Novel and selective alpha-substitution of ketones and other carbonyl compounds based on Pd-catalyzed cross coupling of alpha,beta-unsaturated carbonyl derivatives containing alpha-halogen or alpha-metal groups

The Pd-catalyzed cross coupling of either alpha-haloenones with organometal s or alpha-metalloenones with organic halides is intrinsically more problem atical than the corresponding reaction of beta d-substituted enones or ordi nary alkenyl derivatives. Nonetheless, satisfactory procedures have been de veloped for cross coupling with organometals containing Zn, Sn, B and Cu to give alpha-organylenones in high yields. As in the other cases, organozinc s generally display the highest reactivity. In highly demanding and/or deli cate situations, some indirect protocols involving protection of carbonyl g roups or their temporary reduction help overcome difficulties encountered i n direct alpha-substitution. Conjugate reduction and conjugate addition of alpha-substituted enones provide the corresponding saturated carbonyl compo unds in completely regiocontrolled manner. Together with the ability to acc ommodate unsaturated organic groups, such as aryl, alkenyl, and alkynyl, th e new Pd-catalyzed alpha-substitution protocols developed since 1987 promis e to become synthetic tools of widespread application. (C) 1999 Elsevier Sc ience S.A. All rights reserved.