Heterocyclic substrates

Furans, thiophenes and pyrroles have all been obtained by addition of alkynic dienophiles to a variety of other five-membered heterocycles, as illustrated in Scheme 104. As the alkynic moiety provides carbons 3 and 4 of the resulting heterocycle, this synthetic approach provides an attractive way of introducing carbonyl containing substituents at these positions, especially as many of the heterocyclic substrates are readily generated. Such reactions do... 

Perfluoroalkylation of substituted benzenes and heterocyclic substrates has been accomplished through thermolysis of perfluoroalkyl iodides in the presence of the appropriate aromatic compound Isomeric mixtures are often obtained W-Methylpyrrole [143] and furan [148] yield only the a-substituted products (equation 128) Imidazoles are perfluoroalkylated under LTV irradiation [149] (equation 129). 4-Perfluoroalkylimidazoles are obtained regioselectively by SET reactions of an imidazole anion with fluoroalkyl iodides or bromides under mild conditions [150] (equation 130) (for the SET mechanism, see equation 57)... 

A few studies on solvolyses by alcohols and by water are available. The hydrolyses studied include displacement of alkylamino groups from acridine antimalarials and of halogen from other systems. In all cases, these reactions appeared to be first-order in the heterocyclic substrate. By a detailed examination of the acid hydrolysis of 2-halogeno-5-nitropyridine, Reinheimer et al. have shown that the reaction rate varies as the fourth power of the activity of water, providing direct evidence that the only reactive nucleophile is neutral water, as expected. 

It has also been argued10,40 that the second mechanism (rapid, reversible interconversion of II and IV) cannot be general. The basis for this contention is the fact that electrophilic catalysis is rare in nucleophilic aromatic substitution of non-heterocyclic substrates, an exception being the 2000-fold acceleration by thorium ion of the rate of reaction of 2,4-dinitrofluorobenzene with thiocyanate... 

Scheme 9.16 Baeyer-Villiger biooxidation of heterocyclic substrates.

There is clearly enormous potential using other cis dihydrodiols produced from benzocyclo-alkenes, or from the numerous dihydrodiols produced from polycyclic carbocyclic and heterocyclic substrates. 

A number of compounds have been prepared by a double intramolecular cyclization of a substituted six-membered heterocyclic substrate. Examples of this strategy are summarized in Scheme 15 and Equation (14). The... 

A number of molybdenum-containing hydroxylases catalyzing the first hydrox-ylation step of N-containing compounds have been characterized thoroughly (e.g., carbazole [314], quinoline [327], and indole [350]). The enzyme s redox-active has been described as a molybdenum ion site coordinated to a distinct pyranopterin cofactor (two different [2Fe2S] centers) and in most cases, flavin adenine dinucleotide centers. This active center transfers electrons from the N-heterocyclic substrate to an electron acceptor, which for many molybdenum hydroxylases is still unknown [350],... 

It has been inferred that acetone adds reversibly across the S=C—S grouping to give hetero-pentalene-type adducts (110) and (111) which maintain an equilibrium between the two heterocyclic substrates (108) and (109) (Scheme 22) <92JHC69). 

The asymmetric Horner-Wadsworth-Emmons (HWE) reaction of l,3-dioxan-5-ones with phosphonate 184 and a chiral diamine was reported. With the /i r/-butyl-substituted l,3-dioxan-5-one, the product possesses a chiral axis. It was obtained in good yield and with 80% ee (Scheme 53) <2002TL281>. The HWE reaction with similar heterocyclic substrates was used to provide conformationally restricted arachidonic acid derivatives <1999TA139>. 

Heterocyclic substrates in SET processes have been widely studied, including the reactions of diliydroiiicotiiiamide,116 pyridine, and quinoline117 and also phenoxazine and phenotiiiazines.118 Phenothiazine has also been shown by ESR analysis to undergo an electron-transfer reaction witii its radical cation with an appreciable 15N/14N isotope effect.119 The reaction of phenazine di-A -oxidc radical cations with hydrocarbons shows evidence of non-radical processes.120... 

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