Electron-rich heterocycles

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

The site of dihydroxylation in heterocycles depends on the nature of the heteroaromatic system (Scheme 9.31) usually, electron-rich heterocycles like thiophene are readily biooxidized but give conformationally labile products, vhich may undergo concomitant sulfoxidation [241]. Electron deficient systems are not accepted only pyridone derivatives give corresponding cis-diols [242]. Such a differentiated behavior is also observed for benzo-fused compounds biotransformation of benzo[b] thiophene gives dihydroxylation at the heterocyclic core as major product, while quinoline and other electron-poor systems are oxidized at the homoaromatic core, predominantly [243,244]. 

Coupling reactions with diazonium salts to yield intensely colored azo derivatives have often been used for the detection of phenols, primary aromatic amines and electron-rich heterocyclics. 

A different approach for the modification of the basic Malachite Green lactone structure has been the replacement of one 4-dimethylaminophenyl group by electron-rich heterocycles. The most thoroughly investigated heterocycle has been the 3-indolyl residue, which may be introduced by two different routes as shown in Scheme 7. 

Reaction of the indolylbenzoylbenzoic acid with electron-rich heterocycles other than indoles has also produced a number of novel color... 

Electron-rich heterocyclic systems such as indolizines react readily with DEAZD (and PTAD) to give substitution products (Eq. 16).141 None of the formal [8 + 2] cycloaddition products (e.g., 89) are observed. This is in direct contrast to the reaction of indolizines with electrophilic acetylenes which gives high yields of cycloaddition products, presumably via a stepwise mechanism, in the presence of palladium on charcoal.142 This example of... 

A wide variety of cyclic S-N compounds containing two or three coordinate sulfur is known (i ), The binary S-N rings vary in size from four (S2N2) to ten (SsNs" ") atoms and examples of anions (SsNs") and cations (S3N2 , S N3 , S N ) are known in addition to neutral molecules (2). The excess of electrons in these planar, electron-rich heterocycles is often accommodated in low lying tt orbitals but, in some cases (e.g. S N, S Ns"), the number of tt electrons is reduced by formation of transannular S-S bonds to give cages ( , ). 

Electron-rich heterocycles, snch as pyrrole and furan, bear more resemblance to car-bocyclic rings their side chains are mnch less acidic, and undergo lateral lithiation mnch less readily. Without a second directing group, methyl groups only at the 2-position of fnran, pyrrole or thiophene may be deprotonated. 

The term charge tranter refers to a succession of interactions between two molecules, ranging from very weak donor-acceptor dipolar interactions to interactions that result in the formation of an ion pair, depending on the extent of electron delocalization. Charge transfer (CT) complexes are formed between electron-rich donor molecules and electron-deficient acceptors. Typically, donor molecules are p-electron-rich heterocycles (e.g., furan, pyrrole, thiophene), aromatics with electron-donating substiments, or compounds... 

Electrophilic aromatic substitution Electrophilic aromatic substitution of indole occurs on the five-membered pyrrole ring, because it is more reactive towards such reaction than a benzene ring. As an electron-rich heterocycle, indole undergoes electrophilic aromatic substitution primarily at C-3, for example bromination of indole. 

Electron-rich heterocycles can also be coupled with olefins in the presence of a suitable palladium(II) catalyst. The oxidative coupling requires the use of a stoichiometric amount of palladium however, unless a suitable oxidising agent is added to the reaction. In an early example N-sulphonylated pyrrole was reacted with 1,4-naphthoquinone in the presence of an equimolar amount of palladium acetate to give the coupled product in good yield (6.92.).124... 

Alkylation of tt-Electron-rich Heterocyclic Compounds with Electrophilic Olefins G. V. 

Nucleophiles other than hydride can be added to support-bound imines to yield amines. These include C,H-acidic compounds, alkynes, electron-rich heterocycles, organometallic compounds, boronic acids, and ketene acetals (Table 10.9). When basic reaction conditions are used, stoichiometric amounts of the imine must be prepared on the support (Entries 1-3, Table 10.9). Alternatively, if the carbon nucleophile is stable under acidic conditions, imines or iminium salts might be generated in situ, as, for instance, in the Mannich reaction. Few examples have been reported of Mannich reactions on insoluble supports, and most of these have been based on alkynes as C-nucleophiles. 

Although the NBS-silica system has useful potential for bromination of electron rich heterocycles, it has limited application to non-acdvated aromatics and sometimes meets problems with polybromination even for the activated heterocycles. Thus, it was of interest to investigate the potential of different brominating agents and different solids. Bromination of anisole with... 

In order to outline the scope of this chemistry, Sections 4.8.2 and 4.8.3 will discuss the catalysts and carbenoid precursors used. This will be followed by reactions of caibenoids with ir-systems, organized according to the ir-system involved, alkenes (Section 4.8.4), alkynes (Section 4.8.5), benzenes and electron-rich heterocycles (Section 4.8.6). Particular emphasis will be placed on the stereochemical outcome of these reactions with reference to applications in organic synthesis. 

The Vilsmeier-Haack reaction (herein, Vilsmeier reaction ) provides an effective method for the formylation of aromatic systems. The combination of phosphoryl chloride with V-methylaniline or dimethylformamide generates an iminium phosphorus derivative or chloro-iminium cation that is the active electrophile in an electrophilic substitution reaction. The resulting substitution product is an iminium salt 1, which is hydrolyzed on workup with alkali to give the carbaldehyde product 2 (Scheme l).1,2 The method is particularly useful with activated arenes or electron-rich heterocycles, such as pyrroles, furans, thiophenes, and indoles. We had a special interest in the preparation of indole-7-carbal-dehydes, namely, their properties as isosteres of salicylaldehyde. Thus, we became involved in a wide-ranging investigation of 4,6-dimethoxy-... 

A consequence of this delocalisation is that the lone pair is not available for protonation under moderately acidic conditions so, like pyrrole, indole is another weakly basic heterocycle. Another similarity to pyrrole is that being an electron-rich heterocycle indole easily undergoes aromatic electrophilic substitution, and is also rather unstable to oxidative (electron-loss) conditions. However, an important difference emerges here, in that whereas pyrrole preferentially reacts with electrophiles at the C2/C5 positions, indole substitutes selectively at the C3 position. The reasons for this will be discussed later. 

As an electron-rich heterocycle, indole easily undergoes electrophilic substitution. However whereas pyrrole reacts preferentially at the C2/C5 positions (see Chapter 2), indole reacts preferentially at the C3 position. 

The parent A,B-diheteropentalenes possess differing degrees of aromaticity based upon chemical behavior such as their ability to undergo substitution reactions with electrophilic reagents. They belong to the electron-rich heterocycles, but a quantification of their relative aromaticities is less easily resolved. The wide range of potential criteria available for this purpose has been surveyed < 84CHEC-I(4) 1037). 

Formyl derivatives of diazaheteroaromatic compounds would be expected to be hydrated, but in this case the nucleus would also be reducible carbonyl derivatives of Tr-electron-rich heterocyclic compounds would be expected to behave pretty much as the corresponding benzene derivatives. 

Several enzymes that halogenate organic substrates are well known and these enzymes have been studied extensively, especially those involving alkenes, alkynes, active methylene compounds, electron-rich heterocycles (pyrroles, indoles), and phenols [1,103-105]. Both chloroperoxidase and bromoperoxidase are widespread in the... 

Thiophene is an aromatic compound. Its structure can be assumed to be derived from benzene by replacement of two annular CH groups with sulfur. The sulfur atom in this five-membered ring acts as an electron-donating heteroatom by contributing two electrons to the aromatic sextet and thiophene is thus considered to be an electron-rich heterocycle. 

---