Indole anion

The nucleophilicity of the nitrogen atom survives in many different functional groups, although its basicity may be lost. Reactions of non-basic, but nucleophilic urea nitrogens provide, for example, an easy entry to sleeping-pills (barbiturates) as well as to stimulants (caffeine). The nitrogen atoms of imidazoles and indole anions are also nucleophilic and the NH protons can be easily substituted. 

Alkylation can also be accomplished with electrophilic alkenes. There is a dichotomy between basic and acidic conditions. Under basic conditions, where the indole anion is the reactive nucleophile, A-alkylation occurs. Under acidic conditions C-alkylation is observed. The reaction of indole with 4-vinylpyri-dine is an interesting illustration. Good yields of the 3-alkylation product are obtained in refluxing acetic acid[18] whereas if the reaction is done in ethanol containing sodium ethoxide 1-alkylation occurs[19]. Table 11.2 gives some examples of 3-alkylation using electrophilic alkenes. 

A AlI lation. 1-Substitution is favored when the indole ring is deprotonated and the reaction medium promotes the nucleophilicity of the resulting indole anion. Conditions which typically result in A/-alkylation are generation of the sodium salt by sodium amide in Hquid ammonia, use of sodium hydride or a similar strong base in /V, /V- dim ethyl form am i de or dimethyl sulfoxide, or the use of phase-transfer conditions. 

The most functionalized mitomycin precursor was synthesized by Dong and Jeminez <1999JOC2520> in a racemic form, starting from indolic anion 266 and vinylsulfonium salts (route a) they also explored a diastereoselective version of this synthesis by using enantiopure vinylsulfonium salts, which gave low asymmetric induction <2001TA999>. 

The existence of an intermediate species in the dioxygen transfer from 4a-hydroper-oxyflavin anion to phenolate and indole anions has previously been shown and ab initio and semiempirical MO calculations have been used to examine possible candidates for... 

The indole anion is resonance stabilized, with negative charge localized mainly on nitrogen and C-3. It can now participate as a nucleophile, e.g. in alkylation reactions. However, this can lead to iV-alkylation or C-alkylation at C-3. Which is the predominant product depends upon a number of... 

The reaction of the pyrrole and indole anions with electrophiles are discussed in Section 3.3.1.3.1. 

As in pyrrole, H NMR has been used to explore the nature of the indole anion with a range of counter cations, including indole Grignard reagents. H NMR data for Li+ and... 

Nitro-l-(phenylsulfonyl)-l//-indole 829 undergoes nucleophilic addition reactions with enolates of diethyl malonate and cyclohexanone, lithium dimethylcuprate (Scheme 159), and indole anion (Equation 209) to afford the corresponding 3-substituted 2-nitroindoles in low to high yields <1997TL5603, 1999TL7615>. 

Absorption Spectra of Isoconjugated Systems of the Indole Anion... 

S.S kcal/mol, so that facile conformational change from 81s to 81u could be expected. Actually, koumine (70) was obtained in 80% yield, when the indole anion prepared from the 18-O-acetate (82) was treated with 0.1 eq of Pd(OAc)2 and 0.5 eq of triphenylphosphine at 80-90°C. 

Figure 2 Orientations of indole anions in the solid state.

A-Acyl groups can be introduced by reaction of pyrrole or indole anions with acyl halides in THE <8713689,88CPB3770,88JOM209> or under phase transfer conditions (Equation (67)) <815461 >. 

Both pyrrole and indole anions are sufficiently nucleophilic to react with Michael acceptors such as unsaturated esters, ketones and nitriles. When the reaction is done under alkaline conditions the alkylation usually occurs at nitrogen. Pyrrole and indole are also reactive Michael acceptors under... 

W-Deprotonated indole anions give the 1-substituted indoles with these reagents [307]. 

Ylides derived from imidazolium- and triazolium-substituted indole anions belong to the class of conjugated mesomeric betaines. Their tautomers are N-heterocyclic carbenes, which undergo trapping reactions with sulfur, selenium, and triethylborane, respectively. Deprotonation of the salts 45a—c with NaOH/EtOH produces the ylides 46a—c which are in tautomeric equihbrium with carbenes 47a—c (Scheme 36) (2014T8672). 

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