Four-membered heterocycles aromaticity

From an aromaticity-antiaromaticity point of view, an intriguing representative of the four-membered heterocycles is undoubtedly the hitherto unknown azete (21 R1=R2 = R3 = H). Theory... 

Tandem intermolecular Paterno-Biichi reaction of benzophenone with trimethylsilyl vinylcyclopropyl ether 72 (Scheme 31) leads in its first step to the formation of seven-membered 73 rather than to four-membered heterocycle while its second step proceeds in a normal fashion. With aromatic aldehydes, only tetrahydrooxepine derivatives 74 are formed <1998J(P1)2363>. 

The main thrust of this book concerns the aromatic heterocycles, exemplified above, however Chapter 30 explores briefly the chemistry of saturated or partially unsaturated systems, including three- and four-membered heterocycles. 

With this large group of heterocycles, ring strain is of little or no importance. Ring-opening reactions are, therefore, rarer than in three- and four-membered heterocycles. The crucial consideration is rather whether a compound can be regarded as a heteroarene or whether it has to be classified as a heterocycloalkane or heterocycloalkene (see p 2). Various aromaticity criteria apply to heteroarenes, and as a consequence, different opinions have been expressed on this matter [1]. As will be shown by means of examples of the various systems, the nature and number of heteroatoms are the critical factors. The parent compound of the five-membered heterocycles with one oxygen atom is furan. 

Onium ions of small and large heterocyclics are usually produced by electrophilic attack on a heteroatom. In three- and four-membered rings nucleophilic attack on an adjacent carbon follows immediately, in most cases, and ring opening stabilizes the molecule. In large rings the onium ion behaves as would its acyclic analog, except where aromaticity or transannular reactions come into play (each with its electronic and steric pre-conditions). A wide diversity of reactions is observed. 

Pyrrole (two r s, one /) and imidazole are /ive-membered heterocycles, yet both have six tt electrons and are aromatic. In pyrrole, each of the four. sp2-hybridized carbons contributes one tt electron, and the sp2-hybridized nitrogen atom contributes the two from its lone pair, which occupies a p orbital (Figure 15.9). Imidazole, also shown in Figure 15.9, is an analog of pyrrole that has two nitrogen atoms in a five-membered, unsaturated ring. Both nitrogens are sp2-hybridized, but one is in a double bond and contributes only one electron to the aromatic tt system, while the other is not in a double bond and contributes two from its lone pair. 

Diathiadiphosphetane disulfides are probably the most studied and the most thermally and hydrolytically stable of all the phosphorus-chalcogen heterocycles. They contain a central four membered P2S2 ring and can be prepared from heating phosphorus pentasulfide with aromatic compounds. The most well-known of these is Lawesson s reagent (43), which is made from anisole and phosphorus pentasulfide,92 and is used extensively in organic synthesis procedures (see Section 5.4.1). Other dithiadiphosphetane disulfides of note are 44 and 45, formed from the reaction of phosphorus pentasulfide with ferrocene or 1 -bromonaphthalene respectively.93... 

In five-membered heterocycles, formally derived from benzene by the replacement of a CH=CH unit by a heteroatom, aromaticity is achieved by sharing four p-electrons, one from each ring carbon, with two electrons from the heteroatom. Thus in pyrrole, where the heteroatom is N, all the ring atoms are sp hybridized, and one sp orbital on each is bonded to hydrogen. To complete the six 7i-electron system the non-hybridized p-orbital of N contributes two electrons (Box 1.9). It follows that the nitrogen atom of pyrrole no longer possesses a lone pair of electrons, and the compound cannot function as a base without losing its aromatic character. 

Thietes, four-membered precursors for the synthesis of 1,3-dilhianes or 1,3-oxathianes, provide access to the target heterocycles by reacting with either carbon disulfide and Lil <2002IJB1234, 2003S340> or, when the ring system denoted in Scheme 110 is aromatic, with diethyl 2-oxomalonate via a [4-1-2] cycloaddition pathway <1998JHC1505>. 

The reactions of dihydro compounds are of two main classes. The first class comprises reactions to regain aromaticity which depend intrinsically on the dihydro six-membered heterocyclic structure and these can in turn be subdivided into four groups, of which the first is by far the most important ... 

Isolated examples of oxidation at nitrogen have been reported for these systems. They do not form the N-oxides typical of aromatic nitrogen heterocycles, but behave similarly to amines. Thus the 1,2,5-oxadiazine (80) is rapidly oxidized by lead dioxide to the radical (81) (73JA1677), which is in equilibrium with the four-membered ring radical (82). 

A difficulty arises with five-membered heterocycles such as pyrrole, which at first sight would appear to have only four jc electrons, two short of the An + 2 Hiickel criteria for aromaticity. The nitrogen atom is sp2 hybridised and formally contains a lone pair of electrons in the remaining p orbital at right angles to the ring. However, the system is delocalised, as shown below. 

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