Five- and Seven-membered Ring Systems

Substituent effects (electronegativity, configuration) influence these coupling constants in four-, five- and seven-membered ring systems, sometimes reversing the cis-tmns relationship so that other NMR methods of structure elucidation, e.g. NOE difference spectra (see Section 2.3.5), are needed to provide conclusive results. However, the coupling constants of vicinal protons in cyclohexane and its heterocyclic analogues (pyranoses, piperidines) and also in alkenes (Table 2.10) are particularly informative. 

The table shows that E2 eliminations, particularly in five- and seven-membered ring systems, are not completely stereospecific, but four- and six-membered rings exhibit strong preferences. Six-membered rings in particular show distinct anti selectivity, because it is very easy for such systems to reach the rrans-diaxial conformation (12) (Scheme 11 Barton s rule). This anti selectivity can be seen very clearly in the elimination reaction with the isomers of 1,2,3,4,5,6-hexachlorocyclohexane. The isomer (13), which has no Cl trans to an H, loses HCl about 7000 times more slowly than the slowest of the other isomers. ... 

As we accounted for the difficulties mentioned in ring-closures of fluorene derivatives (125) to fluoranthenes, the combinations of five- and six-membered carbon ring systems in a planar arrangement are associated with considerable angle strain. This obstacle should be cancelled out essentially in combinations of five- and seven-membered ring systems. The condensation products (170) and (172) of acenaphthenone and fluorene with (44) in the following examples indeed cyclize under relatively smooth conditions by formation of such systems47. ... 

Figure 3.15. The basics of the model of a defective graphene layer (non-planar) showing vacancies, and five- and seven-membered ring systems (adapted from O Malley et al., 1998).

The possible variations among the three atoms comprising this reactive component make this the largest group and the one with the most potential for further development. They are particularly useful in the synthesis of five-, six- and seven-membered ring systems. They also may be conveniently considered according to their atom composition, and the hybridization state of any carbon atoms involved. 

Dipolarophiles utilized in these cycloadditions leading to five-membered heterocycles contain either double or triple bonds between two carbon atoms, a carbon atom and a heteroatom, or two heteroatoms. These are shown in Scheme 9 listed in approximate order of decreasing activity from left to right. Small rings containing a double bond (either C=C or C=N) are also effective dipolarophiles, but these result in six- and seven-membered ring systems. 

Wender et al. intensively studied the intramolecular Rh(I)-catalyzed [5+ 2] cydo-addition of allenes and vinylcydopropanes to yield fused systems of five- and seven-membered rings [151]. A typical example is the reaction of the enantiomerically... 

Intramolecular acylation of thiophenes has been thoroughly examined and shown to provide a reasonable route to substituted cycloalkanones on desulfurization of the bicyclic products (53BSF62, 73BSF343). A variety of five-, six- and seven-membered ring systems have been constructed, e.g. (285) — (287). 

The biological activity displayed by the perhydroazulenes, ranging from diuretic and anti-inflammatory to antitumor, combined with the unique bicyclo [6-3-0] system make them very attractive synthetic targets. The approach of Trost and Higushi to this class of compounds, exemplified by the total synthesis of isoclavu-kerin 65 (Scheme 12.12) [34], has the distinctive feature that it allows the simultaneous formation of both the five- and seven-membered rings through a palladium-catalyzed formal [3+2] cyclization as its key step [35]. 

Besides the common oleftnic dipolarophiles, other unsaturated systems have been evaluated in cycloaddition reactions of zwitterionic TMM-Pd complexes, including polyenes and acetylenes. While acyclic electron-poor dienes generally gave mixtures of five- and seven-membered rings [48], a limited number of selective [3 + 4] and [3 + 6] cycloaddition reactions have been achieved with cyclic polyenic substrates as illustrated by formation of cycloadducts 41 and 42 from pyrone [49] and tropone [50], respectively (Scheme 16). On the other hand, activated alkynes have failed to produce the corresponding cyclopentene derivatives [51]. 

In the cyclic series imidoyl halides are reported only for five-, six-, and seven-membered ring systems. However, it was demonstrated recently that 2,2-dichloroaziridines, which are obtained by addition of dichloro-carbene to C=N double bond compounds, react as iminium chlorides. The synthetic methods for the cyclic imidoyl halides are similar to those used for the preparation of the linear species. Therefore, emphasis is focused on the reactions of cyclic imidoyl halides rather than on their synthesis. The organization of this chapter also differs from that of the previous chapters because it is based on ring size rather than on the difference attributable to substituents attached to the C=N double bond system. 

The Hiickel rule was extended onto polycyclic nonaltemant systems Defining Fand Sas numbers of five- and seven-membered rings in a fused system, the molecule is more stable when S = F and less stable for other cases. This rule was then demonstrated and proved by use of the topological theories of aromaticity. °... 

Initial reports on the cycHzation of secondary amines, amides, and carbamates were communicated by Buchwald et al. Interestingly, different phosphines were necessary to access five-, six-, and seven-membered ring systems in high yields (Scheme 13.90) [136]. 

Besides monocyclic heterocycles, armelated bicyclic ring systems are also used in pharmaceutical fields. For example, the tetrahydroimidazothiazole levamisole (Fig. 11,2) is used as anthelmintic and inununomodulator [27]. A compound known as talipexole (Fig. 11,3) consists of five- and seven-membered rings and is used as an antiparkinsonian agent [28]. 

---