High-pressure-mediated extension of the privileged steroid scaffold

The commercially available steroid dehydroepiandrosterone 3-acetate (DHEA) was converted into new, highly functionalized spiro derivatives by modification of the D-ring. The transformation proceeded through conversion of the C-17 carbonyl group into an electron-deficient alkene, followed by either [2+2] or [4+2] cycloaddition. The cycloaddition reactions were successful for alkylidene malononitriles and 2-cyano acrylates. Application of high pressure (15 kbar) was essential for good conversions due to the high steric hindrance on position C-17. The cycloadducts formed from the reaction of 2-cyano acrylates and Danishefsky's diene have high potential for further functionalization.