Bridged-bicyclic structures

Heterocyclization of a-mercapto acids with (azolylimino)indolones 182 (Scheme 36) afforded the spirocyclic thiadiazepinones 183 <1989IJB639, 1994PS27>. gem-Dithiol addition to bis(methylene)-substituted diketopiper-azine 168 afforded the bridged bicyclic structure 169 featuring two dithiazepane rings (Scheme 33) <1981JHC1545>. 

The product from the green Claisen reaction is, on the other hand, a fused rather than a bridged bicyclic structure, It can easily form a stable enolate anion. 

In a similar style, epoxidation of the two alkenes is totally stereoselective, occurring exo in nor-born ene and endo when methyl groups are present on the bridge. These stereoselectivities would be remarkable in a simple monocyclic compound, but in a rigid bridged bicyclic structure they are almost to be expected. 

This chemistry is quite different from the examples we have just seen. The starting material has a bridged bicyclic structure and was made by a Diels-Alder reaction (Chapter 35). Fragmentation is... 

The cycloadditions of diethyl diazenedicarboxylate and 3//-1,2,4-triazole-3,5(47/)-diones to 1,3-dienes where one only double bond is part of a fused or bridged bicyclic structure occurs with complete diastcrcoselectivity, since the diazene approaches the diene from the least hindered side, e.g., formation of 22 and 33. 

Dienic, trienic, and tetraenic propellanes (tricyclic compounds with a common C —C single bond) are relatively novel compounds that have been used as models for stereochemical studies. Propellanes with fused cyclohexadienc and three- or four-membered rings are in equilibrium with annulenes which have a bridged bicyclic structure. The stability of the annulene ring increases with increasing size2. 

In conclusion, the picrotoxinin binding site can accept a variety of compounds such as cyclodiene insecticides, y-BHC, toxaphene, bicyclic phosphates, and picrotoxinin (4). While the mode of interaction seems to be somewhat flexible, there appears to be a minimum requirement for active compounds to possess at least two of the three essential sites, i.e. two electronegative and one steric bulkiness (or hydrophobicity) sites within a definite range of distance. Bridged bicyclic structures are suited for the preparation of compounds which satisfy such structural requirements. 

In the next example, there are three possible sites for enolate anion formation, but only one product is formed and in good yield too. If we consider all three possible enolate anions, the choice is more easily made. First, the reaction that does happen. An enolate anion is formed from the ketone at the green site and acylation at carbon follows. The product is a fused rather than a bridged bicyclic structure and can easily form a stable enolate anion. 

This chemistry is quite different from the examples we have just seen. The starting material has a bridged bicyclic structure and was made by a Diels—Alder reaction. Fragmentation is initiated by formic acid (HCO2H), which protonates the tertiary alcohol and creates a tertiary carbocation. The ether provides the push. More serious electronic interactions are needed in this fragmentation as the C—C bond being broken is not in a strained ring. 

Scheme 16.26 Bridged bicyclic structures via r2.31-shift of fused hicyclic oxonium ylides.

Recently, Zhang et al. applied RuAAC reaction to synthesize a 1,5-triazole bridged bicyclic structure as a mimic of the CDE-ring of vancomycin (Fig. 1 Id), which is a highly important glycopeptide antibiotic for treating bacterial infections... 

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