Containing fused-ring systems, conformation

This chapter will deal exclusively with three-membered rings containing the hetero atoms O, S and N, and fused to the steroid skeleton. Because of the conformational requirements in steroids, not all of the usual methods of synthesis of three-membered rings are applicable to the fused ring system. For the synthesis of steroids to which an aziridine, oxirane or thiirane is attached either in the side chain or at a ring position but not directly fused to the nucleus, the methods discussed in this chapter, as well as others, are applicable. 

In the synthesis of cyclohexene oxide from cyclohexene shown, this does implicate the less favourable diaxial conformer in the epoxide-forming step. Cyclohexene oxide contains a c/s-fused ring system, the only arrangement possible, since the three-membered ring is necessarily planar (see Section 3.5.2). 

Similarly, in a 1,3-dipolar cycloaddition of DMAD to the conformationally locked cyclic a-alkoxycarbonylnitrone (727), bicyclic ring systems, containing a nitrogen atom at the bridgehead position have been synthesized. A mechanistic interpretation of the origin of the fused pyrroles (729) includes the intermediate formation of the aziridine ring in (728) (Scheme 2.303) (820). 

The nomenclature used in this section differs from the strictly systematic rules used by Chemical Abstracts to index fused-ring azetidinones, but conforms more to that commonly found in the literature describing the /3-lactam antibiotics. A description of this naming system is given in the introduction (Section 5.12.1). Virtually all of the compounds discussed in this section contain a carboxyl group adjacent to the /3-lactam ring and conform to general structure (49). 

Conformationally constrained triazacyclopenta[c]penta-lenes 128 are unprecedented tricyclic scaffolds and share the structural complexity characteristic of alkaloid natural products, such as triquinanes ° (e.g., 129 and 130), in that both scaffolds are composed entirely of fused five-membered rings and contain quaternary carbon centers (Figure 16.12). The triaza tricyclic ring system represents a source of chemical diversity that may complement traditional classes of heterocyclic compounds as potential pharmaceutical agents. 

Several indium-mediated intramolecular carbonyl allylation reactions have been investigated, and it has been found that these reactions provide an easy access to a variety of cyclic compounds. The intramolecular cyclization of 49a-c mediated by indium in aqueous media proceeds smoothly to afford carbocyclic systems containing y-hydroxy-Q -methylene esters 50a-c, which either spontaneously or readily cyclize to give fused o -methylene-y-butyrolactones 51a-c (Scheme 52). The same cyclization of 49d is too slow to compete with the side-reaction, in which the bromide is substituted by a hydroxy group. The ring junction stereochemistry of fused lactones 51 has been found to be cis in all cases. Of the two possible transition states, the one leading to the m-fused compounds is preferred, because the chair-chair conformation is favored over the chair-boat conformation.209... 

Condensed heterocyclo[n,m-n, b, or cjquinazolines. 52, I Condensed 4-thiazolidinones, 49, I Condensed thiophene systems, tetra- and pentacyclic, 32, 127 Condensed 1,2,4-triazines I. Fused to heterocycles with three-, four-, and five-membered rings, 59, 39 Condensed l,2,4-triazolo[3,4-z) heterocycles, synthesis, 49, 277 Conformational equilibria in nitrogen-containing saturated six-membered rings, 36, I... 

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