Bredt’s rule

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. 

This apparent characteristic enhancement in the basicity has been used quite frequently for the determination of the position of a double bond with respect to the nitrogen atom in unsaturated amines. The cases such as neostrychnine (134) and dehydroquinuclidine (139) in which the protonation at the 8-carbon atom cannot occur due to the lack of overlap between the electron pair on the nitrogen atom and the tt electrons of the double bond, since this would involve the formation of a double bond at the bridgehead— a violation of Bredt s rule—show a decrease in basicity. For instance the basicities of quinuclidine (140) and dehydroquinuclidine (139) have been shown by Grob et al. (82), to differ by 1.13 pK units in aqueous solution at 25. This decrease in basicity has been attributed to the electron-withdrawing inductive effect of the double bond. 

The simplest examples of this type of compound are enamines derived from the quinuclidine skeleton (67). The formulation of enamines of qflmuclidine in a inesomeric form would violate Bredt s rule. Actually, the ultraviolet spectrum of 2,3-benzoquinuclidine shows that there exists no interaction of aromatic ring tt electrons and the nitrogen-free electron pair (160,169). The overlap of the olefinic tt orbital and the lone pair orbital on nitrogen is precluded. 

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. 

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. 

As in the El-E2-ElcB mechanistic spectrum, Bredt s rule applies and if a double bond is present, a conjugated system will be preferred, if sterically possible. Apart from these considerations, the following statements can be made for Ei eliminations ... 

Selective oxidations are possible for certain bicyclic hydrocarbons.285 Here, the bridgehead position is the preferred site of initial attack because of the order of reactivity of C—H bonds, which is 3° > 2° > 1°. The tertiary alcohols that are the initial oxidation products are not easily further oxidized. The geometry of the bicyclic rings (Bredt s rule) prevents both dehydration of the tertiary bridgehead alcohols and further oxidation to ketones. Therefore, oxidation that begins at a bridgehead position... 

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) ... 

The only difference between the two reactions evidently consists in the shift of the double bond in respect of the methyl group, from a, b, to b, c. For between a and b, through stereochemical reasons, no double bond can exist, since, in accordance with Bredt s rule, none of the C-atoms which are common to both rings of a bicyclic system of the camphene type can take part in an unsaturated linkage. 

All the amendments to Bredt s rule that have been presented in the past decade have been more or less violated. One reason for these failures is that the past rules ignored the strain in parts of the molecule other than at the bridgehead double bond. Schleyer defines the strain at the bridgehead double bond, or olefin strain (OS), as the difference in strain between the olefin and the parent hydrocarbon, analogous to for carbonium ions (293). He... 

EDITING MECHANISMS BRANCHING ENZYME BRANCHPOINT BREATHING Bredt s Rule,... 

Bredt s rule and the blocked conformation (see Section n.A) precludes the ally lie alcohol formation, such as norbomene oxide jjowever, it has been very seldom... 

By now many sorts of reactive intermediates, such as free radicals, carbocations, carbenes, benzynes, and Bredt s rule violating olefins, have been generated and isolated under conditions permitting full structural characterizations. Theory-based structural parameters are generally in nearly perfect agreement with experimentally determined values. 

This theory agrees with the later results of van Tamelen and Baran (58JA4659), who were able to get N-benzylcytisin (43) from the bicyclo-substituted pyridinium salt 42 via Decker oxidation. Since formation of an anhydro base 45 is violated according to Bredt s rule, an equilibrium between 44 and a C-6 pseudobase can exist, the latter being dehydrated to yield 43 (Scheme 9). 

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