Novel 17α-ethynylestradiol derivatives: Sonogashira couplings using unprotected phenylhydrazines

The Pd/Cu catalyzed coupling of 17α-ethynylestradiol with halogenated amino-substrates was investigated. Iodophenylhydrazine and its protected derivatives reacted with 17α-ethynylestradiol to give 4-hydrazinophenyl derivatives without any degradation of the hydrazine group. Unprotected 3-, and 4-iodoaniline reacted similarly to produce the aminophenyl-derivatives. Protection of the amino group of halogenated benzylamines was required for alkyne coupling reactions, in order to avoid competing ortho-palladation of the benzylamine substrates.