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

The Pd-catalyzed cross coupling of either alpha-haloenones with organometals or alpha-metalloenones with organic halides is intrinsically more problematical than the corresponding reaction of beta d-substituted enones or ordinary alkenyl derivatives. Nonetheless, satisfactory procedures have been developed for cross coupling with organometals containing Zn, Sn, B and Cu to give alpha-organylenones in high yields. As in the other cases, organozincs generally display the highest reactivity. In highly demanding and/or delicate situations, some indirect protocols involving protection of carbonyl groups or their temporary reduction help overcome difficulties encountered in direct alpha-substitution. Conjugate reduction and conjugate addition of alpha-substituted enones provide the corresponding saturated carbonyl compounds in completely regiocontrolled manner. Together with the ability to accommodate unsaturated organic groups, such as aryl, alkenyl, and alkynyl, the new Pd-catalyzed alpha-substitution protocols developed since 1987 promise to become synthetic tools of widespread application. (C) 1999 Elsevier Science S.A. All rights reserved.