Substituent-Directed Oxidation: The Syn Stereochemistry of Addition of High-Valent Oxochromium Reagents to Alkenes

Article abstract of DOI:10.1021/jo00264a015

The transannular oxidative cyclization of cycloalkenols is a useful synthetic method for the intramolecular syn alkoxyhydroxylation of an alkene, a transformation for which there is presently no alternative procedure.Under the influence of certain high-valent chromium reagents, a cycloalkene substrate that also bears a suitably disposed tertiary hydroxyl ligand first binds the oxidant and then undergoes selective oxidative attack of the tethered oxidant on the alkene.The substrate 1-methylcyclooct-4-en-1-ol (1) is oxidized in a regiospecific fashion to 1-methyl-9-oxabicyclo<4.2.1>nonan-5-one (2) by pyridinium chlorochromate (PCC), while none of the regioisomeric 1-methyl-9-oxabicyclo<3.3.1>nonan-4-one is produced.A regio- and stereospecific oxidative cyclization of 1,5-dimethylcyclooct-4-en-1-ol (3) occurs on treatment with PCC, to yield the exo alcohol isomer of 2,6-dimethyl-9-oxabicyclo<4.2.1>nonan-2-ol (4a), the result of syn oxidative addition of the hydroxyl-bound oxochromium moiety across the carbon-carbon double bond.The endo alcohol isomer of 2,6-dimethyl-9-oxabicyclo<4.2.1>nonan-2-ol (4b) is prepared for comparison by stereospecific addition of tetramethylzirconium to 2.Standard MCPBA epoxidation of 3 gives rise to a mixture of the cis epoxide, endo-1,5-dimethyl-9-oxabicyclo<6.1.0>nonan-5-ol (5), and the product of rearrangement of the trans epoxide, endo-1,5-dimethyl-9-oxabicyclo<3.3.1>nonan-2-ol (6).The cis epoxide 5 on further treatment with PCC is not converted to exo alcohol (4a), indicating that an epoxide intermediate is not involved in the highly specific transannular oxidative cyclization of 3 with chromate.