Formation of Other Ring Systems

Formation of Other Ring Systems from Aziridines. The aziridines (262 R = Ph, 4-CIC6H4, or 4-MeC6H4) reacted with R NC (R - Pr Ph, Bu, or Bu CH2CMe2) in CH2CI2 to give the azetidines (263 R = phthalimido) (40— 49%). The azetidines subsequently yielded acyclic imines after rearrangement. 

An improved synthesis of the pyrrolidinones (265 R = Ph, 4-CIC6H4, 3,4-CI2C6H3, 1-naphthyl, or Et) from (264) involves their reaction with excess NaCH(C02Et)2 in the absence of solvent. 

Hanaoka, S. Yasuda, K. Nagami, K. Okajima, and T. Imanishi, Tetrahedron Lett., 1979, 3749. J. Charner, H. Person, and A. Foucaud, Tetrahedron Lett., 1979, 1381. 

The aziridine ring in (266) is stereospecifically cleaved in AcOH containing Et02CNHNH2, to produce the oxazolidinones (267) and (268).  

The iodide-catalysed ring-opening of (269 R = H) gave a quantitative yield of (270 = R = H). ° For (269 R = Me) the cyclization produced both (270  

or 3-NO2 R = H, 4-Br, or 4-Cl) with MeCN gave the BF3 adducts of the imidazolidines (287) (62-78%). With MeONa, (287) isomerized to the fra/is-imidazolidines. The same aziridines (286) were found to condense with acetone in the presence of Et3N to yield the oxazolidines (288) (55-80%). ° The reaction of (289 R = OEt, 4-CIC6H4NH, Ph, or Ph2N) with R CH(COOEt)2 (R = Ph or Me) afforded (290) via ring-opening and subsequent cyclization.  

The vinylaziridine (291) undergoes cycloaddition reactions with unsaturated substrates. With (292), at — 20 °C, the product is (293) (95%) with 

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The halogenated derivatives of six membered heterocycles, like their carbacyclic analogues, usually participate readily in coupling reactions that involve the incorporation of an olefin or carbon monoxide. The insertion of carbon monoxide commonly leads to the formation of either a carboxylic acid derivative or a ketone, depending on the nature of the other reactants present. Intermolecular and intramolecular variants of the insertion route are equally popular, and are frequently utilized in the functionalization of heterocycles or the formation of annelated ring systems. 

As mentioned in CHEC-II(1996), three main routes have been reported for the formation of furazan rings (1) the dehydrative cyclisation of 1,2-dioxims (2) the deoxygenation of furoxans and (3) the Boulton-Katritzky rearrangement of other five-membered heterocyclic systems <1996CHEC-II(4)229>. In this section the recent publications on the synthesis of furazans published after 1996 are discussed. 

The intramolecular cycloadditions of cychc nitronates have received much more attention. The cyclic nitronate structure provides three basic modes of intramolecular cycloaddition (Fig. 2.15). Attachment of the tether to the C(3) position of the nitronate results in the formation of a sprro system (sprro mode). However, if the tether is appended to the C(4) position of the nitronate, the dipolar cycloaddition yields a fused ring system (fused mode). Finally, if the tether is attached at any other point of the cyclic nitronate, the cycloadducts obtained will consist of bicyclic structures (bridged mode). 

As with the other procedures for the preparation of six-membered heterocyclic systems which proceed via formation of only one ring bond there are relatively few methods which involve formation of a ring bond y to the heteroatom and which can best be classified as [6 + 0] processes rather than [4 + 2], [3 + 3], etc, processes. Of those which can be so represented, however, a number are important processes which are widely used for the synthesis of saturated, partially saturated and aromatic six-membered heterocyclic systems and their benzo derivatives. Mechanistically, the nucleophile —> electrophile approach is by far the most common, but in contrast to the reactions discussed in the previous three sections, radical cyclizations are of considerable utility here. 

These reviews often contain tables of compounds together with the routes used to prepare them and in many cases reference in the present work will be directly to the appropriate chapter. Nevertheless, there are in most cases direct references to all the principal routes of synthesis in such a restricted format a completely comprehensive account is impossible. The section on synthesis from other ring systems is weighted towards the work of the last 20 years. 

If the numbering of a ring system is not already fixed, a radical position normally takes precedence over all others, except a position carrying indicated hydrogen, for lowest number. However, when the indicated hydrogen is cited only as a result of formation of a bivalent radical, this order is reversed (e.g., 187). 

Methods of heterocyclic synthesis can be divided into two main types those in which the ring system is built up from aliphatic components and those in which derivatives of other heterocyclic systems are used as starting materials. The essential step in most pyrazine syntheses from aliphatic components is C-N bond formation and various schemes for the synthesis of the required C4N2 ring system are illustrated below. The primary product is in many cases a reduced... 

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