Heterocycles SrnI reaction

Crozet and co-workers have used S l reactions for synthesis of new heterocycles, which are expected to be biologically active (see also Section 7.3, which discusses synthesis of alkenes). For example, 2-chloromethyl-5-nitroimidazole reacts with the anion of 2-nitropropane to give 2-isopropylidene-5-nitroimidazole. It is formed via C-alkylation of the nitronate ion followed by elimination of HN02 (Eq. 5.33).51a Other derivatives of nitroimidazoles are also good substrates for SrnI reactions.5113 0... 

Crozet and coworkers have used SrnI reactions followed by elimination of HN02 for the synthesis of various new heterocyclic compounds substituted with alkenyl groups. These compounds are expected to be important for pharmaceutical use (see Eq. 7.139).185... 

JCS(P1)249>. In an interesting alternative to direct acylation of this heterocycle, Pierini and Rossi examined the photostimulated SrnI reaction of the enolate of 2-acetyl-1-methylpyrrole 36 with haloarenes (e.g., iodobenzene, 37) as well as neopentyl iodides to afford a-substituted acetyl pyrroles 38 <99JOC6487>. 

Although the SRNi reaction is of considerable utility in heterocyclic synthesis (80JOC1546, 80TL1943), its scope is restricted by the poor... 

Other radical methods for heterocycle synthesis involve SrnI reactions. The synthesis of indoles [95BCSF306], imidazoles [95JOC8015], imidazopyrimdines [95T9643], and substituted 1,3-dioxanes [95JCS(P1)609] have been reported. 

The Srn 1 reaction has been applied to heterocycles. Among five-membered ring compounds, halothiophenes have been the most studied they have been shown to be susceptible to both electron-stimulated and photostimulated reactions, and have been converted to the corresponding acetonitriles [150], acetones [151], and phenyl-sulfides [ 152] in low to medium yields. In the study with the benzenethiolate anion it has been shown that the yield is low because of fragmentation of the adduct radical anion it can be increased by adding an electron acceptor, e.g. benzonitrile which prevents decomposition. Further applications include the thermally activated SrnI reaction between 3-iodobenzothiophene and enolates [153] and the photo-stimulated reaction of 3-halo-2-aminobenzothiophenes [154]. 

SrnI reactions in syntheses of benzo-annelated heterocycles 84BSB547. Stereo- and regioselective syntheses of natural saturated heterocycles... 

Although the intramolecular SrnI reaction has been studied to a lesser extent as compared to the intermolecular process, it has been shown to represent a highly useful route for the synthesis of various heterocyclic compounds. For example, the SrnI cyclization of N-alkyl-N-acyl-o-haloaniUnes and N-acyl-N-methyl-o-chlorobenzylamines (Equation 13.5) gives N-aUcylindol-2-one and 1,4-dihydro-2H-isoquinolin-3-ones in moderate to good yields [21]. lodoketone 1 reacts under SrnI conditions to provide the complex heterocyclic compound 2 with excellent yield (Equation 13.6) [22]. 

Just as in aryl halides, the halogen can be replaced by hydrogen and by a metal, or be involved in transition metal-catalyzed processes (covered in Section 3.2.3.11.2). Three of the mechanisms of such nucleophilic substitutions are familiar from benzene chemistry via arynes, SrnI processes, and Pd(0)-catalyzed sequences. However, of the two further mechanisms of nucleophilic replacement, the ANRORC (Addition of Micleophile, Ring Opening, Ring Closure) is unique to heterocycles, and Sae reactions occur only with strongly activated benzenoid systems. 

Intramolecular photochemical dehydrohalogenation reactions have featured prominently in heterocyclic and carbocyclic synthesis. The novel photocyclization of the enamine (110) was the key reaction in the synthesis of the antileukaemic lignan steganacin (111) (Scheme 36). This cyclization could have occurred by the SrnI mechanism. ... 

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