Bridgehead positions alkenes

This difference is obviously due to the difficulty in producing a double bond at a bridgehead position. Nevertheless, elimination of lithium fluoride does occur, especially at reflux temperatures the bridgehead alkene 10.8A, which probably has only a transitory existence or may even be more appropriately described as a diradical, may be trapped with furan. 

An example employing an aza-alkene (an imine) in reaction with a diene is shown in Scheme 5.20. This is a reaction that has found use in the constmction of alkaloids having nitrogen at a bridgehead position. 

Bredt was unable to explain this absence of double bonds at the bridgehead position, but was alert enough to note the phenomenon—the absence of molecules with double bonds at the bridgehead. That there could not be such compounds has become deservedly known as Bredt s rule. What is the reason behind this rule First of all, the rigid cage structure with its pyramidal bridgehead carbons (Fig. 3.44) requires that the 7t bond, the double part of the alkene, be formed not from If Ilf overlap, but by 2 /hybrid orbital overlap. Overlap is not as good as in a normal alkene n system (Fig. 3.45). There is even more to this question, however, and a... 

Thioethers. Bridgehead positions in hydrocarbons are functionalized as butyl-thioethers by reaction with lead tetra-acetate and butanethiol (c/. ref. 1). Reductive sulphidation of aldehydes is accomplished by conversion to a silyl monothio-acetal and cleavage of the C-O bond as outlined in Scheme 38. Reaction of primary alcohols with aryl isothiocyanates and triphenyl phosphine produces arylalkylthioethers, presumably via the sequence of Scheme 39. In secondary and tertiary cases elimination (to ArSH and alkene) from (76) is a competing process. 

The utility of lOOC reactions in the synthesis of fused rings containing a bridgehead N atom such as pyrrolizidines, indolizidines, and quinolizidines which occur widely in a number of alkaloids has been demonstrated [64]. Substrates 242 a-d, that possess properly positioned aldoxime and alkene functions, were prepared from proline or pipecolinic acid 240 (Eq. 27). Esterification of 240 and introduction of unsaturation on N by AT-alkylation produced 241 which was followed by conversion of the carbethoxy function to an aldoxime 242. lOOC reaction of 242 led to stereoselective formation of various tricyclic systems 243. This versatile method thus allows attachment of various unsaturated side chains that can serve for generation of functionalized five- or six-membered (possibly even larger) rings. 

An alternative substrate design, in which the alkene radical cation is substituted only at the internal position, forces the nucleophilic cyclization into the endocyclic mode, leading overall to bicyclic systems with a bridgehead nitrogen (Scheme 31) [139,140]. 

Benzvalene (18) is a tricyclic benzene isomer containing a bicyclobutane ring system bridged by an ethylene moiety its radical cation is accessible by PET or radiolysis. CIDNP indicated negative hfcs for the alkene protons (H ), strong positive hfcs for the non-allylic bridgehead protons (Hy), and negligible hfcs for the... 

Directed lithiation A new route to bridgehead alkenes based on a deprotonation reaction has been established 55 The deprotonation of 9-oxabicyclo[3.3.1]nonadiene (10) with r-RnT.i-TMF.DA occurs selectively in the allylic position. While (10) has four allyl positions, only one bridgehead proton is removed, as demonstrated by quenching with Me3SnCl, Me3SiOTf, and Me3PbCl (Scheme 6). 

Annulation reactions are possible when a precursor monocyclic substrate contains an activated alkene in a tether [4a]. As demonstrated in Scheme 5, an ester was employed to activate the olefin appended to cycloalkanone 17. Upon generation of the 0-stannyl ketyl with tributyltin hydride, the carbon-centered radical attacks the electron-poor /(-position on the activated alkene. The corresponding cyclized adduct 18 is a bicyclic skeleton with a bridgehead hydroxyl group. An example of this reaction shows cyclopentanone 19 undergoing cyclization to diquinane 20 and tricycle 21 (76 24) in 69% yield. The presence of reasonable amounts of the minor, yet readily isolable, jn-diastereomers in the reaction indicated that the reaction may not be reversible. 

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