ABSTRACT
An efficient copper-catalyzed enantioselective conjugate addition of dimethylzinc to α,ß- and α,ß,γ,δ-unsaturated 2-acyl-N-methylimidazoles has been achieved using a chiral bidentate hydroxyalkyl-NHC ligand. The reactions proceeded with both excellent regio- and enantioselectivity (14 examples, 87-95 % ee) to afford the desired 1,4-adducts, which were easily transformed to the corresponding aldehydes, esters, and ketones. Subsequently, this powerful methodology was therefore successfully applied in the synthesis of natural products. Furthermore, an iterative process was also disclosed leading to highly desirable 1,3-desoxypropionate skeletons (up to 94 % d.e.).
ABSTRACT
The copper-catalyzed asymmetric conjugate addition (ACA) of nucleophiles onto polyenic Michael acceptors represents an attractive and powerful methodology for the synthesis of relevant chiral molecules, as it enables in a straightforward manner the sequential generation of two or more stereogenic centers. In the last decade, various chiral copper-based catalysts were evaluated in combination with different nucleophiles and Michael acceptors, and have unambiguously demonstrated their usefulness in the control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field.
ABSTRACT
CC coupling: DiPPAM 1 and BINAP 2 ligands led to divergent behaviors in the asymmetric conjugate addition (ACA) of dialkylzinc reagents to linear aryldienones, which were applied to the development of a highly selective sequential asymmetric 1,6/1,4-ACA process (see scheme; Tfâ =â triflate, DBUâ =â 1,8-diazabicyclo[5.4.0]undec-7-ene).
