Nickel-Catalyzed Conjugate Addition of Alkenylzirconium Species to α,β-Unsaturated Ketones

Alkenylzirconium(IV) complexes, prepared by hydrozirconation of the corresponding acetylenes with Cp₂Zr(H)Cl (Cp = η⁵-C₅H₅), can be utilized in conjugate addition to α,β-enones, catalyzed by Ni(AcAc)₂ (AcAc = 2,4-pentanedionate). No 1,2 addition of the alkenyl group is observed, and no trans-cis isomerization occurs. Conjugate addition of terminal alkenyls proceeds faster than that of internal alkenyls. The product of conjugate addition to α-substituted cyclic enones is the trans-1,2-disubstituted cyclic ketone. Attempts to catalyze conjugate addition of alkylzirconium species to α,β-enones using nickel complexes have not been successful. The active form of the catalyst is postulated to be a reduced nickel species, generated by transfer of alkenyl groups from Zr to Ni(II), followed by reductive elimination of diene. It is found that reduction of Ni(AcAc)₂ with 1 equiv of DiBAH, prior to reaction, gives an efficient catalyst for improved yields in the case of conjugate addition. Co(AcAc)₂ and Pd(AcAc)₂/DiBAH were found comparable to Ni(AcAc)₂ as effective conjugate addition catalysts. Applications of this conjugate addition reaction to synthesis of prostaglandin analogues are described.