Steroidal allylic fluorination using diethylaminosulfur trifluoride: A convenient method for the synthesis of 3β-acetoxy-7α- and 7β-fluoroandrost-5-en-17-one

摘要

This paper discusses our findings regarding fluorination of the diastereomeric 3β-acetoxy-7-hydroxyandrost-5-en-17-ones (3 and 4) at the allylic 7-hydroxyl group using diethylaminosulfur trifluoride under various experimental conditions. The reaction led to the formation of allylic 7α- and 7β-fluoro derivatives, 6 and 7, contaminated with small amounts of 3β-acetoxy-5α-fluoroandrost-6-en-17-one (8), the rearrangement product, and 3β-acetoxyandrosta-4,6-dien-17-one (9), the elimination product. However, synthesis of 3β-acetoxy-7α-fluoroandrost-5-en-17-one (6) and 3β-acetoxy-7β-fluoroandrost-5-en-17-one (7) has been achieved in high isonieric purity by careful manipulation of the experimental conditions. Also included herein is a convenient chemical synthesis of pure 3β-acetoxy-7α-hydroxyandrost-5-en-17-one (4) and 3β-acetoxy-7β-hydroxyandrost-5-en-17-one (3), the starting materials for the present fluorination reaction. The structure of a degradation product, 3β-acetoxy-5α-hydroxyandrost-6-en-17-one (5), has been established by X-ray diffraction analysis to ascertain unambiguously its absolute configuration.