Polycyclic ring systems

Polycyclic compounds are those that contain more than one ring. The lUPAC classifies polycyclic structures according to the minimum number of bond cleavages required to generate a noncyclic structure. The structure is bicyclic if two bond disconnections yield an open-chain structure, tricyclic if three, tetracyclic if four, and so on. Adamantane, a naturally occurring hydrocarbon found in petroleum, for example, is tricyclic because three bond cleavages are needed before an open-chain structure results. 

The correct number of rings may be determined by different sets of disconnections, and the final open-chain structure need not be the same for different sets. All that matters is finding the minimum number of disconnections. 

Geohopanoids, compounds based on the carbon skeleton shown for hopane, have been found in every geological sediment that has been examined for their presence, and rank among the most abundant natural products on Earth. It is fairly easy to see that hopane contains five rings. Verify that hopane is pentacyclic by applying the bond-disconnection rule. 

In addition to classifying polycyclic compounds according to the number of rings they contain, we also classify them with respect to the way in which the rings are joined. In a spiro compound, one atom is common to two rings. 

The simplest spiro alkane is spiro[2.2]pentane, a molecular model of which illustrates an interesting structural feature of spiro compounds. The two rings lie at right angles to each other. 

Organic molecnles in which one carbon atom is common to two rings are called spirocyclic componnds. The simplest spirocyclic hydrocarbon is spiropentane, a product of laboratory synthesis. More complicated spirocyclic hydrocarbons not only have been synthesized bnt also have been isolated from natnral sources. a-Alaskene, for example, occurs in the fragrant oil given off by the needles of the Alaskan yellow cedar one of its carbon atoms is common to both the six-membered ring and the five-membered ring. 

PROBLEM 3.11 Which of the following compounds are isomers of spiropentane  

PROBLEM 3.12 Use the bond-cleavage criterion to verify that bicyclobutane and I camphene are bicyclic. J 

PROBLEM 3.13 Write structural formulas for each of the following bicyclic hydrocarbons  

SAMPLE SOLUTION (a) The bicyclo[2.2.1]heptane ring system is one of the most frequently encountered bicyclic structural types. It contains seven carbon atoms, as indicated by the suffix -heptane. The bridging groups contain two, two, and one carbon, respectively. 

Among the most important of the bicyclic hydrocarbons are the two stereoisomeric bicyclo[4.4.0]decanes, called cis- and franx-decalin. The hydrogen snbstitnents at the ring junction positions are on the same side in cA-decalin and on opposite sides in trans-decalin. Both rings adopt the chair conformation in each stereoisomer. 

Beginning with cycloheptane, which has four conformations of similar energy, conformational analysis of cycloalkanes becomes more complicated. The same fundamental principles apply to medium and large rings as apply to smaller ones—but there are more atoms, more bonds, and more conformational possibilities. 

The largest known cycloalkane has a ring with 288 carbons. 

Cubane (C4H8) is the common name of the polycyclic hydrocarbon shown. As it name implies, its structure is that of a cube. How many rings are presenf in cubane according to the bond-disconnection rule  

The anomeric effect is solvent and substituent dependent and decreases in the following order Cl OAc OMe OH, as exemplified by the equilibrium concentrations of the a and (3 anomers of substituted D-glucose in various protic solvents at 25 

Due to a deformation of the cyclohexane ring, c/5 -hydrindane (the numbers in [ ] refer to carbon atoms between the bridgehead carbons) is only slightly less stable than the trans isomer ( 1 kcal/mol). 8-Methylhydrindane is of interest since it occurs as part structure of the C/D rings of steroids (as a trans fused ring system). Introduction of an angular CH3 group makes the cis isomer more stable than the trans because the cis isomer has fewer 1,3-diaxial interactions. 

The decalin structural feature is contained in steroids, many of which have useful biological activity. Decalin can exist in two isomeric forms depending on whether the rings are trans fused or cis fused, rrans-decalin is constrained to a rigid conformation, whereas cw-decalin is conformationally mobile. 

Problems involving the flexible conformations of cw-decalin are more easily solved with the following chair-chair conformations. The descriptors a and (3 denote that the substituent is below the molecular plane or above the molecular plane, irrespective of axial versus equatorial. 

Note that trans- and cw-decalin are stereoisomers and not conformational isomers cw-Decalin is less stable than rran -decalin by 2.7 kcal/mol. 

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Entries 5 to 7 show intramolecular reactions. Entry 5 is an example of formation of a polycyclic ring system. The product is a 3 1 mixture of (3 a methyl isomers at the new ring junction, and reflects a preference for TS A over TS B. 

A novel approach towards the construction of the morphine skeleton is demonstrated by the total synthesis of ( )-desoxycodeine-D. One of the key steps for this synthesis is the palladium-catalyzed intramolecular Heck reaction. Therefore, this synthetic strategy for the construction of the polycyclic ring systems has provided an efficient access to the complete pentacyclic skeleton of morphine <00TL915>. 

Scheme 1.15 Solid-phase synthesis of a polycyclic ring system employing a U-4CR. 1.4 STEREOSELECTIVE U-4CR...

Appendix for polycyclic ring systems with C-heteroatom bonds... 

Diazo-2-oxindole (21c) reacted with benzyne and dimethyl acetylene-dicarboxylate in dichloromethane at 41°C to give polycyclic ring systems of type 265 (73TL1417) (Scheme 78). The intermediate spiro adducts 264 could not be detected, but it is reasonable to suppose that the final products were obtained by [1,5]sigmatropic rearrangement of the carboxamido moiety. 

Piperazine fused polycyclic ring systems are unique in terms of structures and properties. Praziquantel 211 is the primary medication for human schistosomiasis, for which it is usually effective in a single dose treatment. As shown in Fig. 10, praziquantel consists of a ketopiperazine fused ring system. A co-crystal of praziquantel and glutathione-5-peroxidase of the helminth Schistosoma japonica was known [63]. Praziquantel binds in a channel joining the two xenobiotic substrate... 

Although many hydrocarbons exhibit fluorescence, often they are colourless and the fluorescence is only just into the blue, e.g. the linear terphenyl and quaterphenyl. Polycyclic ring systems such as terrylene and rubicene are used in analytical methods and OLEDs but a large number are ruled out of commercial use because of their potential to act as carcinogens. However, as mentioned in section 3.5.1.3, pery-lene is a useful fluorophore in a variety of outlets and pyrene is another polycyclic compound of interest. One derivative of pyrene (3.27) is a yellow-green fluorescent dye used in textile applications (Cl Solvent Green 7) and in analysis and sensors (see section 3.5.6.4). 

Rather surprisingly the only polycyclic ring system to have found significant commercial application in FBAs is pyrene. The triazinyl derivative (3.64), which is synthesised by a Friedel-Crafts reaction between pyrene and 2-chloro-4,6-dimethoxy-l,3,5-triazine, is an important brightener for polyester and cellulose acetate. 

When phosphaalkynes are exposed to bis- and tris(diazo) compounds, bis- or tris(l,2,4-diazaphosphol-5-yl) compounds are formed that may be further converted into a variety of novel heterocyclic systems. For example, bis- and tris[diazo(tri-methylsilyl)methyl]phosphanes 237 and 240 afforded bis- and tris(diazaphospho-lyl)phosphanes 238 and 241 after cycloaddition with terf-butylphosphaacetylene followed by a subsequent 1,5-silyl shift (Scheme 8.56) (300). Reaction with electrophilic halides at the Wsilyl functions allows the introduction of a heteroatom bridge between the diazaphosphole ring leading to polycyclic ring systems such as 239 and 242. 

Carbonyl ylides were first reported to undergo intramolecular 1,3-dipolar cycloaddition to C—C double bonds in 1980.121 New polycyclic ring systems containing a tetrahydrofuran are formed. Dipola-... 

Pyrido[ 1,2-a]py rimidines represent a simple bicyclic ring system that contains a nitrogen-bridgehead condensed pyrimidine moiety. Synthetic methods for these compounds can often be applied to the preparation of similar bi- and polycyclic ring systems (e.g., benzologs, N-analogs, five membered congeners, and so on) and their reactivities are sometimes similar to those of the above-mentioned derivatives. 

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