Rings — Transannular Effects

As soon as we progress beyond cyclohexane, we return to the more typical model of car-bocycles. Several conformers are close in energy, and they often interconvert over relatively small barriers. The situation rapidly becomes very complicated and a domain primarily for the aficionado of conformational analysis. Here we describe a few general features of these systems. 

Strain Energies and Group Increment Correction Factors for Cycloalkanes, (CH2 (in kcal/mol) 

The cis ring fusion must involve one axial and one equatorial C-C bond. This requirement has several important consequences. First, ds-decalin is less stable than fra/is-decalin by about 3 kcal / mol. Second, the cis form is flexible, as the axial and equatorial linkages can interconvert by a chair flipping process. 

The third key difference between cis- and trans-decalin relates to shape. The trans form retains and extends the relatively flat, disk shajje of chair cyclohexane, but the cis form forces a kink into the system. Fused cyclohexanes are common in biological structures, and because molecular shape is always crucial in biological recognition proces.ses, the cis vs. trans ring fusion issue is quite important. 

Most steroids, such as cholesterol, have all trans fusions or have olefins at a fusion (as in cholesterol or testosterone) or aromatic rings (as in estrone). Either way, the flat, fra/js-decalin shape is maintained, making these generally lipophilic molecules adopt an elongated, disk-like structure. A major role of cholesterol is to insert into and thereby stabilize cell membranes, and no doubt the molecular shape is crucial to this function. There are exceptions, such as cholic acid (a component of bile) which adopts one cis ring fusion. This cis ring fusion alters the molecular shape considerably, and also creates an interesting juxtaposition of the three hydroxyls. 

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For larger rings, 8c and 8d, the differences in chemical shifts of jp-carbons are about 1 p.p.m. The larger deshielding of the jp-carbons of 8b can be explained in terms of the diamagnetic anisotropy effect of the transannularly positioned diacetylene group, which was estimated by Roberts and coworkers , in addition to the ring strain effect. 

Another possible route for the development of total synthesis is the use of suitably selected monocyclic precursors with rings of medium size (20) the synthesis of which has been fairly well developed in recent years. Compounds of type (20) may subsequently be converted into polycyclic products (21) by using transannular effects. In this connection it must be mentioned that modern methods of total synthesis use ring closure by the formation of the internal bonds C5-C10, C3-C9, and C13-C14 shown in formula (21) by heavy lines only in isolated cases (Schemes 26 and 78). 

Depending upon substituents, transannular interactions in the [2.2]paracyclophane system are characterized by the steric or electronic effects of one aromatic nucleus on the physicochemical behavior of the other aromatic ring. The transannular reactions themselves, of course, are very dependent upon molecular geometry. 

This structiire may be compared with those of the recently reported isoelectronic carbon analogues RC(NSH)2CR(13, R=Me2N,Ph). In the carbon compounds the effect of the exocyclic substituent on ring conformation is remarkable. Thus the phenyl derivative is completely planar and has structural parameters consistent with a 10 TT-electron system while the dimethylamino derivative has a folded structiire with a transannular S-S distance of 2.I38 (Figure 3). 

The formation of the inter-ring S-S bond probably has the effect of converting two weakly anti-bonding (ir ) electrons to an S-S 0-bonding electron pair (cf. formation of transannular S-S bonds... 

Racemic argemonine (5) has been synthesized from the readily available tetrahydro-6,12-methanodibenz[c,/Iazocine (74) (120-122) through a sequence involving a Stevens rearrangement and in an overall yield of 53% from 74 (Scheme 11) (123). Hofmann degradation of 74 furnished the cxo-methylene compound 75 (120,122). An oxidative ring expansion of 75 afforded ketone 76, which was then reduced to secondary alcohol 77. A transannular reaction, effected by acetic acid-acetic anhydride, resulted in the formation of the tetra-... 

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