Synthesis of Diastereomeric 8-Fluoro-ABC-Steroid Building Blocks

An eight-step linear sequence for the preparation of two diastereomers of an 8-fluoro-ABC-steroid building block was developed. Key step was an intramolecular Diels–Alder reaction of an intermediate o-quinodimethane formed from a benzocyclobutene substituted with a 5-fluorohex-5-en-4-one chain. This side chain was prepared from 6-chlorohex-1-ene by bromofluorination, elimination of HBr, Finkelstein reaction and alkylation of a literature-known benzocyclobutene derivative with the thus-formed 6-iodo-2-fluorohex-1-ene. Allylic oxidation of side chain's fluorovinyl moiety to an α-fluoro-α,β-unsaturated ketone completed the preparation of the precursor for the [4+2]-cycloaddition.