Electron-rich aromatic heterocycles

An analogous reaction is the Houben-Hoesch reaction,(sometimes called the Hoesch reaction) using nitriles 7 to give aryl ketones 8. This reaction also is catalyzed by Lewis acids often zinc chloride or aluminum chloride is used. The Houben-Hoesch reaction is limited to phenols—e.g. resorcinol 6—phenolic ethers and certain electron-rich aromatic heterocycles ... 

A mixture of anhydrous lithium nitrate and trifluoroacetic anhydride in acetonitrile in the presence of sodium carbonate has been used to convert alcohols to nitrate esters for a range of peptide, carbohydrate and steroid substrates. Yields are good to high but products need puritication to remove trifluoroacetate ester impurities, which can be signiflcant in the absence of the carbonate. A similar system used for the nitration of electron-rich aromatic heterocycles employs trifluoroacetic anhydride with ammonium or potassium nitrate. ... 

Thiophene (see Fig. 2), a five-membered aromatic ring containing sulfur, is comparable in structure to pyrrole and furan, which contain nitrogen and oxygen, respectively, but it possesses some unique qualities. Sulfur is an electron-donating heteroatom and it contributes two electrons to the 6jt electron-system of the ring and additionally has a lone pair of electrons in an sp -hybridized orbital, in the plane of the ring. Thiophene is thus an electron-rich aromatic heterocycle. 

The classical Vilsmeier-Haack reaction is one of the most useful general synthetic methods employed for the formylation of various electron rich aromatic, aliphatic and heteroaromatic substrates. However, the scope of the reaction is not restricted to aromatic formylation and the use of the Vilsmeier-Haack reagent provides a facile entry into a large number of heterocyclic systems. In 1978, the group of Meth-Cohn demonstrated a practically simple procedure in which acetanilide 3 (R = H) was efficiently converted into 2-chloro-3-quinolinecarboxaldehyde 4 (R = H) in 68% yield. This type of quinoline synthesis was termed the Vilsmeier Approach by Meth-Cohn. ... 

The bis-indole diphosphine delivers the best ee and as the heterocyclic units are also electron rich aromatics this also gives the added advantage of the highest activity of the catalyst system. This overcomes one drawback often encountered, that high hydrogen pressures are frequently needed for ruthenium-based catalysts. 

Most reactions discussed in this chapter rely on the formal attack of an electrophilic organometallic species on the electron-rich aromatic core of a five membered heterocycle. Depending on the way the transition metal... 

The acid-catalyzed dimerization of pyrroles and indoles also involves electrophilic attack by the 2H- or 3//-protonated species upon the non-protonated heterocycles (Schemes 6, 7 and 8, Section 3.05.1.2.2), and 3,3-dimethyl-3//-indole has been reported to react with 7r-electron-rich aromatic compounds to yield the 2-ary.l-3,3-dimethyl-2,3-dihydroindoles (77S343). In the absence of a nucleophile strong acids promote the interchange of substituents at the 2- and 3-positions of 2,3,3-trisubstituted 3//-indoles, e.g. (510) (511) (62JOC1553). 

Three years earher, in 1972, Banister had proposed that planar S-N heterocycles belong to a class of electron-rich aromatics , which conform to the Hiickel (4n 2) TT-electron rule. These two aspects of S N... 

N-Acyliminium ions are versatile intermediates in organic synthesis they not only react with various nucleophiles such as electron-rich aromatic and heteroaromatic compounds but also undergo cycloaddition reactions with unsaturated compounds.It is especially noteworthy that N-acyliminium ions serve as electron-deficient 4t7 components in [4 + 2] cycloaddition with alkenes and alkynes. " This reaction serves as a useful method for the construction of heterocyclic rings containing a nitrogen atom. Acyclic structures containing amino and hydroxyl groups can also be synthesized from the initially formed cyclic compounds. 

The ability of boranes to coordinate and activate an incoming substrate was also proposed recently by Lu and Williams.The di(pyrazolyl)borohydride was first coordinated to mthenium. Chloride abstraction in acetonitrile then afforded the imido complex 46c as a result of intramolecular hydroborafion of the CN triple bond (Scheme 15). The process is amenable to catalysis using excess of NaBH and 1 equiv. of NaOfBu (Table 1). A broad variety of electron-poor and electron rich-aromatic nitriles were thereby reduced into primary amines using 5 mol% of 46c. With electron-rich heterocycles, hydration instead of hydrogenation is observed and amides are obtained. 

Addition of electron-rich aromatic systems to the 1,2,4-triazine ring can easily be achieved by preliminary activation of the heterocyclic system by protonation or alkylation. Addition of the following nucleophiles to the 1,2,4-triazinium ion (129) has been observed indoles, pyrroles, anilines, phenols, and aminothiazoles. The 1,6-dihydro-1,2,4-triazines (130) can be isolated in most cases and oxidized in a second step to the aromatic 1,2,4-triazine system (Scheme 20). 1,2,4-Triazin-5(2i/)-ones also undergo this reaction. 5-Unsubstituted 1,2,4-triazine 4-oxides (131) can be transformed into 5-substituted 1,2,4-triazine 4-oxides (Equation (14)) <86KGS1535, 92H(33)93l, 95UP 611-01>. 

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