Carbon bridgehead

Bredt s rule A double bond cannot be introduced at the bridgehead carbon of a bridged bicyclic or polocyclic system with small- or medium-sized rings. 

The bicyclic compound decahydronaphthalene, or bicyclo[4.4.0]decane, has two fused six-mem-bered rings. It exists in cis and trans forms (see Fig. 1.10), as determined by the configurations at the bridgehead carbon atoms. Both cis- and rran -decahydronaphthaiene can be constructed with two chair conformations. 

The symbols f and f correspond to total fraction of and hybridi2ed carbon, respectively, f represents the fraction of carbon in aromatic rings f , the fraction in carbonyls, b > 165 ppm the aromatic fraction that is protonated the aromatic fraction that is nonprotonated f, the phenoHc or phenohc ether carbon, 6 = 150-165 ppm f, the alkylated aromatic carbon, 6 = 135-150 ppm , the aromatic bridgehead carbon f represents the fraction of CH or CH2 aUphatic carbon f, the CH or nonprotonated aUphatic carbon and f, the aUphatic carbon bound to oxygen, b — 50-90 ppm. 

Furthermore highly strained compounds such as bicyclo[3.2.1]oct-l-ene 11, containing a double bond to a bridgehead carbon atom, have been prepared however this strained olefin could be identified only as its Diels-Alder product from subsequent reaction with an added diene." ... 

According to Bredt s rule such olefins of small ring size are unstable ordinary elimination reactions usually yield an isomeric olefin where a bridgehead carbon does not participate in the double bond. 

For the formation of the new double bond, the general rules for eliminations do apply. Following Bredt s rule, no double bond to a bridgehead carbon atom will be formed. If the elimination can lead to a conjugated system of unsaturated groups, this pathway will be favored. Otherwise the Hofmann rule will be followed, which favors an elimination towards the less substituted carbon center. 

Figure 4.17 Representations of cis- and frans-decalin. The red hydrogen atoms at the bridgehead carbons are on the same face of the rings in the cis isomer but on opposite faces in the trans isomer.

Another common ring system is the norbornane, or bicyclo[2.2.1.)heptane, structure. Like decalin, norbornane is a bicycloalkane, so called because two rings would have to be broken open to generate an acyclic structure. Its systematic name, bicyclo[2.2.1 heptane, reflects the fact that the molecule has seven carbons, is bicyclic, and has three "bridges" of 2, 2, and 1 carbon atoms connecting the two bridgehead carbons. 

The German chemist J. BreclL proposed in 1935 that bicvcloalkenes such as 1-norbornene, which have a double bond to the bridgehead carbon, are too strained to exist. Make a molecular mode) of 1-norbornene, and explain Bredt s proposal. 

Rates of detritiation of the 1 and 2 positions of biphenylene and the 5 position of benzo [bjbiphenylene by lithium cyclohexylamide at 50 °C relative to benzene have been determined as 490, 7.0, and 1,865, respectively and the enhanced reactivity of the position a to the strained 4-membered ring has been attributed to the enhanced electronegativity of the strained bridgehead carbon atom. The same... 

Another kind of evidence for the Sn2 mechanism comes from compounds with potential leaving groups at bridgehead carbons. If the Sn2 mechanism is correct, these compounds should not be able to react by this mechanism, since the... 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

Many free-radical reactions have been observed at bridgehead carbons (e.g., see 14-37), ... 

No matter what the mechanism, a double bond does not go to a bridgehead carbon unless the ring sizes are large enough (Bredt s rule, see p. 188). This means, for example, not only that 19 gives only 20 and not 21 (indeed 21 is not a known compound), but also that 22 does not undergo elimination. 

The bond between the bridgehead carbons of bicyclo[1.1.0]butanes can be either normal or inverted [35]. The normal bond is stabilized by the high s-character (Scheme 16a). In this case, the hybrids on the bridgeheads Y have low s-character for the bridging Y-X bonds. Electronegative atoms X or substituents R at Y stabilize... 

These compounds are much more toxic than chlordan (Table III), and yet are stable toward alkaline reagents (15), being unable to eliminate hydrogen chloride without the formation of a double bond at a bridgehead carbon atom. Thus in this type of compound the conclusion must again be reached that dehydrochlorination with alkali and insecticidal activity have no systematic relationship. 

A cyclam derivative with an amine pendent donor attached at the bridgehead carbon atom was presynthesized from diethylaminomalonate and l,9-diamino-3,7-diazanonane in refluxing MeOH, followed by BH3-THF reduction.1507 It acts as a pentadentate ligand at pH 8.5 and forms a six-coordinate complex (592) with a water molecule sitting at the remaining axial site. 

The most distinctive features of the H and 13C n.m.r. spectra of bicyclic peroxides are provided by their bridgehead nuclei. An analysis of the data on over thirty compounds indicates that the characteristic chemical shift ranges are 5 3.7-4.8 for bridgehead protons and 8 72-89 for bridgehead carbons. 

All are tertiary halides so that attack by the S mode would not be expected to occur on (16) or (17) any more than it did on (8) (cf. p. 82). Sn2 attack from the back on the carbon atom carrying Br would in any case be prevented in (16) and (17) both sterically by their cagelike structure, and also by the impossibility of forcing their fairly rigid framework through transition states with the required planar distribution of bonds to the bridgehead carbon atom (cf. p. 84). Solvolysis via rate-limiting formation of the ion pair (SN1), as happens with (8) is... 

In cyclic systems, the usual simple requirements of Saytzev or Hofmann rules may be overridden by other special requirements of the system, e.g. the preference for elimination from the truns-diaxial conformation in cyclohexane derivatives (cf. p. 255). Another such limitation is that it is not normally possible to effect an elimination so as to introduce a double bond on a bridgehead carbon atom in a fused ring system (Bredt s rule), e.g. (47) (48) ... 

In 2003, Williams and Mander reported a method designed to access the hetisine alkaloids (Scheme 1.3) [27]. This approach, based upon a previously disclosed strategy by Shimizu et al. [28], relied on arylation of a bridgehead carbon via a carbocation intermediate in the key step. Beginning with (1-keto ester 46, double Mannich reaction provided piperidine 47. Following a straightforward sequence, piperidine 47 was transformed to the pivotal bromide intermediate 48. In the key step, bromide 48 was treated with silver (I) 2,4,6-trinitrobenzenesulfonate in nitro-methane (optimized conditions) to provide 49 as the most advanced intermediate of the study, in 54 % yield. 

---