Strictly Regiocontrolled α-Monosubstitution of Cyclic Carbonyl Compounds with Alkynyl and Alkyl Groups via Pd-Catalyzed Coupling of Cyclic α-Iodoenones with Organozincs

The conditions for the Pd-catalyzed cross coupling of cyclic α-iodoenones, such as 2-iodo-2-cyclohexenone, with alkynylzincs have been optimized. The use of tris(o-furyl)phosphine (TFP) as a ligand and DMF as a solvent has led to the formation of α-alkynylenones in excellent yields. This optimized procedure has been applied to the synthesis of (±)-harveynone and (±)-tricholomenyn A in high yields. Investigation of related α-alkylation reactions using alkylzincs has revealed the following. Methylzinc and primary alkylzinc derivatives readily undergo Pd-catalyzed cross coupling with α-iodoenones. Although (s-Bu)2Zn also undergoes Pd-catalyzed cross coupling, only the n-Bu-substituted products were obtained. α-Benzylation and α-homobenzylation can proceed satisfactorily, whereas allylzinc and propargylzinc derivatives undergo only addition to the carbonyl group. Although some promising results have been obtained in α-homoallylation and α-homopropargylation, these reactions need to be further improved.