Stereoselective Preparation of Vitamin D Precursors Using the Intramolecular Coupling of Alkynes and Cyclopropylcarbene-Chromium Complexes: A Formal Total Synthesis of (±)-Vitamin D3

Article abstract of DOI:10.1021/jo972186z

The intramolecular coupling of alkynes and cyclopropylcarbene-chromium complexes has been examined. Complexes that feature a stereogenic center at the propargylic position of the alkyne- carbene tether are the focus of this paper. The reaction produces a cyclopentadienone intermediate fused to an oxygen heterocycle, which is reduced to the corresponding cyclopentenone under the reaction conditions (100 °C in 1% aqueous toluene). The preexisting stereogenic center has a powerful influence on the reduction of the cyclopentadienone ring, and predominantly a single diastereomer is produced in the reaction. Reductive cleavage of the heterocyclic ring with retention of stereochemistry affords compounds featuring a stereocenter on the five-membered ring and on a side chain. Use of the above reaction processes for the synthesis of the vitamin D precursor de-ABC-cholestan-14-one is also discussed.