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
E. Negishi, 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, J ORGMET CH, 576(1-2), 1999, pp. 179-194
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.