10.21 Product Class 21: Five–Five-Fused Hetarenes with One Heteroatom in Each Ring

S. P. Stanforth

General Introduction

Five–five-fused hetarenes with one heteroatom in each ring are conveniently categorized into four classes of hetaryl[n,m-p]hetarenes 2–5, which recognizes their isoelectronic relationship to the pentalene dianion 1 (▶ Scheme 1). This method of classification is adopted in three previous reviews covering this class of heterocyclic compounds.[1–3] In these reviews, the description of heterocycles as n,m-diheteropentalenes is used and this nomenclature is commonly encountered in the literature. In this chapter, the five–five-fused hetarenes will be described as hetaryl[n,m-p]hetarenes because this is consistent with the nomenclature used throughout Science of Synthesis. The relationship between these two systems of nomenclature is shown in ▶ Scheme 1. Note that in the case of the heterocycles represented by the general structure 3, these structures are either [2,3-c]- or [3,4-b]-fused systems depending upon the nature of the heteroatoms X and Z (see ▶ Scheme 2). The hetaryl[n,m-p]hetarenes 2–4 can all be represented as covalent structures whereas the hetaryl[3,4-c]hetarene system can be depicted by either the 1,3-dipolar structure 5 or an alternative “non-classical”covalent representation when at least one of the component heteroatoms, for currently known systems, comprises sulfur, selenium, or tellurium. Both representations are found in the literature. The hetaryl[3,4-c]hetarene system 5 is associated with a highest occupied molecular orbital that is similar in topology and energy to a nonbonding molecular orbital.[4] This feature distinguishes the hetaryl[3,4-c]hetarenes 5 from the other heterocycles 2–4. Substitution of the carbanion centers in structures 1A–1C with heteroatoms (and their associated lone pair of electrons) leads to the covalent hetaryl[n,m-p]hetarenes structures 2–4, respectively. In contrast, when substituting an alkenyl carbon atom in structure 1B with a heteroatom, the structure 5 is produced.

Scheme 1 Hetaryl[n,m-p]hetarenes and the Pentalene Dianion

There are 21 possible hetaryl[n,m-p]hetarene structures associated with each of the general formulae 2, 4, and 5 and 36 possible structures associated with the general formula 3 when the heteroatoms X and Z are chosen from oxygen, sulfur, selenium, tellurium, nitrogen, and phosphorus. This gives a total of 99 potential hetaryl[n,m-p]hetarene systems. Many of these systems are as yet unknown. Hetaryl[n,m-p]hetarenes that comprise either a tellurophene or phosphole ring fused to any other five-membered ring are relatively rare. In contrast, there is extensive literature relating to heterocycles comprising two fused thiophene rings, partly as a consequence of interest in these systems as polythiophene analogues in materials chemistry. Hetaryl[n,m-p]hetarenes that possess a pyrrole ring fused to another ring have attracted interest as indole analogues.

The IUPAC nomenclature of the hetaryl[n,m-p]hetarenes is derived from a fusion of the names of the two constituent five-membered heterocyclic rings, i.e. furan, thiophene, selenophene, tellurophene, pyrrole, and phosphole. This is illustrated in ▶ Scheme 2 for the thiophene–pyrrole ring fusion modes. Note that the hetaryl[2,3-c]hetarenes/hetaryl[3,4-b]hetarenes are unsymmetrical and two possible isomers can exist: for example, 5H-thieno[2,3-c]pyrrole and 1H-thieno[3,4-b]pyrrole. In the old literature, the thienothiophenes 2, 3, and 4 (X = Z = S) are collectively named “thiophthens”but this terminology is not found in the modern literature. Similarly, the name “selenophthen”was used in the past for selenophenoselenophenes. For hetaryl[n,m-p]hetarenes possessing a selenium-containing ring, both the constructions selenopheno[n,m-p]hetarene and selenolo[n,m-p]hetarene (preferred) are encountered in the literature. There are several related methods for naming the hetaryl[3,4-c]hetarene ring systems that are found in the literature, all of which include the basic stem for naming the two fused rings. This is illustrated for the hetaryl[3,4-c]hetarene system 5 (X = Z = S), derivatives of which have been named as thieno[3,4-c]thiophenes, SIV-thieno[3,4-c]thiophenes (to take into account the nonstandard valence state of the sulfur atom), or more recently as 2λ4δ2-thieno[3,4-c]thiophenes. The hetaryl[3,4-c]hetarenes 5 are members of a class of heterocyclic molecules described as “heteropentalene mesomeric betaines”or “non-classical heteropentalenes”, a categorization which reflects their 1,3-dipolar nature.[4]

Scheme 2 IUPAC Nomenclature of Hetaryl[n,m-p]hetarenes as Represented by the Thiophene–Pyrrole Fusion Modes

The five–five-fused hetarenes with one heteroatom in each ring have not been previously reviewed in Houben–Weyl. A preliminary review in 1984[1] and two subsequent updates from 1996[2] and 2006[3] detailing aspects of the synthesis, chemistry, and physical properties of hetaryl[n,m-p]hetarenes have appeared. Two substantial reviews from 1976 and 2006 covering the preparation and chemistry of the various thienothiophene ring systems have also been published.[5,6] Azapentalenes (i.e., heterocyclic systems in which one or more of the carbon atoms in the pentalene dianion 1 are replaced with nitrogen) have also been reviewed.[7] Heteropentalene mesomeric betaines, of which the hetaryl[3,4-c]hetarene system 5 is a representative structure, have been reviewed.[4]

As a consequence of their isoelectronic relationship with the pentalene dianion 1, the hetaryl[n,m-p]hetarenes 2–5 exhibit aromatic character because they are associated with 10 p-electrons. The chemistry of these bicyclic systems reflects this aromatic character and the reactivity profile of their constituent five-membered rings. Thus, electrophilic substitution and C— H metalation reactions are well-known and these processes are described in appropriate sections of this review. These reactions allow the synthesis of hetaryl[n,m-p]hetarenes by substituent modification. One class of reaction that differentiates between the various hetaryl[n,m-p]hetarene systems are cycloaddition reactions. Numerous cycloaddition reactions of the hetaryl[2,3-c]hetarene, hetaryl[3,4-b]hetarene, and hetaryl[3,4-c]hetarene systems have been reported and representative examples can be found in the review articles.[1–4] In contrast, the cycloaddition chemistry of other hetaryl[n,m-p]hetarene systems is comparatively rare; some examples of the reactions of furo[3,2-b]pyrroles with electron-deficient alkynes are known and these have been reviewed.[2] It is noteworthy that although several examples of the parent hetaryl[n,m-p]-hetarenes 2–4 have been isolated and characterized, this is not the case for the parent hetaryl[3,4-c]hetarenes 5, which are too reactive to enable isolation.

Experimental structural methods that can be used in the characterization of hetaryl[n,m-p]hetarenes have been reviewed in depth.[1–6] The methods discussed include NMR spectroscopy (1H, 13C, 15N, 77Se), UV spectroscopy, IR spectroscopy, mass spectrometry, photoelectron spectrometry, electron paramagnetic resonance, dipole moments, polarography, and X-ray diffraction studies. The melting points of several of the parent hetaryl[n,m-p]hetarene systems have also been tabulated.[2] Also included in the review articles are theoretical studies of the hetaryl[n,m-p]hetarenes, which generally support the categorization of these molecules as electron-rich aromatic heterocycles. The role of sulfur 3d orbital participation in the hetaryl[3,4-c]hetarenes 5 (X or Z = S) has been debated.
Brief mention should also be made of hetaryl[n,m-p]hetarene derivatives that are isoelectronic with pentalene 6. Such heterocycles are therefore associated with 8 p-electrons and are formally antiaromatic. Examples of this class of heterocycle (▶ Scheme 3) include the stable pyrrolo[3,4-c]pyrrole (2,5-diazapentalene) derivative 7[8] and the pyrrolo[3,2-b]pyrrole (1,4-diazapentalene) derivative 8, which is reported to be unstable in air at room temperature.[9]

Scheme 3 Pentalene and Antiaromatic Pyrrolopyrrole Derivatives[8,9]

In order to maintain consistency in the depiction of the...