Bridgehead halides reduction

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

A theoretical study was performed to determine the stability of bicycloalkyl halide radical anions as well as the dependence of the reduction potential of the corresponding neutral compounds on the angular strain energy of the parent hydrocarbons. It was proposed that an increase in strain at the bridgehead carbon is accompanied by a decrease in the photostimulated outer-sphere ET rate for the parent RX compounds43. 

A classical method using Na- or Li-liquid ammonia (Birch reduction conditions) is effective for reductive dehalogenations of aryl and vinylic halides, but it is not always successfully applied to alkyl halides, although cyclopropyl halides and bridgehead halogens are exceptions.Under such conditions, the reactions are often accompanied by side reactions, such as elimination, the Wurtz coupling reaction, cyclization and reduction of carbonyl compounds. An example, a synthesis of pentaprismane (1), is shown in Scheme 4. ... 

A currently employed method for dehalogenation of alkyl halides is to use a Li- or Na-alcohol reagent system. This method is effective not only for simple alkyl halides but also for the reduction of a halogen atom attached to a bridgehead. Carbon-carbon unsaturated bonds are not affected under the conditions, as shown in Scheme 5. ... 

Exchange of the bromine atoms in 142 and 145 for other halides or hetero-atomic groups is similarly facile [100]. Among those listed in Scheme 31, the triazides 154 and 158 are interesting because of their further conversion. Reduction of 154 with lithium aluminium hydride furnishes the C3v-symmetrical triamine 155 [105] (cf. Scheme 33 for the Cs-symmetrical isomer). The homologue 158 was converted into unusual heterocycles by thermolysis [100] (cf. Scheme 43). Three-fold bridgehead ethers such as 159 and 160 were obtained by alcoholysis of 142, and Ag1 ion assisted reaction of 142 with tert-butyl hydroperoxide afforded the tris(peroxide) 161 [100]. 

Studies of tin hydride reductions of bridgehead aliphatic halides have been interpreted as indicating little or no charge separation in the transition state Fort, R.C., Jr. Hiti, J./. Org. Chem. 1977,42, 3968. However, positive slope of the Hammett plot / = 1.4 points toward some participation of ET with partial negative charge generation at the transition state. 

The initial studies centered on the 1-norbomyl halides 8. On irradiation in CH3OH, they afford a mixture of the reduction product norbornane (9) and the ether 10, with the former predominating from bromide 8b and the latter from iodide 8a. The reduction product 9 arises via abstraction of a hydrogen atom by 1-norbornyl radical from the medium and ether 10 via nucleophilic trapping of the 1 -norbornyl cation. Irradiation of either hahde in CH3OD afforded ether 10 with no detectable incorporation of deuterium, indicating that it does not arise via acid-catalyzed addition of the alcohol to an initially formed unsaturated intermediate such as the bridgehead alkene 12 or the propeUane 13. 

The photobehavior of alkyl halides varies with structure, depending on the ease of P-ehmination. Bridgehead and Related Halides Nucleophilic Trapping vs. Reduction... 

---