| dc.description.abstract | The first few examples of exclusive formation of cyclopropane from homoallyl bromides via a 3-exo-trig radical cyclisation reaction are described in this chapter. Synthesis of chiral tricyclo[3.2.1.0²,?]octanes, starting from carvone via an efficient 3-exo-trig radical cyclisation of either a bicyclo[3.2.1]oct-6-en-2-yl radical or a bicyclo[2.2.2]oct-5-en-2-yl radical, has been achieved.
Thus, Grignard reaction on (S)-carvone (S–26) with 4?methylphenylmagnesium bromide followed by oxidation of the resulting tertiary alcohol 44 furnished tolylcarvone (R)–39. Regiospecific bromomethoxylation (NBS–CH?OH) on the electron-rich double bond of tolylcarvone 39 generated an epimeric mixture of the bromoenone 41.
Intramolecular alkylation of the thermodynamic dienolate obtained from bromoenone 41 with potassium t-butoxide in THF and t-butanol yielded an epimeric mixture of the bicyclo[2.2.2]octenone 43. Reaction of methoxyenone 43 with boron tribromide at low temperature rearranged the bicyclo[2.2.2]octenyl system to the bicyclo[3.2.1]octenyl system, furnishing the radical precursor bromoketone 46.
Treatment of bromoketone 46 with *Bu?SnH in the presence of a catalytic amount of AIBN generated exclusively the tricyclic ketone 51 via a 3?exo?trig radical cyclisation, without the formation of any detectable amounts of either reduced or homoallyl–homoallyl radical rearrangement products. Conversion of tolyl ketone 51 into lactone 54 via degradation of the tolyl group established the endo stereochemistry of the tolyl substituent.
Analogously, the radical precursors p? and o?anisyl compounds 62 and 64, prepared from (S)-carvone (S?26) in the same manner, furnished the tricyclic ketones 65 and 66.
On the other hand, reaction sequences starting with phenylethynylcarvone 69 generated the radical precursor bicyclo[2.2.2]oct?5?en?2?yl bromide 72 instead of the rearranged bicyclo[3.2.1]octyl compound. Even the bicyclo[2.2.2]octenyl bromide 70, on radical cyclisation, furnished the tricyclic ketone 74 via a 3-exo-trig process.
However, the ??naphthyl derivative 75 failed to cyclise, probably due to the orthogonal arrangement of the naphthyl group with the olefinic moiety caused by steric factors. This was confirmed by the 3-exo-trig radical cyclisation of ??naphthyl compounds 82 and 84, which gave the tricyclic ketone 86.
In addition, a radical annulation methodology—via intermolecular radical addition followed by 5?exo?trig cyclisation of the resulting radical, starting from bromide 75 and methyl acrylate—yielded isotwistane 90, containing a carbon framework (12 out of 15 carbons in place) identical to that present in the sesquiterpenes pupukeananes. | |
