Over the past several decades, chemists have developed a number of synthetic
methodologies for the synthesis of steroid hormones. One of these, developed
by Lutz Tietze at the Institut für Organische Chemie der Georg-August-
Universität, Göttingen, Germany, used a double Heck reaction to create ring B
of the steroid nucleus. As shown in the following retrosynthetic analysis, a
key intermediate in his synthesis is compound (1). Two Heck reaction
disconnects of this intermediate give compounds (2) and (3). Compound (2)
contains the aromatic ring that becomes ring A of estrone. Compound (3)
contains the fused five- and six-membered rings that become rings \(C\) and \(D\)
of estrone.
(a) Name the types of functional groups in estrone.
(b) How many chiral centers are present in estrone?
(c) Propose structural formulas for compounds (2) and (3).
(d) Show how your proposals for compounds (2) and (3) can be converted to
compound
(1). (Note: In the course of developing this synthesis, Tietze discovered that
vinylic bromides and iodides are more reactive in Heck reactions than are aryl
bromides and iodides.)
(e) In the course of the double Heck reactions, two new chiral centers are
created. Assume in compound (3), the precursor to rings \(C\) and \(D\) of
estrone, that the fusion of rings \(C\) and \(D\) is trans and that the angular
methyl group is above the plane of the ring. Given this stereochemistry,
predict the stereochemistry of compound (1) formed by the double Heck
reaction.
(f) To convert (1) to estrone, the tert-butyl ether on ring D must be
converted to a ketone. How might this transformation be accomplished?
