Bredt

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. 

When distilled with phosphorus pentoxide, camphor yields cymene, and with iodine, carvacrol. Both of these bodies are para-derivatives of benzene. On oxidation with nitric acid camphor yields many acids, of which the chief are camphoric acid, CjgHjgO, camphanic acid, CjoHj O, and camphoronic acid, CgHj Og. The constitution of these acids has an important bearing on that of camphor. Many formulae have been suggested for camphor during the past few years, but that of Bredt is now universally accepted, and has received complete confirmation by Komppa s synthesis of camphoric acid. This synthesis confirms the formula for camphoric acid as—... 

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. 

Chromium aminocarbenes [39] are readily available from the reaction of K2Cr(CO)5 with iminium chlorides [40] or amides and trimethylsilyl chloride [41]. Those from formamides (H on carbene carbon) readily underwent photoreaction with a variety of imines to produce /J-lactams, while those having R-groups (e.g.,Me) on the carbene carbon produced little or no /J-lactam products [13]. The dibenzylaminocarbene complex underwent reaction with high diastereoselectivity (Table 4). As previously observed, cyclic, optically active imines produced /J-lactams with high enantioselectivity, while acyclic, optically active imines induced little asymmetry. An intramolecular version produced an unusual anti-Bredt lactam rather than the expected /J-lactam (Eq. 8) [44]. 

Still another example is the easy formation of anti-Bredt bicycloalkenones (see p. 188). As indicated above, a,a -dihalophosphoranes can be used to prepare 1,1-dihaloalkenes. Another way to prepare such compounds is to treat the carbonyl compound with a mixture of CX4 (X Cl, Br, or I) and triphenylpho-sphine, either with or without the addition of zinc dust (which allows less Ph3P to be used). " ... 

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 ... 

Bredt DS, Snyder SEl Nitric oxide, a novel neuronal messenger. Neuron 8 3—11, 1992 Brouette T, Anton R Clinical review of inhalants. Am J Addict 10 79-94, 2001 Brown ES, Nejtek VA, Perantie DC, et al Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord4 406 11, 2002 Bushnell PJ, Evans EIL, Palmes ED Effects of toluene inhalation on carbon dioxide production and locomotor activity in mice. Fundam Appl Toxicol 5 971-977, 1983... 

Bredt, DS and Synder, SH (1994) Nitric oxide a physiologic messenger molecule. Trends Biochem. Sci. 63 175-195. 

The Ramberg-Backlund reaction of compound 384 gave the Bredt olefin 388, which was actually isolated . By reaction of chlorosulfones 385-387 and 392-394 (n = 2) with potassium t-butoxide the corresponding oxaproperanes 392-397 were obtained by the Ramberg-Backlund reaction, but only in low yields . In contrast, the reaction of the chlorosulfoxides 392, 393 and 394 n = 1) gave oxaproperanes 395, 396 and 397 under analogous conditions in 85-90, 25 and 85% yields, respectively . 

Dawson, V.L., Dawson, T.M., London, E.D., Bredt, D.S. and Snyder, S.H. (1991). Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl Acad. Sci. USA 88, 6368-6371. 

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... 

Bredt, D. S. Snyder, S. H. (1992). Nitric oxide, a novel neuronal messenger. Neuron 8, 3 11. 

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) ... 

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