Heteroaromatics annulation

The Junjapjpa-Ila (JI)-Heteroaromatic Annulation A New General a-Oxoketene Dithioacetals Mediated Inverse Method for the Synthesis of Benzo/Condensed Heterocycles and Related Heteroaromatization Processes... 

The synthetic strategies depicted in the Scheme 1 provide an overall view of the scope and potential of Jl-heteroaromatic annulation protocol to yield benzoheterocycles with full regiocontrol on all the four positions of the newly formed benzene ring. 

The a-oxoketene dithioacetals 6 (6.1-6.43) employed in this work as three carbon 1,3-biselectrophilic components have been drawn from various active methylene ketones and are described in the Table-1. The corresponding a-oxoketene N,S- and 0,S-acetals (17.1- 17.15) which are usually derived from a-oxoketene dithioacetals are described in Table-2. These examples are only a representative groups to demonstrate the general application of the new Jl-heteroaromatic annulation methodology... 

The versatility of Jl-heteroaromatic annulation has been further established by its application to the synthesis of isomeric benzo[b]thiophenes 58 and 60 <00T8153>. Both 2-cyanomethyl- (57) and 3-cyanomethyl- (59) thiophenes isomers have been reacted with various oxoketene dithioacetals 6 to obtain wide range of 4,5- (58) and 6,7- (60) substituted and condensed benzothiophenes <81AHC171 90JCSP(I)2909> in excellent... 

The above examples represent Jl-heteroaromatic annulation involving the reaction of allyl anions whose double bond is a part of the heterocyclic ring system (Scheme 1). The corresponding a-oxoketene dithioacetals (1,3-electrophilic component) were generally derived from nonheterocyclic carbonyl precursors. Alternatively the Jl-heteroaromatic annulation can also be employed to a-oxoketene dithioacetals derived from heterocyclic ketones (1,3-bielectrophile) and hetero/nonheteroallyl anions (1,3-binucleophile). These reactions are described below. 

Heteroaromatic Annulation with Cyclic Azaallyl Anions Synthesis of Bridgehead Nitrogen Heterocycles... 

In this chapter we outline advances in the ruthenium-mediated alkyne [2 + 2 + 2] cycloaddition reactions. These can be classified into two major categories in terms of the types of products (1) syntheses of benzene derivatives via alkyne [2 + 2 + 2] cycloadditions and (2) syntheses of heteroaromatics via [2 + 2 + 2] cocycloadditions of alkynes with nitriles or heterocumulenes. Benzene ring-forming reactions are essentially prototypes of the corresponding heteroaromatic annulations. Therefore, the first class of reactions is reviewed in the next section and followed by a discussion of the second class of reactions. The mechanistic aspects and synthetic applications of ruthenium-catalyzed [2 + 2 + 2] cycloadditions are also described to exemplify the scientific and practical significance of ruthenium catalysis. 

Readily measurable fluorescence intensities are found for molecules having aromatic and heteroaromatic rings, in particular when annulated rings are present, and in the case of conjugated 7x-electron systems. If the polymer molecules contain such fluorescence-active subunits they can be characterized by this technique, either directly via their fluorescence spectrum or via fluorescence quenching experiments (for polymers with appropriate quencher groups). It is... 

Aromatic and heteroaromatic rings can participate effectively in the 8ir electrocyclization of nitrones. Upon thermal activation, the benzo derivative 130a did not produce the expected products (92TL61).The conversion of the other derivatives 130b-f at 420°C did, however, give the annulated pyrrole 132 and pyridone 133 derivatives, via the intermediates 131, along with some minor by-products (Scheme 38) (94CB247). 

The annulated ring in type C carbonyl ylides 152, generated from oxi-ranes 151, can be heteroaromatic (furo- or thieno-), and the products 153 have good Diels-Alder reactivity, functioning as o-quinodimethane heteroanalogs (Scheme 46) [88AG(E)568 93CB975],... 

Transition-metal-catalyzed annulation reactions of anilines with tertiary amines is another protocol for the catalytic functionalization of sp- C-H bonds (Eq. 45). Several reaction systems resulting in the formation of heteroaromatic compounds which are modifications of the preceding annulation reaction using aniline and ethylene with the aid of rhodium catalyst [71] have recently been developed [72]. 

From the standpoint of biological activity, fused heteroaromatic systems are often of much greater interest than the constituent monocyclic compounds. The appearance of qualitatively new properties of an annulated molecule, enlargement of the possibility of varying pharmacophore groups in different positions of the molecule, and the ability of the latter to interact with a wider spectrum of receptors adopting various conformations are apparently of crucial importance. In addition, the structure of the molecule can be varied due to annulation at different positions of individual heterocyclic fragments. 

Radical-mediated oxidative annulation of heteroaromatic compounds 03S803. 

Rearrangements of divinylcyclopropanes in which one of the vinyl groups constitutes a part of an aromatic or heteroaromatic system, such as 3 or 6, are also known. The initially formed cycloheptadienes (e.g. 4) isomerizes into conjugation in those cases where a reconstitution of aromaticity results, thus providing cycloheptadienes 5 and 7, respectively, annulated with the aromatic ring. 

Those yzurz-annulated heterocycles with a closed rc-system that possess a double bond or another tt- or /z-clcclron bridge situated in the pczz-position of the naphthalene ring opposite to the heterocycle should be set apart. Examples include the Idzi-electron /zcrz-fused heterocyclic acenaphthylene derivatives XII and XV, whose 14 p- and rc-clcclrons are situated on the perimeter of the heteroaromatic skeleton forming an aromatic contour (according to Huckel), while two re-electrons occupy an internal orbital. 

A useful reaction for the synthesis of unsaturated seven-membered heterocycles is the (2 + 2)-cycloaddition of heteroaromatic compounds, e.g., 1 //-pyrrole, furan, or thiophene derivatives, with acetylenes. In combination with a subsequent intramolecular (2 + 2)-cycloreversion (Section IV,B,2) of the annulated cyclobutene moiety, ring enlargement with two carbon atoms can be achieved. 1-Heterocycloheptatrienes, such as benzol6]azepines,26,27,65,66 benzo[fc]oxepins,67,68 benzo[6]-thiepins,69,70 and thiepins,18,71 have been successfully prepared in this way other routes are either nonexistent or laborious.72 In these compounds the reacting carbon-carbon double bond constitutes part of a (4n + 2)7r-electron system and in the (2 + 2)-cycloaddition the resonance energy of the aromatic nucleus is lost. Just like the nonaromatic heterocycles, heteroaromatic compounds have been reported to undergo (2 + 2)-cycloaddition reactions both with electron-deficient and with electron-rich acetylenes. 

Annulation can take place with virtually any rt-system attached to a carbene C-atom, including a variety of aromatic, heteroaromatic, and simple vinyl systems [Eqs. (2)-(4)] [15]. 

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