, 133.4, 129.59, 129.55, 128.9, 125.2, 72.7, 47.6, 32.1, 24.9, 21.0;IR (neat): ν 3572, 3457, 2898IR (neat): ν 3572, 3457, , 1906IR (neat): ν 3572, 3457, , 1572IR (neat): ν 3572, 3457, , 1506IR (neat): ν 3572, 3457, , 1440IR (neat): ν 3572, 3457, , 1276IR (neat): ν 3572, 3457, , 1079 …”

“…1, 136.9, 134.9, 133.4, 129.7, 129.6, 128.2, 127.1, 125.2, 72.7, 47.6, 32.1, 24.9; IR (KBr): ν 3545, 3063, 2937, 1577, 1501, 1451, 1276, 1183, 1084, 700 cm −1 ; HRMS calcd for C 17 H 16 Cl 2 NaOS 2 (M + Na) +…”

Chemoselectivity of cobalt-catalysed carbonylation—A reliable platform for the synthesis of fluorinated benzoic acids

“…However, the description of the preparation of different fluorinated benzoic acids (except 4-fluorobenzoic acid) has not been published until 2007 [11]. Comparison of our preparative results [11] with the reported routes for the synthesis of these products [19][20][21][22] revealed that a universal method of synthesis of different fluorosubstituted benzoic acids from available raw materials with good yields has been elaborated for the first time. High selectivity of carbonylation of these substrates (95-100%) and excellent preparative yields (85-95%) can serve in favor of S RN 1 mechanism.…”