1,4-Chirality transfer via the ester enolate Claisen rearrangements in the preparation of (25R)- and (25S)-cholestenoic acids

•Claisen rearrangement of 22-allyl and 22-Propargyl alcohol ethers was investigated.•(22R)- and (22S)-Propargyl enol ethers gave the (25R)- and (25S)-isomeric allenes.•1,4-Chirality transfer methodology was applied for C-25 stereogenic center formation.•Stereochemical outcome of the Ireland-Claisen rearrangement was studied.•(25R)- and (25S)-Cholestenoic acids were prepared.

Two variants of the Claisen rearrangement were evaluated for a stereoselective construction of a C-25 stereogenic center in cholestenoic acids based on 1,4-chirality transfer. Johnson orthoester Claisen rearrangement of (22R)- and (22S)-propargyl enol ethers proceeded in a highly stereoselective manner to give (25R)- and (25S)-isomeric allenes. The stereochemical outcome of the Ireland-Claisen rearrangement of 22-allylic alcohols was dependent on the configuration of the C-22 hydroxyl group and the geometry of the enol ether. The latter could be controlled by the solvent (THF or a mixture of THF/HMPA) chosen for the generation of silyl enolate.

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