Cyclization heterocycles from

It is known that 1,2,4-triazine 4-oxides, in contrast to 1,2,4-triazine 1- and 2-oxides, cannot be obtained by oxidation. Therefore, the only way to obtain 1,2,4-triazine containing the A -oxide group at position 4 of the heterocycle is to form the tiiazine ring by cyclization, starting from compounds bearing nitroso (isonitroso) or hydroxylamino groups. There are several ways to carry out such cyclizations. 

A useful route to 2,1,3-benzothiadiazoles is the F -catalyzed cyclization of l-(4-X-C6F4)-3-trimethylsilyl-l, 3-diaza-2-thiallenes [90JFC(50)359]. Fluoride ion catalysis is also used in the formation of heterocycles from pentafluorobenzoyl and -phenoxy compounds (81BCJ3447). Pentafluoro-phenylcarbonimidoyl dichloride with primary amines gave guanidines,... 

Cyclization arising from the intramolecular photoelimination of HC1, HBr, and HI has been extensively used in the synthesis of heterocycles and alkaloids. The mechanisms of these transformations have not in many cases been thoroughly investigated. Some undoubtedly are initiated by simple homolysis of the carbon-halogen bond whereas others involve photocycliza-tion and subsequent elimination of HX. 

Electrosyntheses of heterocycles from nitroso derivatives prepared in a batch cell according to Scheme 34 need two conditions. The first one is a good stability of the hydroxylamine intermediate and the second one is a very fast cyclization of the nitroso compound to avoid the formation of an azoxy compound by condensation of the generated nitroso and the hydroxylamine. Electroanalytical studies using cyclic voltammetry can give information on the rate of cyclization. 

Asymmetric synthesis of heterocycles from olefins via cyclization with the formation of carbon-heteroatom bonds 84MI1. 

Various bicyclic heterocyclic compounds have been prepared by cyclization reactions from various aminopyrazines, and some of these preparations are listed in Table VIII.1. 

Pyridine hydrohalides as reagents in heterocyclization 77KGS579. o-Quinone diazides, formation of condensed heterocycles from 80MI49. Radical cyclization in synthesis of hcterocycles 84YGK1121. 

Enamides, cyclization of, with N-heterocycle formation 84YGK225. j -Haloenamides, synthesis of N-heterocycles from 830PP71. 

This reactivity of iV-acylenamines 1 has opened up new possibilities for the use of enamides.in photochemical rearrangements as weU as in acid-catalyzed cyclizations , which lead to a variety of complex nitrogen-containing heterocycles from readily available simple precursors. These reactions have also been used to form a wide variety of natural products and polyfunctional compounds. Enamides can be also used as electrophilic reagents for amidoalkylation -, which can occur under certain conditions as a [4 -I- 2] cycloaddition to form 1,3-oxazinium heterocycles... 

Syntheses of the heterocycle from 2-nitrobenzenethiol involving reductive cyclization methods have been employed by a number of research groups. 

The introductory comments on pp. 398-399 also apply to this chapter. The synthesis of heterocycles from 1,2-diamines has been reviewed [3562]. Other cyclizations in which 1,2-diamines take part are mentioned in Chapter II, Section 1.6, Chapter 30, Section II.4 and Chapter 81, Section II. 1. 

Scheme 15. Synthesis of Heterocycles from 1,6-Dienes, Enynes, and Diynes via (a) Cycloisomerization, (b) Tandem Addition—Cyclization, and (c) Cycloaddition...

Substitution of one of the ester groups for another functional group may also allow one mode of cyclization to occur. Where cyanide replaces one of the esters, cyclization occurs from the cyano-stabilized anion. Seven-membered (e.g. 60) and heterocyclic (e.g. 61) rings - can be prepared regio-selectively. In competition between an ester and the PhS02-stabilized anion the latter cyclizes even where it is secondary and the ester is primary, (62) to (63), presumably in part a reflection on the electro-philicity of the two groups and the stabilities of the products. The ester lactone (64) cyclizes to the keto ester (65) involving the enolate of the lactone, but cyclization in the opposite sense is sterically unlikely (Scheme 28). ... 

This cyclization also affords a route to nitrogen heterocycles from acyclic dienyl-amines and -amides. Pyrrolincs can be obtained from diallylamines. This reaction can also form tetrahydropyridines and -azepines, as well as lactams.3... 

Kim developed a new entry into A -heterocycles by radical cyclizations onto alkyl azides. Iodides, bromides and thionocarbonates (Scheme 28, Eq. 28.1) are suitable radical precursors. 5-Exo cyclizations afford 3,3-triazenyl radicals that lose N2 to furnish an aminyl radical [79]. Following this work, Kilburn has applied this strategy to the formation of spiro-heterocycles from methylenecyclopropanes [80]. Finally, this reaction was applied as a key step in a very elegant cascade synthesis of aspi-dospermidine developed by Murphy (Scheme 28, Eq. 28.2) [81]. 

This book is a volume in the series Topics in Heterocyclic Chemistry. It covers the key methods used for designing synthetic approaches to heterocycles from carbohydrates and the value and scope of these methods. Carbohydrates are widely distributed in nature and constitute the largest part of renewable biomasses. Moreover, many carbohydrates and their derivatives are commercially available at relatively cheap prices. Consequently their utiUzation is highly encouraged and economically they are of great significance. Moreover, carbohydrates are highly functionahzed compounds that can be readily deriva-tized and/or cyclized to provide heterocychc compounds. 

The relative ease of the cyclization step from A to C may also be linked to the nucleophilic or coordinative ability of the heteroatom bound to the metal. The reaction of 7 with diphenylacetylene (Ph2C2) leads to the seven-membered derivatives 68 and 69 after prior isolation of the monoinsertion product 24, treatment with a silver salt, followed by the usual thermolytic conditions. This is another rare example of an intramolecular formation of a C-S bond within the coordination sphere of a transition metal and a novel, albeit limited to one alkyne, route to the rare family of dibenzo[bd] thiepins. With the closely related 8, which differs from 7 only by the tertiary amine unit in the metallacyclic framework instead of a thioether function, a carbocyclic product 71 is obtained (see under carbocycle reactions, next section). The formation of the seven-membered S-heterocycles is attributed to the good coordinative ability of the thioether group in 7. The S-atom remains close to the vinylic carbon function before the cyclization. With the poorly coordinating, readily displaced amine function in 8, the N-atom is detached from the metal and ultimately affords a spirocyclic product (see Scheme 18). 

The intramolecular trapping of benzyne intermediates with tethered nucleophiles is a powerful strategy for the synthesis of benzo-fused heterocycles. In this field, 7-functionalized benzoxazoles 59 and benzothiazoles 60 have been prepared by anionic cyclization of the corresponding lithiated benzyne (thio)amides and (thio)carbamates, which were generated from 3-haloaniline derivatives (Scheme 12.34) [55]. Related to this, substituted indolines 61 have also been accessed by benzyne-mediated cyclization-functionalization from Boc-protected (2-bromo-4-methoxy)phenetylamines using Mg(TMP)2 2LiCl as a base. This methodology has also been applied to the preparation of functionalized carbazoles (Scheme 12.34) [56]. 

The most studied and widespread type of fluorinated triazines are 1,3,5-triazines. As well as their isomer compounds, fluorinated 1,3,5-triazines can be synthesized by several ways (i) the formation of heterocyclic ring by means of cyclization reactions from fluorine-containing precursors (ii) direct fluorination of triazines (iii) nucleophilic displacement reactions of chlorinated triazines with the fluorine ion, and other synthetic procedures. 

The rapid development of C-H functionalization has helped in accomplishing the synthesis of a variety of complex heterocycles from simple precursors. Recendy, Ramana and co-worker demonstrated a simple one-pot procedure for the Cu(I)-catalyzed SNAr reaction of o-bromochalcones 1 with sodium azide followed by intramolecular cyclization through nitrene C-H insertion to provide 2-aroylindole derivatives 2 [56] (Scheme 7.1) on the basis of their previous work [57]. Furthermore, this methodology is also applicable with the 2 -bromocinnamates giving the indole-2-carboxylates. 

Oh and coworkers successively developed a series of highly efficient methods for the construction of various types of fused polycyclic heterocycles from enynals with a pendant unsaturated bond [72]. Enynals with a benzyloxy substituent at the propargylic position 155 were successfully cyclized via platinum-catalyzed Huisgen-type cycloaddition to form polycyclic Pt-carbene complex intermediate 156, which undergo insertion into a C-H bond to afford various types of fused polycyclic heterocycles 157 (Scheme 12.68) [73]. 

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