Vicarious reaction

In recent years there has been a proliferation of new reactions and reagents that have been so useful in organic synthesis that often people refer to them by name. Many of these are stereoselective or regioselecth/e methods. While the expert may know exactly what the Makosza vicarious nucleophilic substitution, or the Meyers asymmetric synthesis refers to, many students as well as researchers would appreciate guidance regarding such "Name Reactions". 

Replacement of an aromatic fluorine atom by a carbon nucleophile is facihtated by the presence of electron-withdrawmg groups [82] (equation 44) Replacement of an activated aryl hydrogen can occur in preference to a nonactivated aryl fluorine [Si] (equation 45) in reactions known as vicarious subsututions. 

In contrast, reaction of 82 with NaCN in DMF-H2O at reflux results in the formation of 7-cyano-6-nitroindole (201, 15%) and 83 (4%) as isolable products together with tar matter, and, to our surprise, 2- and/or 3-cyano-6-nitroindoles are not detected at all. When the reaction is carried out in DMSO at 150°C, only demethoxylation occurred to give 83 (62%). On the other hand, utilizing KOt-Bu and p-chlorophenoxyacetonitrile (25), the vicarious substitution reaction (87ACR282) of 82 proceeds smoothly to give a 7-cyanomethylated indole (202, 67%) (2001H1151). 

The reaction of 3-methoxy-1,2,4-triazine 1-oxide 20 with the carbanion generated from chloromethyl phenyl sulfone proceeds as the vicarious nucleophilic substitution (VNS) of hydrogen (Scheme 1, path B) via addition of the carbanion at position 5 of the heterocycle. Following base-induced elimination of HCl and protonation, 3-methoxy-5-phenylsulfonyl-1,2,4-triazine 4-oxides 65 result (88LA627). 

A similar reaction is probably involved in the reaction of 4-nitrophthalodi-nitrile (27) with dimedone (28), which provided under milder condition compound 29 and at a higher temperature tricyclic compound 30 (87ZOR2629). Similarly as in the vicarious nucleophilic reactions, intermediate 29 is formed by nucleophilic displacement of the ort/io-hydrogen atom in 27 (Scheme 3). 

Reaction of halo sulfonic acid esters with boranes 10-125 Alcoholysis of sulfonic acid derivatives 13-15 Vicarious substitution of aryl nitro compounds... 

The carbanion of 2,3-dimethylthiazolidine-4-one reacted with nitroarenes to give either a ting opened product (50) via a VNS (vicarious nucleophilic substitution) reaction or a product resulting from oxidative nucleophilic substitution of hydrogen (51). Ring opening VNS reactions with 5-membered 5-heterocycles are limited to those heterocycles which show some conformational flexibility <96TL983>. 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

The vicarious nucleophilic substimtion of carbo- and hetero-cyclic nitroarene hydrogen by a hydroxyl group, on reaction with silylhydroperoxide anions, has been shown to proceed via nucleophilic addition of ROO followed by base induced elimination of ROH by an ii2-type mechanism the required orientation of the hydroxylation can be controlled by the conditions selected. ... 

A number of heterogeneous systems have been developed for oxidation reactions using H2O2 as oxygen source . In 1981, Taramasso, Notari and collaborators at Enichem opened new perspectives in this field with the discovery of the Ti-silicalite (TS-1) ° , a new synthetic zeolite of the ZSM family. In the TS-1 zeolite, titanium atoms are located in vicariant positions in the place of Si atoms in the crystalline framework . The remarkable reactivity of TS-1 is likely ascribable to the site-isolation of tetrahedral Ti(IV) in a hydrophobic environment. TS-1 has proved to be an efficient catalyst for the epoxidation of unfunctionalized short-chain olefins, especially terminal ones (equation 28). In addition, polyunsaturated compounds are mainly converted into the mono epoxides (equation 29). 

When the attacking atom of the nucleophile carries a leaving group, replacement of hydrogen can take place via the VNS (vicarious nucleophilic substitution) reaction,15 as shown in Scheme 3.16 The key feature of this reaction is the rate-limiting base-induced 3-elimination from the cr-adduct. 

Vicarious nucleophilic substitution reactions of azolopyridazines have been found to be controlled by methyl substituents.35 On treatment with bromomethyl phenyl sulfone in DMSO-r-BuOK, azolopyridazines yield mainly typical reaction products, whereas 7-methylazolopyridazines under the same conditions undergo annulation. These competitive reactions illustrate the role of charge distribution and steric hindrance for the course of the nucleophilic substitution. 

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