Toward electrophilic reagents alkylation

Alkyl substituents in aromatic azoloazines are reactive towards electrophilic reagents in basic media. Basic reagents readily abstract protons from such alkyl groups yielding resonance stabilized carbanions. Thus, treatment of the methyl derivatives (243) with aldehydes gives the alkenes (245) (Scheme 21) <84H(22)174i). Ready formation of the resonance stabilized anions (244) is behind the activity of the methyl group. 

In the case of N-vinylpyrroles containing donor (alkyl) substituents, the yields of formylpyrroles are significantly reduced (17%-56%). This could be explained by the fact that aromatic substituents decrease the sensitivity of the N-vinyl group toward electrophilic reagents. 

There are a wide variety of methods for introduction of substituents at C3. Since this is the preferred site for electrophilic substitution, direct alkylation and acylation procedures are often effective. Even mild electrophiles such as alkenes with EW substituents can react at the 3-position of the indole ring. Techniques for preparation of 3-lithioindoles, usually by halogen-metal exchange, have been developed and this provides access not only to the lithium reagents but also to other organometallic reagents derived from them. The 3-position is also reactive toward electrophilic mercuration. 

As shown m Table 6 4 electron releasing alkyl groups on the double bond increase the rate of epoxidation This suggests that the peroxy acid acts as an electrophilic reagent toward the alkene... 

Pyridine lies near one extreme in being far less reactive than benzene toward substitution by electrophilic reagents. In this respect it resembles strongly deactivated aromatic compounds such as nitrobenzene. It is incapable of being acylated or alkylated under Friedel-Crafts conditions, but can be sulfonated at high temperature. Electrophilic substitution in pyridine, when it does occur, takes place at C-3. 

Perfluoroalkyl(phenyl)iodonium sulfonates 42 (also known as FITS reagents), as well as lFf,lff-perfluoroalkyl(aryl)iodonium triflates 44, have found practical application as electrophilic fluoro alkylating reagents toward a... 

Substituted imidazole 1-oxides 228 are predicted to be activated toward electrophilic aromatic substitution, nucleophilic aromatic substitution, and metallation as described in Section 1. Nevertheless little information about the reactivity of imidazole 1-oxides in these processes exists. The reason for this lack may be the high polarity of the imidazole 1-oxides, which makes it difficult to find suitable reaction solvents. Another obstacle is that no method for complete drying of imidazole 1-oxides exists and dry starting material is instrumental for successful metallation. Well documented and useful is the reaction of imidazole 1-oxide 228 with alkylation and acylation reagents, their function as 1,3-dipoles in cycloadditions, and their palladium-catalyzed direct arylation. 

The Sn-S, Sn-Se, and Sn Te bonded compounds are less reactive than Sn-O bonded species, e g. towards water. Reactions proceed with a variety of electrophilic reagents (e.g. alkyl halides, halogens, and snlfur(n) halides). 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

Additional flexibility in the control over the selectivity of heterolytic reactions is provided in the diversity of electrophilic reagents that formally correspond to the same electrophile. For example, reagents such as RCO BF, RCOO-SO2CF3, RCOCl, and (RC0)20 are employed in synthesis as equivalents of the acyl cation RCO. However, a tremendous difference in the reactivity of these acylating species enables one to choose a reagent specifically adjusted to the peculiarity of the nucleophilic counterpart. In a similar way, such unlike compounds as trialkyloxonium salts, R30 BF7, alkyl halides, tosylates, or acetates can serve as transfer agents of the same alkyl cation, R, but they differ drastically in their activity and pattern of selectivity toward various nucleophiles. 

Vinylcopper reagents react with a wide variety of electrophilic reagents such as halogens, alkyl halides, allylic halides, acid chlorides, epoxides, a,(3-unsaturated ketones, and a,p-acetylenic esters with complete retention of the double bond stereochemistry. To enhance the reactivity of vinylcopper intermediates toward carbon electrophiles, the coupling is often carried out in the presence of activators such as HMPT, DMPU, and/or P(OEt)3 (triethylphosphite). Some representative examples of stereospecific... 

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