Oxygen containing heterocycles functionalization

This section covers the synthesis of aziridines, oxiranes, /J-lactams and oxetanes. Aziridines are fairly important moieties in bioactive molecules and thus new routes for their synthesis are constantly being developed. /1-Lactams are probably the most important heterocyclic compounds that contain a single nitrogen atom, due to their importance in penicillin and cephalosporin chemistry. Their synthesis and chemistry has received much attention and much of this work has been reviewed544. The oxygen-containing heterocycles are much less commonly synthesized from double-bonded functional groups. 

There are several reactions (bromination, oxymercuration, epoxidation) of olefinic hydroxy and epoxy compounds in which the oxygen function can react intramolec-ularly with an intermediate formed at the double bond, leading to an oxygen-containing heterocyclic compound (tetrahydrofuran or tetrahydropyran) (Scheme 6). 

Chromones (4f -chromen -ones, 4//-l-benzopyran-4-ones) are naturally occurring oxygen-containing heterocycles which perform important biological functions in nature [46]. Many chromone derivatives, including flavones and 2-(trifluoromethyl)... 

Palladium-catalyzed C-H olefination is also a very useful protocol to synthesize oxygen-containing heterocycles, since it allows to functionalize the substrates with an unsaturated olefinic moiety which would constitute a Jt-conjugated structure or be elaborated further. Two pathways are often encountered in this approach (i) addition of the resulted arylpalladium complex to alkynes and subsequent protonation or transformation and (ii) addition of the arylpalladium complex to olefins and following palladium hydride elimination [7b, 20]. The current methods are mainly focused on the functionalization of aromatic C-H bonds to form benzo-oxacycles. 

Based on the rapid development of C-H activation in the past few decades, palladium-catalyzed synthesis of oxygen-containing heterocycles via C-H activation has been obtained a significant progress in turn, these achievements also promoted the advance of transition metal-catalyzed C-H functionalization. A broad scope of oxacycles has been synthesized via this approach. Some of these structures are even difficult to access through the conventional methods and hence highlight the palladium-catalyzed C-H activation a powerful and efficient method to achieve novel transformations. 

Containing heterocycles are important substructures found in numerous bioactive natural products and important pharmaceuticals. The diversity of the structures encountered, as well as their biological and pharmaceutical relevance, has motivated research aimed at the development of new economical, efficient, and selective synthetic strategies to access these compounds [2, 3]. For the past dozen years, spectacular achievements have been made toward the synthesis of oxygen-containing heterocycles via Au- and Pt-catalyzed C-H activation/functionalization proce ss. 

Hybrid compounds containing heterocyclic nitramine and em-dinitro functionality represent a class of high performance energetic materials. Such compounds frequently exhibit higher heats of formation, crystal density, detonation velocity and pressure, and better oxygen balance compared to analogous aromatic compounds. 

Besides N-acylated enamines, enamides containing a functional group in the carbon skeleton are obtained in the acid-catalyzed reactions of carbonyl compounds with nitriles. Some of them were shown in equations 18, 28, 31, 33, 38, 58, 59, 63, 65, 75 and 87 and they are mainly the polyacylated enamines (e.g. /Lacylaminovinyl ketones 79, 87, 93, 200, 207 and 278). Most of them are intermediates in the synthesis of oxygen and nitrogen containing heterocycles or products of further conversions of the latter. 

Abstract Carbon d ylide dipoles are important intermediates with great application in heterocyclic chemistry. Here, we show how the rhodium-catalyzed a-diazocarbonyl compounds are employed in the generation of carbonyl ylides and their effective use for the synthesis, as well as functionalization, of heterocycles. Herein we discuss recent advancements in this field mainly describing the synthesis and importance of various oxygen-and nitrogen-containing heterocyclic systems and natural products from a-diazocarbonyl compounds. 

A large number of heterocyclic compounds of oxygen, nitrogen, and sulfur are prepared by condensation of di- or poly-functional compounds. Nitrogen-containing heterocycles by the thousands have been prepared by such reactions. The simplest such reaction is one leading to the preparation of a pyrrolidine or piperidine derivative. The synthesis of pyrrolidine may be accomplished by reaction of ammonia and 1,4-dichlorobutane in a stepwise process that may include an intramolecular displacement of chloride from the aminoalkyl chloride [Eq. (31)] or of ammonia from the aminoalkyl amine hydrochloride" [Eq. (32)] each process is known to occur. 

Imidazopyridines are important nitrogen-containing heterocycles that show a wide range of bioactivities. Hajra and coworkers have developed an iron-catalyzed oxidative diamination of nitroalkene with 2-aminopyridine to access 2-nitro-3-arylimidazo[l,2- ]pyridines under mild and aerobic reaction conditions (Scheme 9.6) [8]. In particular, the method allows the formation of two new C-N bonds through sequential Michael addition and vinyl C(sp )-H/N-H functionalizations and represents the first example of employing molecular oxygen as the terminal oxidant for the selective C-H amination. 

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