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 alpha -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 alpha -alkynylenones in excellent yields. This optimized procedure has been applied to the synthesis of (+/-)-harveynone and (+/-)-tricholomenyn A in high yields. Investigation of related alpha -alkylation reactions using alkylzincs has revealed the following. Methylzinc and primary alkylzinc derivatives readily undergo Pd-catalyzed cross coupling with alpha -iodoenones. Although (s-Bu)(2)Zn also undergoes Pd-catalyzed cross coupling, only the n-Bu-substituted products were obtained. alpha -Benzylation and alpha -homobenzylation can proceed satisfactorily, whereas allylzinc and pro pargylzinc derivatives undergo only addition to the carbonyl group. Although some promising results have been obtained in alpha -homoallylation and alpha -homopropargylation, these reactions need to be further improved. (C) 2000 Elsevier Science Ltd. All rights reserved.