Bridged bicyclic molecules

The traditional descriptors cisitrans, exojendo and syn/anti are unambiguous for some important and simple types of molecules. However, their range of application is limited. The first descriptors, cis lrans, should be used according to the IUPAC rules. For bridged bicyclic molecules, the following convention8 with respect to endolexo and synjanti should be followed (see Table 9). 

The molecular structures of a-, p, and y-chlordene (components of technical chlor-dane) have been determined from C1 n.q.r. and other spectral data. The C1 n.q.r. frequencies of a variety of pairs of cis- and trans-isomers of chloroethylenes (including the incorporation of this structural unit into bridged bicyclic molecules) indicate that cis-substituents produce measurably greater shifts than do trans-substituents. ... 

Reactions of NBD follow the pattern typically observed in bridged bicyclic molecules, namely, that reactions occur preferentially on the more accessible exo face, although there are a few exceptions which yield exclusively the endo products. The different modes of cycloaddition which are designated as [2 + n], are summarized following, and some representative examples are shown in Scheme 1. 

It was noticed in 1924 by the German chemist Julius Bredt (1855-1937) that one structural type was conspicuously absent among the myriad compounds isolated from sources in Nature. There seemed to be no double bonds attached to the bridgehead position in what are called bridged bicyclic molecules. The bridgehead position is the point at which the bridges meet (Fig. 3.44). Apparently, great... 

FIGURE 3.45 Three views of a bridged bicyclic molecule containing a double bond at the bridgehead. 

This relatively easy idea has more complicated implications. For example, the need to maintain planarity (pip overlap) in a Jt bond leads to the difficulty of accommodating a trans double bond in a small ring, or at the bridgehead position of bridged bicyclic molecules. In each case, the geometry of the molecule results in a twisted (poorly overlapping) pair oip orbitals. 

Now imagine two rings sharing three carbons in a bridged bicyclic molecule. Two cyclopentanes, for example, can share two or three carbons. We have seen the first case before (Fig. 5.50) and the second is drawn in Figure 5.56. In each case, the carbons at the fusion points are called the bridgehead positions (p. 121). 

Bridged (Section 5.7) In a bridged bicyclic molecule, two rings share more than two atoms. 

Bicyclic molecules are found in many natural product structures. Cocaine is a derivative of bicyclo[3.2.1]octane in which nitrogen replaces the carbon at the one-carbon bridge. 

Because the bridge holds the molecule in a fixed conformation, the cleaved diacid has to have a specific stereochemistry. There is no change at the stereogenic centres, so the reaction must give retention of configuration. We can confidently write the structure of camphoric acid with ris-CC H groups, but any doubt is dispelled by the ability of camphoric acid to form a bridged bicyclic anhydride. 

Now the newly formed enamine 117 can be alkylated by the allylic bromide in the side chain. To do this reaction, the molecule must put the side chain in an axial position 118. The resulting iminium salt 119 is hydrolysed on work-up to the bridged bicyclic product 114. 

As a notable exception, the bridged bicyclic l,2,4-trioxan-5-ones (37), obtained by the addition of a molecule of singlet oxygen to the 2/7-pyran-2-ones (36), are indeed unstable. At 25 °C they undergo decarboxylation to the enediones (39) with emission of light of low intensity (Scheme 1) <79JA5692>. No evidence for the 1,4-dioxins (38) is found. 

Samarium(II) iodide-promoted radical cydizations have also played a key role in the total synthesis of (-)-grayanotoxin III [43b]. Among the methods utilized for the synthesis of this molecule was an intramolecular ketyl olefin coupling reaction generating a bridged bicyclic ring system (Eq. 68). 

FIGURE 5.59 More of the naming protocol for bridged bicyclic compounds. This molecule is 3,3-dimethylbicyclo[3.2.1 ]octane. The red dots show the bridgehead atoms. These are not counted in sizing the bridges, but are counted in numbering the compound. 

Bridgehead position (Section 3.7) The bridgehead positions are shared by the rings in a bicyclic molecule. In a bicyclic molecule, the three bridges emanate from the bridgehead positions. 

As Stockhausen [264] has shown with analogous examples, in the hydroformylation of such bicyclic molecules containing a methylene bridge, the formyl group is added only in the exo-position. Thus, structures (e) and (f) are eliminated and the number of expected isomers is reduced to four. 

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