Stereochemical Effects in Cyclopropane Ring Openings: Biomimetic Ring Openings of All Isomers of 22,23-Methylenecholesterol Acetate

By using the unique stereochemistry of the side chain in cholesterol, the dynamic influence of proximate chiral centers on the acid-promoted isomerizations of cyclopropanes is defined. Unexpectedly, when the cyclopropane is placed in the 22,23 position, either a backbone rearrangement is induced or a priori unanticipated side-chain olefins arise, each dependent on the stereochemistry of the cyclopropane starting material. The synthesis and sterochemical assignments of the four possible 22,23-methylenecholesterol acetates [22R.23R (22), 22S,23S (23), 225,23R (24), 22R.23S (25)] are reported as well as the effect of stereochemistry on the acid-promoted isomerization of these compounds. Isomers 22 and 23 under the conditions of ring opening yield unexpected backbone rearrangement products of the 3β-acetoxy-(17S)-17,23-dimethyl-18-normethyl-cholest-5,13(14)-diene type (32–35), which can also be obtained from rearrangement of the Δ^5,20(22)- and Δ^5,17(20)-23-methylcholestadien-3β-ol acetates (42, 44, 53, 54). The stereochemical criteria governing the course of these isomerizations are discussed.