Other Heterocydes

Syntheses of the Pyrimidine Ring from Other Heterocydes... 

Thiophene is a usefiil template for four-carbon homologation via reduction [9], as well as a bioisostere of the benzene ring and other heterocydes in medicinal chemistry. Thiophene is a n-electron-excessive heterocycle. It favors electrophilic substitution, which, similar to metalation, takes place preferably at the a-positions due to the electronegativity of the sulfiir atom [10]. In comparison to the oxygen atom in fiiran, the sulfiir atom in thiophene has lower electronegativity, so its lone pair electtons are more effectively incorporated into the aromatic system. The aromaticity of thiophene is in between that of benzene and fiiran. As a consequence, the difference in reactivity of a-halothiophenes and 3-halothiophenes is not as pronounced as that of the corresponding halofiirans. 

An unusual class of Pd-catalyzed [3 + 2] cycloaddition reactions between activated aziridines and heterocumulenes such as isocyanates and carbodiimides has been extensively examined by Alper and coworkers [94]. These transformations led to the preparation of ureas, carbamates, and other heterocydes in good yields. For example, treatment of 138 with phenylisocyanate afforded urea 139 in 72% yield (Eq. (1.55)) [94aj. The mechanism of these reactions presumably involves oxidative addition of the aziridine to Pd , followed by insertion of the isocyanate into the Pd—N bond and C—C bond-forming reductive elimination (similar to the reactions of vinylaziridines described in the section above, although allylpalladium intermediates are obviously not involved). 

Besides the classical heterocydization and ammonolysis methods some other syntheses have been developed to prepare secondary and tertiary... 

Other examples of addition reactions that form carbon-nitrogen bonds are the reactions of hexafluoro-2-butyne with various heterocydes [77], aromatic... 

Various other examples in this chapter have already highlighted how N,N-dimeth-ylformamide dimethyl acetal can be efficiently utilized as a synthon for the construction of heterocydic rings (see Schemes 6.189, 6.194, 6.195, 6.229, and 6.230). West-man and coworkers have described a two-step method for the generation of a wide variety of heterocydic scaffolds, based on the initial formation of alkylaminoprope-nones and alkylaminopropenoates from N,N-dimethylformamide diethyl acetal (DMFDEA) and the corresponding CH-acidic carbonyl compounds (Scheme 6.256)... 

The corresponding bridgehead heterocydes are difficult to obtain by conventional heating methods since the reactions of a-tosyloxyketones with ethylenethioureas remain incomplete in an oil bath. The microwave-accelerated process, on the other hand, gets completed in a short time (Scheme 6.44) [147,148],... 

The transition metal-catalyzed domino reactions will undoubtedly have a splendid future which is underlined by the increasing number of publications in this area Steglich et al. presented an approach to arcyriacyanin A via a domino Heck reaction between a bromo(indolyl)maleiimide and 4-bromoindole.1811 The synthesis of 33 -bifurans by Ling et al. was achieved using a novel palladium-catalyzed domino dimerization and subsequent cyclization of acetylenic ketones.1821 Other applications of a combination of Heck reactions for domino processes are the syntheses of aza-heterocydes developed by our group.1831... 

From the results presented here, one could get the impression that such allenes with hydroxyl groups in the substituents will always form heterocydes in the presence of transition metal catalysts, but in the presence of other substrates even allenylcarbinols can react to give different products. Examples are the rhodium-catalyzed reaction of allenylcarbinol 78 and phenylacetylene 79 to 80 [42], the palladium-catalyzed reaction of 81 and pyrrolidine 82 to 83 [43] and the ruthenium-catalyzed reaction of 78 and 79 to 84, an isomer of the rhodium-catalyzed reaction of the same substrates mentioned above [44] (Scheme 15.19). 

Mild conditions discovered for the cyclization of propargyl pyridine 145 were applied to other substituted and elaborated heterocydes, giving indolizidine-type products in good-to-excellent yields (Table 9.17). 

B, Iddon, Cychxiddition, Ring Opening and Other Novel Reactions of Thiophenes, in Heterocydes, 1983, 20. 1127. 

SYNTHESIS BY TRANSFORMATION OF OTHER HETEROCYCLES 3.12.4.1 Ring Contraction of Six-membered Heterocydes... 

Pyridylaldehydes 161 [67] and other similar heterocyclic aldehydes [68] also participate in the three-component process affording aminomethylpyridine derivatives 163 (Scheme 7.21). This process can be used to generate novel molecules, such as 166, that contain three different heterocydes, each of which is introduced via one of the three components. 

With its sextet of 71 electrons, thiophene possesses the typical aromatic character of benzene and other similarly related heterocydes. Decreasing orders of aromaticity have been suggested to reflect the strength of this aromatic character benzene > thiophene > pyrrole > furan (9) and benzene > thiophene > selenophene > tellurophene > furan (10). 

The benzannulation reaction tolerates phenyl carbene complexes bearing both electron-donating [35a] and -withdrawing [35b] substituents. Additionally, carbene complexes containing condensed systems such as naphthalene and other carbocyclic hydrocarbons as well as heterocydes have also been successfully submitted to the reaction (see Section 8.5). 

The introduction of chirafity into NHCs will therefore follow different strategies than those that have proved to be successful in phosphine-based asymmetric catalysis. For example, N-heterocydic carbene units will not create an edge-to-face arrangement of their aryl substituents, a structural feature common to many chiral diphosphines, such as the derivatives of Diop, Binap, Josiphos, Chiraphos and others. Results obtained in asymmetric catalysis, using chiral phosphine ligands, are therefore not directly transferable to the respective NHC-analogues. 

Oxygen only Nitrogen only AH other types of heterocyde... 

The (n,n ) excited state of a ketone has electrophilic character, similar to that associated with alkoxy radicals, and it is not surprising that these excited states readily attack carbon-carbon multiple bonds. The overall reaction that normally ensues is a cycloaddition, giving a tour-membered oxygen heterocyde—an oxetane from an alkene addend (4.62), or an oxete from an alkyne addend (4.63). Some oxetanes are of interest in their own right, but many are useful intermediates in the synthesis of other compounds. 

Silver(I)-catalyzed cyclizations of substituted allenes to heterocydic ring systems induding 2,5-dihydropyrroles have been described previously [4,10]. Moreover, sil-ver(I) salts are known to form stable rr-complexes with terminal acetylenes [11]. On the other hand, on treatment with silver nitrate silylacetylenes were reported to afford silver acetylides [12]. Based on these considerations and additional experimental evidence [5,13], the following mechanism has been proposed forthe sUver(I)-mediated oxidative cydization of homopropargylamines to pyrroles ]5] (Scheme 15.3). 

Wood, A. W., Chang, R. L., Kumar, S., Shirai, N., Jerina, D. M., Lehr, R. E and Conney, A. H. (1986), Bacterial and Mammalian Cell Mutagenicity of Four Optically Active Bay-Region 3,4-Diol-l,2-epoxides and Other Derivatives of the Nitrogen Heterocyde Dibenztc,h]acridine. Cancer Res, 46 2760-2766. 

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