Cyclohexadienyl anion substitution

A nitro group is a strongly activating substituent in nucleophilic aromatic substitution where it stabilizes the key cyclohexadienyl anion intermediate... 

Cycloalkene (Section 5 1) A cyclic hydrocarbon characterized by a double bond between two of the nng carbons Cycloalkyne (Section 9 4) A cyclic hydrocarbon characterized by a tnple bond between two of the nng carbons Cyclohexadienyl anion (Section 23 6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism It is represented by the general structure shown where Y is the nucleophile and X is the leaving group... 

Cyclohexadienyl anion (Section 23.6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism. It is represented by the general structure shown, where Y is the nucleophile and X is the leaving group. 

Diethyl sodiomalonate is an example of type (i). Reaction with [(fluorobenzene)Cr(CO)3] proceeds to completion after 20 h at 50 C in HMPA to give the diethyl phenylmalonate complex in over 95% yield. Monitoring the reaction by NMR gave no evidence for an intermediate (e.g. the cyclohexadienyl anion complex) interruption of the reaction by addition of iodine at less than 20 h gave significant amounts of unreacted fluorobenzene. A satisfactory picture is the simple one, that the anion adds reversibly and unfavorably (k < k-i, as in Scheme 3), slowly finding itself at the ipso position then irreversible loss of fluoride gives the substitution product.5152... 

The processes depend on the formation of the cyclohexadienyl anion intermediates in a favorable equilibrium (carbon nucleophiles from carbon acids with pKt > 22 or so), protonation (which can occur at low temperature with even weak acids, such as acetic acid) and hydrogen shifts in the proposed diene-chromium intermediates (25) and (26). Hydrogen shifts lead to an isomer (26), which allows elimination of HX and regeneration of an arene-chromium complex (27), now with the carbanion unit indirectly substituted for X (Scheme 9). 

Intermolecular Nucleophilic Substitution with Heteroatom Nucleophiles. A patent issued in 1965 claims substitution for fluoride on fluorobenzene-Cr(CO)3 in dimethyl sulfoxide (DMSO) by a long list of nucleophiles including alkoxides (from simple alcohols, cholesterol, ethylene glycol, pinacol, and dihydroxyacetone), carboxylates, amines, and carbanions (from triphenyhnethane, indene, cyclohexanone, acetone, cyclopentadiene, phenylacetylene, acetic acid, and propiolic acid). In the reaction of methoxide with halobenzene-Cr(CO)3, the fluorobenzene complex is ca. 2000 times more reactive than the chlorobenzene complex. The difference is taken as evidence for a rate-limiting attack on the arene ligand followed by fast loss of halide the concentration of the cyclohexadienyl anion complex does not build up. In the reaction of fluorobenzene-Cr(CO)3 with amine nucleophiles, the coordinated aniline product appears rapidly at 25 °C, and a carefiil mechanistic study suggests that the loss of halide is now rate limiting. 

Lithio isobutyronitrile is an example of anion type (b). The initial addition to chlorobenzene Cr(CO)3 is over within minutes at -78 °C, but the substitution product does not appear until the mixture is warmed to 25 °C. Quenching with iodine after a short reaction time leads to a mixture of phenyl-isobutyronitrile and o- and (m-chlorophenyl)isobutyronitrile. This appears to be a case of fast addition ortho and meta to the chloride to give cyclohexadienyl anionic complexes, followed by slow rearrangement to the ipso intermediate. Quenching with iodine before equilibration is complete leads to oxidation of the intermediates and formal substitution for hydrogen. 

The efficient trapping of the cyclohexadienyl anionic intermediates with protons raises the possibility of qnenching with carbon electrophiles. The process is not as general as the proton quench. However, when the nucleophile adds essentially irreversibly, quenching with a limited set of carbon electrophiles is successful. For example, addition of 2-lithio-l,3-dithiane to benzene-Cr(CO)2T, followed by addition of ethyl iodide and then oxidation or addition of a donor ligand (CO, PhsP), produces a cyclohexa-l,3-diene substituted by both acetyl (Me + CO) and the nucleophile (Scheme 47).134,209 insertion of CO occurs, without... 

Once it is recognized that cyclohexadienyl anionic complexes of chromium (41) can be generated by addition of sufficiently reactive nucleophiles and that simple oxidizing techniques convert the anionic intermediates to free substituted arenes, a general substitution process becomes available which does not depend on a specific leaving group on the arene [2]. The process is general for carban-ions derived from carbon acids with pK >22 or so only one example of a heteroatom nucleophile is reported [102]. 

Nucleophilic addition to the arylchromium complex occurs from the face opposite the bulky chromium atom and gives an intermediate rf-cyclohexadienyl anion complex, such as 176 (1.177). If the nucleophile attacks at the same carbon atom as a halide substituent ipso position), then subsequent loss of the halide leads to an overall nucleophilic substitution. This type of reaction is most effective with fairly soft nucleophiles pK < 20), in which nucleophilic attack is thought to be reversible. 

When an aromatic ring is substituted with an electron-withdrawing group such as a nitro group (X=N02), nucleophilic aromatic substitution can occur by a process that involves the formation of a cyclohexadienyl anion. 

These results led Semmelhack and his colleagues to study the addition of carbanions to benzenetricarbonylchromium itself. Carbanions derived from species with pK 25 in tetrahydrofuran form cyclohexadienyl anions which are stable below 0°C in the absence of air. Oxidation with iodine affords substituted benzenes. The sequence... 

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