Five-membered heterocycles, ring transformations

Ferrocenes, heterocyclic, 13, I Five-membered heteroaromatic anions, ringopening of, 41, 41 Five-membered heterocycles, ring transformations of. 56, 49 Five-membered ring fluoro-heterocycles, 60, I... 

In the first chapter, D. S. Donald and O. W. Webster summarize much fundamental heterocyclic chemistry dealing with the preparation of heterocycles from hydrogen cyanide and its derivatives, mostly previously available only in the patent literature. In the second, the account of the ringopening of five-membered heteroaromatic anions by T. L. Gilchrist brings together the numerous transformations that can succeed the removal of a proton from a carbon atom in a five-membered heterocyclic ring. 

Preparations of cinnolines by expansion of five-membered heterocycle rings include the oxidation of A-aminooxindoles 232 (Scheme 132) <1988JHC847>, the treatment of isatogens 233 with ammonia (Scheme 133), and the base-catalyzed conversion of 1-aminodioxindoles 234 into cinnolin-3-ones 235 (Scheme 134) <1960JA4634>. Additional examples of the synthesis of cinnolines by transformation of another ring are available in CHEC-III . 

Professor Nicolb Vivona and his colleagues from Palermo, Italy, have provided an overview of the present state of ring transformations of five-membered heterocycles which brings up-to-date a previous account by the same group published nearly 20 years ago in Volume 29 of these Advances. 

For reviews on ring transformation of five-membered heterocycles, see <93AHC(56)49> and CHEC-I <84CHEC-I(5)718>. 

The syntheses of five-membered heterocycles containing three oxygen or sulfur atoms in the 1,2,3-positions can be classified into three groups (i) one-component syntheses, in which a suitable acyclic molecule is cyclized by linkage of two heteroatoms (ii) two-component syntheses, in which the ring is built up either by a [3 -f 2] process or a [4 -1-1] process and (iii) synthesis by transformation of another heterocyclic ring. 

The types of Si-containing five-membered heterocycles synthesized heretofore are shown in Figure 1. Only a few of them were known prior to 1980. Bora rings (l,m) deserve mention as the subject of a very broad and comprehensive study which revealed a series of peculiar transformations and structures. Rings with the internal dative bonds (e.g. k, bb (X = F)) add another dimension to ring... 

Some of the ring expansion reactions discussed in Section 2.03.3.3.1 can be extended to five-membered heterocycles containing two or more heteroatoms. Reaction of imidazoles and pyrazoles with dichlorocarbene, for example, gives chloropyrimidines together with small amounts of chloro-pyrazines or -pyridazines, and oxidative ring expansion of 1-aminopyrazole with nickel peroxide gives 1,2,3-triazine (this, in fact, constitutes the only known synthesis of the unsubstituted triazine). There are, however, a number of interesting and useful transformations which are unique to five-membered polyheteroatom systems. 

A significant part of the examples of transition metal catalyzed formation of five membered heterocycles utilizes a carbon-heteroatom bond forming reaction as the concluding step. The palladium or copper promoted addition of amines or alcohols onto unsaturated bonds (acetylene, olefin, allene or allyl moieties) is a prime example. This chapter summarises all those catalytic transformations, where the five membered ring is formed in the intramolecular connection of a carbon atom and a heteroatom, except for annulation reactions, involving the formation of a carbon-heteroatom bond, which are discussed in Chapter 3.4. 

The introduction of nucleophiles onto five membered heterocycles through non-catalyzed aromatic nucleophilic substitution is of little synthetic value, since the comparatively high electron density of the aromatic ring makes the nucleophilic attack unfavourable. The introduction of transition metal catalyzed carbon-heteroatom bond forming reactions overcame this difficulty and led to a rapid increase in the number of such transformations. 

In the discussion of structural and spectroscopic aspects of thiophenes to follow, the reader does well to bear in mind that in fact aromaticity is a hallmark of thiophenes that dominates their properties and governs their reactions. Moreover, thiophene stands as uniquely aromatic among the five-membered heterocycles. In concrete terms this means that not only does thiophene undergo the reactions and have the physical and spectral properties associated with the concept of aromaticity, but that this aromatic character is steadfastly maintained through all manners of transformations including fusion with other aromatic rings. This attachment of substituents or fusion with other rings spawns thousands of aromatic derivatives. 

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