Organometallic Routes to Novel Steroids Containing Heterocyclic C-17 Side-Chains

A range of novel steroid analogues bearing a C-17 side-chain containing a 20R-hydroxyl group and a variety of heterocyclic substituents have been prepared by organometallic additions to 3-methoxypregnenolone. X-ray crystallography has been used to establish that the organometallic additions proceed with excellent Felkin-Anh control. This methodology has been extended, by use of the Achmatowicz rearrangement and ring-closing metathesis approaches, to prepare pyrandione and δ-lactone steroidal analogues reminiscent of the withanolide natural products.