Bredt's rule

In organic chemistry, Bredt's rule is an empirical observation that states that a double bond cannot be placed at the bridgehead of a bridged ring system, unless the rings are large enough. The rule is named after Julius Bredt, who first discussed it in 1902[1] and codified it in 1924.[2] It primarily relates to bridgeheads with carbon-carbon and carbon-nitrogen double bonds.[3]

For example, two of the following isomers of norbornene violate Bredt's rule, which makes them too unstable to prepare:

In the figure, the bridgehead atoms involved in Bredt's rule violation are highlighted in red.

Bredt's rule is a consequence of the fact that having a double bond on a bridgehead, carbons from which three bonds radiate and which the rings share a single covalent bond, would be equivalent to having a trans double bond on a ring, which is not stable for small rings (fewer than eight atoms) due to a combination of ring strain, and angle strain (nonplanar alkene). The p orbitals of the bridgehead atom and adjacent atoms are orthogonal and thus are not aligned properly for the formation of pi bonds. Fawcett quantified the rule by defining S as the number of non-bridgehead atoms in a ring system, and postulated that stability required S ≥ 9 in bicyclic systems[4] and S ≥ 11 in tricyclic systems.[5] There has been an active research program to seek compounds inconsistent with the rule,[6] and for bicyclic systems a limit of S ≥ 7 is now established[3] with several such compounds having been prepared.[7] The above norbornene system has S = 5 and so they are not preparable.

Bredt's rule can be useful for predicting which isomer is obtained from an elimination reaction in a bridged ring system. It can also be applied to reaction mechanisms that go via carbocations and, to a lesser degree, via free radicals, because these intermediates, like carbon atoms involved in a double bond, prefer to have a planar geometry with 120 degree angles and sp² hybridization. The rule also allows the rationalisation of observations. For example, bicyclo[5.3.1]undecane-11-one-1-carboxylic acid undergoes decarboxylation on heating to 132 °C, but the similar compound bicyclo[2.2.1]heptan-7-one-1-carboxylic acid remains stable beyond 500 °C, despite both being β-keto acids with the carbonyl group on a one-carbon bridge and the carboxylate group on the bridgehead. The mechanism of decarboxylation involves an enolate intermediate, which is an S = 9 species in the former case and an S = 5 species in the latter, preventing the decarboxylation in the smaller ring system.[3]

An anti-bredt molecule is one that is found to exist and be stable (within certain parameters) despite this rule. A recent (2006) example of such a molecule is 2-quinuclidonium tetrafluoroborate.[8] Bridgehead double bonds can be found in some natural products, discussed in a review by Mak, Pouwer and Williams,[9] and an older review by Shea looked at bridgehead alkenes more generally.[10]