Bridgehead double bond

In determining whether a bicyclic system is large enough to accommodate a bridgehead double bond, the most reliable criterion is the size of the ring in which the double bond is located. Bicyclo[3.3.1]non-l-ene" (112) and bicyclo[4.2.1 ] non-l(8)ene (113) are stable compounds. Both can be looked upon as derivatives of tra 5-cyclooctene, which is of course a known compound. Compound 112 has been shown to have a strain energy of the same order of magnitude as that of... 

Entry 4 involves nitrogen participation and formation of an iminium ion that is reduced by NaBH4. The reaction in Entry 5 creates an 11-methylenebicyclo[4.3.1]undecen-3-one structure found in a biologically active natural product. Note that this fragmentation creates a bridgehead double bond. Entry 6 involves construction of a portion of the taxol structure. The reaction in Entry 7 is stereospecific, leading to the E-double bond. 

Another epoxidation, followed by fragmentation gave the bicyclic intermediate that contains the eight-membered ring and bridgehead double bond properly positioned for conversion to Taxol (Steps B-2 and B-3). 

Palladocyclopentadiene reagent promotes [2 + 2]-cycloaddition of suitably positioned enynes to form cyclobutenes which undergo symmetry allowed ring opening to form 1,3-dienes with a bridgehead double bond (equation 149)264. 

The reaction of 177 with nBuLi in the presence of DPIBF at -78°C produced the [4 + 2]-adduct in good yield. The bridgehead double bond of 178 served as the dieno-phile [144]. 

Maier and Schleyer (220) have studied the problem of the stability of bridgehead double bonds in bi- and polycyclic systems. They define an olefinic strain (OS) as the difference in strain energy between the olefin and its parent saturated... 

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... 

O-acetate (162), which possesses a bridgehead double bond, was established by X-ray analysis. The structures of the congeners were then related to this by a series of spectral correlations. Cinnzeylanine (163) and its desacetoxy alcohol, cinnzeylanol, are insecticidal polyhydroxylated pentacyclic diterpenoids, which were isolated from Cinnamonum zeylanicum. Their structure, which is similar to that of ryanodine, was established by X-ray analysis. 

Another group of compounds that have a twisted double bond are the bicyclic compounds with bridgehead double bonds such as 1,2-norbomene (9) and 1,7-norbornene (10). " It has been found that many compounds, such as 11, which is based on trawi-cyclooctene, may be isolated whereas those based on smaller trauj -cycloalkenes are usually quite unstable. Some evidence for the formation of 9 has been obtained by trapping the product of the dehalogenation of 1,2-diha-lonorbornanes." Here, the simplest view is that the two p orbitals that form the double bond in 9 and 10 are roughly perpendicular to each other. However, pyr-amidalization and rehybridization also are involved. One indication is the reduced localized 7i-orbital population found in the NBO analysis. Whereas normal alkenes have 71 populations of 1.96 e, for 9 with OS = 57 kcal/mol, it is 1.921, and for 10 with OS = 86 kcal/mol, it is 1.896. With 9, the deviations of the a and n orbitals from the line of centers are 24° and 19°, respectively, and with 10, the deviations are 34° and 29°. 

For somewhat over seventy years, the structural proscription against bridgehead double bonds known as Bredt s rule has provided a guiding principle for strained molecules. More precisely, it is suggested that bicyclo m.n./ alk-l-ones are destabilized for small, but nonzero, m, n and p. The enthalpy of formation of three such species is available54 from hydrogenation calorimetry. These are the isomeric bicyclo[3.3.1]non-l-ene (22a), bicyclo[4.2.1]non-l-ene (22b) and bicyclo[4.2.1]non-l(8)-ene (22c), bicyclo[4.2.1]non-A18-ene) with gas-phase enthalpies of formation of 31, 74 and 50 kJ mol-1, respectively. These three numbers alone inadequately address the issue of bridgehead destabilization because the alicyclic carbon skeleton is not the same for all three olefins. 

Generally, bicyclic compounds (71) containing a bridgehead double bond and with S 5 7 may be regarded as an anti-Bredt s rule compound, which is quite unstable because of high ring strain energy (33). 

Warner, P. M. Strained bridgehead double bonds. Chem. Rev. 1989, 89,1067-1093. 

Philip M. Warner Strained Bridgehead Double Bonds, Chem. Rev. 89, 1067-1093 (1989)... 

This cyclization is particularly impressive as the corresponding base-catalysed reaction on the keto-ester does not occur because a stable enolate cannot be formed—it would have an impossible bridgehead double bond. 

Simultaneously, Woodward and co-workers (21) confirmed structure X for the alkaloid by chemical methods. They first recorded the caly-canine synthesis already mentioned. The intermediate tetraaminodi-aldehyde, first postulated by Robinson and Teuber (10), was also the basis for their structural speculations. The mercuric acetate oxidation product (dehydrocalycanthine) of Marion and Manske (13), formed by loss of two hydrogens, was smoothly converted by the action of alcoholic alkali into methylamine, and the resulting amide alcohol was written as XI. It was concluded that dehydrocalycanthine is an ene-imine, the relevant portion of the molecule being shown as XII. Other structures derivable from the tetraaminodialdehyde would more probably generate on amidine, and this would be impossible with X because of steric strain at a bridgehead double bond. 

If you build a model of 1-norbomene, you will find that it is almost impossible to form the bridgehead double bond. -Hybridization at the double bond requires all carbons bonded to the starred carbons to lie in a common plane in order for the p orbitals to overlap to form the 7t bond.The bicyclic ring system forces these atoms out of plane, and the bridgehead double bond can t form. 

Ordinarily, p-diketones are acidic because they can form enolates that can be stabilized by delocalization over both carbonyl groups. In this case, loss of the proton at the bridgehead carbon doesn t occur because the strained ring system doesn t allow formation of the bridgehead double bond. Instead, enolization takes place in the opposite direction, and the diketone resembles acetone, rather than a P-diketone, in it pKa and degree of dissociation. 

The sila- /r-Bredt olefins (olefins with bridgehead double bond) were obtained starting from 59, as a key intermediate. Thus, addition of dibromo- or chlorofluorocarbene to 59 gave the crude 60, which was converted in ethanol to 4-silabicyclo[5.3.1]undec-l(ll)-ene 61 (Scheme 12). Molecular structure of 61 was confirmed by X-ray crystallographic studies <2001JOC1216>. 

The photochemical formation of cyclobutanols is substantially favored if the ethylene that would be formed in a type II elimination must have a bridgehead double bond.120) Jn 1-adamcUitylacetone, 77, the strain is sufficient to substantially inhibit the elimination of acetone from the molecule ion. 12 ) Cyclobutanol formation is the virtually exclusive photochemical pathway for 71 and related bridgehead acetone derivative. 

A final useful pattern incorporates one double bond into a spiro ring, leading via oxy-Cope rearrangement to bicyclic ring systems with bridgehead double bonds (equation 63). " ... 

A final class of oxy-Cope rearrangements leading to cyclodecenones is represented by spirodienol (120), which rearranges to a bicyclic ketone (121) containing a bridgehead double bond. ITie related alkynic alcohols (122) behave similarly, but when R is H the initial product imdergoes an intramolecular Michael addition to afford (123). 

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