Bridgehead positions reduction

Scheme 3-54). This transformation constitutes a cascade of an intramolecular Heck insertion and subsequent heterocyclization. The initially formed arylpalladium species attacks the bridgehead position of the diene functionality in 238 to foim a JT-allylpalladium complex which is trapped by the internal nucleophilic phenol moiety (cf. Scheme 3-26). Since the starting diene 238 can be prepared in both enantiomeric forms by asymmetric reduction of a ketone, this sequence allows the preparation of both the natural morphine and its unnatural enantiomer. 

The electrophilic bromine cation can also be generated from A -bromosuccinimide (NBS). When 2-methylene-6,6-dimethylbicyclo[3.1.0]hexane with an ester function at the bridgehead position was treated with NBS in diethyl ether the electrophilic attack took place at the terminal position of the C—C double bond and the cyclopropane ring was opened to give a cyclopentene derivative. Due to the lack of a reactive nucleophile, a proton was eliminated. The reduction of the ester function did not change the course of this reaction. With tert-hvAy hypochlorite, the corresponding chloro product was obtained. ... 

Compound C has a double bond situated at a bridgehead atom. This is a violation of Bredt s rule, which states that bicyclic compounds cannot have a double bond at a bridgehead position due to extremely poor overlap of the p orbitals involved in the tt bond. Only very large bicyclic compounds ([6.2.6] and bigger) can have a double bond at bridgehead positions due to a reduction in angle strain. Since compound [1] is a relatively small bicyclo compound ([2.2.2.]), compound C will exist only in negligible amounts. 

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. 

Evidently, these or closely related intermediates are accessible and reactive, since the synthesis was successfully achieved as outlined in Scheme 13.28. In addition to the key cationic cyclization in Step D, interesting transformations were carried out in Step E, where a bridgehead tertiary alcohol was reductively removed, and in Step F, where a methylene group, which was eventually reintroduced, had to be removed. The endocyclic double bond, which is strained because of its bridgehead location, was isomerized to the exocyclic position and then cleaved with Ru04/I04. The enolate of the ketone was then used to introduce the C(12) methyl group in Steps F-3 and F-4. 

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