Ipso-fluoro displacement

In a closely related study, Tung and Sun discussed the microwave-assisted liquid-phase synthesis of chiral quinoxalines [80], Various L-a-amino acid methyl ester hydrochlorides were coupled to MeOPEG-bound ortho-fluoronitrobenzene by the aforementioned ipso-fluoro displacement method. Reduction under microwave irradiation resulted in spontaneous synchronous intramolecular cyclization to the corresponding l,2,3,4-tetrahydroquinoxalin-2-ones (Scheme 7.71). Retention of the chiral moiety could not be monitored during the reaction, but after release of the desired products it was found that about 10% of the product had undergone racemization. 

IL-anchored orffeo-phenylenediamine 97 was used as a common scaffold to construct skeletal diversity of novel heterocyclic molecules using various acids, isothiocyanate, and cyanogen bromide (Scheme 12). IL-supported 97 condensation with 3-nitrobenzoic acids followed by cyclization gave benzimidazole heterocycles 100. The ipso-fluoro displacement by primary amine and subsequent nitro reduction resulted benzimidazole-linked o-phenylenediamine 101. IL-grafted 101 was selected as a common scaffold to the synthesis of 2-alkyl-substituted l zs-benzimidazole 102, and pyrrole[l,2-fl]benzimidazolones 103 using various keto acids in one step (Scheme 12) [43]. IL-supported pyrrole[l,2-a]benzimidazolones 103 were treated with Lawesson s reagents to afford thiopyr-ido-benzimidazolone 106. 

Schemesl2 and 13) [43-53]. Privileged structures of IL-immobilized diamines 97 and 99 were synthesized from 4-fluoro-3-nitrobenzoic acid and 4-(bromomethyl)-3-nitrobenzoic acid, respectively over three steps (Scheme 14). The ionic liquid 3-hydroxyethyl (l-methylinidazolium)-tetrafluoroborate ([hydemim][BF4]) 1 was selected as appropriate IL support in all multistep transformations. Benzoic acid 94 coupled with IL1 through esterification followed by ipso-fluoro and bromo displacement by primary amines and subsequent nitro reduction afforded ort/fo-phenylenediamines 97 and 99. 

The chemistry involved in nucleophilic aromatic substitution is well reflected in the reactions of a variety of nucleophiles with methyl penta-fluorophenyl ether (Ingemann et al 1982a). For most of the nucleophiles such as alkoxide, thiolate, enolate and (un)substituted allyl anions, the dominant reaction channel is the attack upon the fluoro-substituted carbon atoms, as is the case for OH-. The latter ion reacts approximately 75% by attack upon the fluoro-substituted carbon atoms and the remaining 25% by Sn2 (20%) and ipso (5%) substitution as summarized in (41). In the attack upon the fluorinated carbon atoms, the interesting observation is made that a F- ion is displaced via an anionic o-complex to form a F- ion/molecule complex, which is not observed to dissociate into F- as a free ionic product. 

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