Synthesis of Adamantanoid Ketones from Bridgehead Alcohols by the Hypoiodite Thermolysis-Cyclization Sequence

Article abstract of DOI:10.1021/jo01312a015

Thermolysis of tertiary polycyclic hypoiodites followed by base-promoted C-alkylation of the resulting iodoketones appears to be an excellent synthetic route to a number of adamantaniod ketones.The hypoiodites can be prepared readily from the corresponding alcohols by the action of Pb(OAc)4 and iodine and thermolyzed in a single operation. 6-Protoadamantanol yielded 70 percent of a 3:2 mixture of 4-homobrendan-4-one (tricyclo<5.2.1.0^3,8>decan-4-one) and 2-homobrendan-2'-one (tricyclo<5.2.1.0^4,8>decan-3-one); 3-noradamantanol produced 30 percent of a 2:1 mixture of tricyclo<3.3.1.0^2,7>nonan-3-one and 1-hydroxy-2-oxaadamantane, while 4-homoisotwistan-3-ol gave exclusively the elimination product, 8-methylenebicyclo<4.4.0>decan-2-one.This route has been successfully used also in the preparation of protoadamantan-4-one, 10-homoprotoadamantan-4-one (tricyclo<4.3.2.0^3,8>undecan-4-one) and 4-homoprotoadamantan-4-one (tricyclo<5.3.1.0^3,9>undecan-4-one).The direction of α-CC bond scission in the thermolysis of polycyclic hypoiodites appears to be controlled by the relative thermodynamic stabilities of the intermediary carbonylalkyl free radicals.In most cases this can be approximated simply by combination of the relative strain energies of the corresponding hydrocarbons and the relative stabilities of the free-radical centers.The course of intramolecular C-alkylation of polycyclic ketones is controlled by the balance of at least three factors: preferential enolization, the size of the smallest ring to be formed, and the degree of distortion of the prefered collinear arrangement of the enolate α-carbon atom and the carbon-leaving group bond.