Nucleophilic substitution 3 + 2 cyclizations

Nucleophilic substitution/cyclization strategy to tetrahydrofurans by Langer... 

Scheme 70 Nucleophilic substitution/cyclization strategy to tetrahydrofurans by Langer et al. [76]...

Scheme 13 Mechanistic considerations for nucleophilic substitution cyclizations...

Arylamino-2-chloroprop-2- enoic esters (72) obtained from 2-chloroaceto acetic ester (71) and arylamines, react with thiourea to yidd substituted 2-aminothiazoles (73), probably by initial nucleophilic substitution of the chloro atom of 72, followed by cyclization with loss of aniline (Scheme 33) (729). 

Intramolecular nucleophilic displacement of the bromo group by an azine-nitrogen occurs in the cyclization of A-2-quinaldyl-2-bromo-pyridinium bromide (248) to give the naphthoimidazopyridinium ring system. The reaction of 2-bromopyridine and pyridine 1-oxide yields l-(2-pyridoxy)pyridinium bromide (249) which readily undergoes an intramolecular nucleophilic substitution in which departure of hydrogen as a proton presumably facilitates the formation of 250 by loss of the JV-oxypyridyl moiety. 

The cyclization pathway proposed (81UK1252) involves nucleophilic substitution of the hetero group (XR) by the formamide amino group to form either enyne formamide 157 or imine 158. 

Highly electron-deficient 1,3,6-trinitrobenzene (145) treated with phenyl acet-amidines 146 in ethanol provided low yields of a dinitroindole derivatives, probably 4,6-dinitroindoles 148 (77JOC435). Formation of indole derivatives 148 can be explained by nucleophilic substitution of the activated aromatic hydrogen leading to intermediates 147, which then cyclized to the final products 148 (Scheme 22). 

Pyridino-oxazoles 198 were obtained in an analogous way starting from o-bromoaminopyridine 196, which was first acylated and then cyclized imder microwave irradiation at 165 °C in DMA via an aromatic nucleophilic substitution (Scheme 71) [126]. 

In the case of aromatic amines there is an initial nucleophilic substitution catalyzed by the silanol groups of the silica gel layer to yield arylaminobenzoquinone derivatives, that undergoe oxidative cyclization to the corresponding dioxazines [1]. 

Nucleophilic Substitutions and Cyclizations via Sila-Pummerer Reactions... 

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