Organometallic Control over the Regiospecificity of Functionalization Reactions: 1,2,3‐Trifluorobenzene and Bromo Derivatives thereof as Substrates

Abstract

In a case study, 1,2,3-trifluorobenzene was functionalized at each of the two vacant positions (producing the benzoic acids 1 and 2) and, in addition, bromine was introduced into all available positions (producing the benzoic acids 3−5). The required regioflexibility was achieved by applying novel orAt first glance, 1,2,3-trifluorobenzene hardly qualifies as a good example for demonstrating the merits of the organometallic approach to the creation of molecular diversity. [1] Having just two regiochemically distinct sites unoccupied, any deprotonation/functionalization sequence can give rise to not more than two isomers. To make our exercise in regioflexibility more demanding, we have therefore allowed for the presence of an additional substituent by targeting both the two trifluorobenzoic acids 1 and 2 and also the three bromo derivatives 3Ϫ5. The chart shown below summarizes the transformations involving the bromo-, iodo-, or triethylsilyl-substituted trifluorobenzenes 6Ϫ14. Details will be specified in the subsequent sections.The ortho-lithiation of 1,2,3-trifluorobenzene with secbutyllithium in tetrahydrofuran at Ϫ75°C has already been reported.[2] Subsequent carboxylation and neutralization afforded 2,3,4-trifluorobenzoic acid (1) in 94% yield.In contrast, a multi-step procedure was required to prepare 3,4,5-trifluorobenzoic acid (2). Treatment of the metalated species with elemental bromine gave 1-bromo-2,3,4-trifluorobenzene (7; 95%), which was converted into (5-bromo-2,3,4-trifluorophenyl)triethylsilane (8; 92%) upon subsequent reaction with lithium diisopropylamide (LIDA) and chlorotriethylsilane. Heating silane 8 with bromine for [a] 36 h in refluxing tetrachloromethane produced 1,5-dibromo-2,3,4-trifluorobenzene (9; 93%). The dibromo compound 9 (95%) was also formed when the bis(silane) 6, resulting in 91% yield from the twofold repetitive reaction

Fluoronaphthalene Building Blocks via Arynes: A Solution to the Problem of Positional Selectivity

“…The next step should be an attempt to promote cycloadditions between 3-fluoro-6-trimethylsilyl-1,2-didehydrobenzene and 2-(trimethylsilyl) furans that carry a second substituent, for example, bromine, methoxymethoxy, or methyl, at the 5-position. The resulting 1,4-epoxy-1,4-dihydronaphthalenes could then be deoxygenated to the corresponding naphthalenes with zinc powder [5] or low-valent titanium, [3] and the two trimethylsilyl groups located in different environments could possibly be induced to undergo a consecutive displacement by protodesilylation, [16,17] bromodesilylation, [16,18] or iododesilylation. [16,19] Alternatively, the 1,4-epoxy-1,4-dihydronaphthalenes could be converted into phenols by acid catalysis, again regioselectively.…”

meta‐ Rather than ortho‐Directed Metalations: Buttressing Effects Prejudicing the Proton Abstraction from (2,6‐Dihalophenyl)silanes

“…When the aryne was set free in the presence of a threefold excess of tert-butyllithium, nucleophilic addition of the latter occurred. Upon neutralization, (5-tert-butyl-2-chlorophenyl)trimethylsilane (11) and, upon protodesilylation, 1-tert-butyl-4-chlorobenzene (12) were both obtained in 73 % yield, respectively. The latter product was separately prepared from the commercial 1-bromo-4-tert-butylbenzene by consecutive halogen/metal permutation and chlorination with 1,1,2-trichloro-1,2,2-trifluoroethane.…”

The Kinetic Acidity of Oligofluorobenzenes Correlated with Their Gas Phase Deprotonation Energies

“…[8] Experimental Section Generalities: Abbreviations and laboratory routines have been explained in previous publications from this laboratory. [9][10][11][12] The stationary phases of the gas chromatography columns used in the present work are encoded as BGB-2.5 (= 2.5 % of diphenylpolysiloxane and 97.5 % of dimethylpolysiloxane), Bentone (= 50 % of dimethyloctadecylammonium bentonite and 50 % of didecylphthalate), DB-1701 (= 14 % of cyanopropylphenylpolysiloxane + 86 % of dimethylpolysiloxane); DB-FFAP (= polyethylene glycol) and DB-WAX (= acid modified polyethylene glycol).…”