Five-membered Heterocyclic Unsaturated Compounds

Pyrrole is a nitrogen-containing unsaturated five-membered heterocyclic aromatic compound. It shows aromaticity by delocalization of a lone pair of... 

Five-Membered Unsaturated Heterocyclic Compounds The three well-known unsaturated five-membered heterocyclic compounds are furan, I, thiophene, II, and pyrrole, III, which may be considered as analogues of cyclopentadiene, TV. 

These compounds exhibit a very intense band below 220 mp due to the diene absorption and a low intensity band at longer wavelengths. The long wavelength band is most intense in the case of thiophene, possibly because of the interaction of the low-lying rf-orbitals. Some of the other unsaturated five-membered heterocycles for which the absorption spectra have been reported are imidazole, V, 1,2,3-triazole, VI, tetrazole, VII, and thiazole, VUI. The absorption data of the five-membered unsaturated heterocyclic compounds are summarized in Table 6.1. 

The 2 + 3 cycloaddition implies a reaction between 1, 3 dipole and an unsaturated compound called dipolarophile. The product of the reaction is a five membered heterocycle. Its theory has been develoed by R. Huisgen. According to him there are four classes of dipoles distinguished by then-bonds and the way they are stabilized by conjugation. 

Unsaturated and saturated compounds are considered in the same sections since the number of five-membered heterocycles with three and more heteroatoms (and especially their structure types) is limited and their reactivity does not differ fundamentally. 

Lactones are cyclic esters derived from lactic acid (CsHeOs). They are constituents of many essential oils and plant volatiles. They contain a heterocyclic oxygen next to a carbonyl function in a five or more membered ring that is saturated or unsaturated. Those with a five-membered ring are called y-lactones, e.g. y-angel-ica lactone 148, whereas compounds containing a six-membered ring are called (5-lactones, e.g. (5-valerolactone 149 (Structure 4.45) [1-4, 6, 9, 22, 23,29, 62]. 

Among the heterocyclic compounds, there are aromatic, e.g. pyridine, as well as nonaromatic, e.g. tetrahydrofuran, compounds. Similarly, there are saturated (e.g. tetrahydrofuran) and unsaturated (e.g. pyridine) heterocyclic compounds. Heterocycles also differ in their ring sizes, e.g. pyridine has a six-membered ring, whereas tetrahydrofuran is a five-membered oxygen-containing heterocyclic compound. 

Simple ring-opening reactions ([5 -> 5] isomerizations), which might be considered as the reversal of well-known cyclization reactions, are rather uncommon in five-membered ring compounds, and only few examples are known for unsaturated heterocycles such as pyrrole (8), dihydrofurans (9, 10), and isoxazoles (11). 

American practice is to use the terminations -ane for saturated and ene for unsaturated compounds in both the hydrocarbon and the heterocyclic series. British usage is essentially the same for hydrocarbons, but for heterocyclic molecules the final e is omitted in fact, a terminal e is used in general only for hydrocarbons, bases, and the five-membered ring ending ole. This leads in particular to some differences in the spelling of both trivial and systematic names for one-ring heterocycles e.g., thiophen, oxiren, dioxaphospholan (British) thiophene, oxirene, dioxaphospholane (American). 

The most general approach to synthesis of five-membered heterocyclic compounds involves cycloaddition of a 1,3-dipole to an appropriate unsaturated substrate, the dipolarophile. Intermolecular cycloadditions result in the formation of one new ring only. When the 1,3-dipole and the substrate are part of the same molecule, cycloaddition is intramolecular and leads to a new bicyclic system. Thus, intramolecular... 

Much work in the review period has concerned enantioselective substitution in five-membered heterocyclics. The enantioselective alkylation of some pyrroles by unsaturated 2-acylimidazoles catalysed by the bis(oxazolinyl)pyridine-scandium(in) triflate complex (31) has been reported.39 Compound (33) is formed in 98% yield and 94% ee from the 2-acylimidazole (32) and pyrrole at —40 °C. A series of enantiomer- ically pure aziridin-2-ylmethanols has been tested as catalysts in the alkylation of /V-mclhylpyrrolc and (V-methylindole by ,/l-unsalura(cd aldehydes.40 Enantiomeric excesses of up to 75% were observed for the alkylation of /V-mcthylpyrrole by ( >crotonaldehyde using (2.S ,3.S )-3-mclhylazirin-2-yl(diphenyl)methanol TFA salt as catalyst to form (34). 

Thus, the interaction of 6>r /z6>-diamines with unsaturated 1,4-diketones results in the formation of six- or five-membered heterocycles. This fact shows that the formation of these compounds is more advantageous from the viewpoint of thermodynamics in comparison with the formation of seven-membered dihydrodiazepine systems. 

We will take a semiempirical approach using numerous molecules, models, assumptions, and estimates rather than doing new calorimetric experiments and/or quantum chemical calculations. Indeed, we will also test what is probably the simplest assumption - that (4n + 2) n electrons found within a conjugated ring species is expected to result in enhanced stability and that this compound is called aromatic. We will consider the dihydroindene (indane) skeleton composed of a benzene ring fused to a nonaromatic five-membered ring that lacks additional double bonds, and will use this carbocyclic hydrocarbon with X = Y = Z = CH2 as a paradigm for many heterocyclic derivatives for which the possible aromaticity is of relevance to the current chapter. Similarly we use indene with -X-Y- = -CH=CH-, Z = CH2 for a variety of unsaturated heterocycles of interest here. 

A 1,3-dipole is a compound of the type a—Het—b that may undergo 1,3-dipolar cycloadditions with multiply bonded systems and can best be described with a zwitter-ionic all-octet Lewis structure ( Huisgen ylid ). An unsaturated system that undergoes 1,3-dipolar cycloadditions with 1,3-dipoles is called dipolarophile. Alkenes, alkynes, and their diverse hetero derivatives may react as dipolarophiles. Since there is a considerable variety of 1,3-dipoles—Table 12.2 shows a small selection—1,3-dipolar cycloadditions represent not only a general but also the most universal synthetic approach to five-membered heterocycles. 

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