Efficient Cu-Catalyzed Asymmetric Conjugate Additions of Alkylzinc Reagents to Aromatic and Aliphatic Acyclic Nitroalkenes

Abstract

An efficient and highly enantioselective (up to 95% ee) Cu-catalyzed method for asymmetric conjugate addition (ACA) of alkylzinc reagents to acyclic disubstituted nitroalkenes is presented. Reactions are typically effected at ambient temperature in the presence of 2 mol % chiral dipeptide phosphine and 1 mol % (CuOTf)(2).C(6)H(6). Nitroalkenes bearing aromatic as well as aliphatic substituents readily undergo asymmetric additions. [reaction: see text]

Design and synthesis of new bidentate alkoxy-NHC ligands for enantioselective copper-catalyzed conjugate addition

“…In order to generalize the use of our alkoxy-NHC 6a in the enantioselective conjugate addition, we next screened several other Michael acceptors with acyclic enones [20] and nitroalkenes [21,22]. These substrates, which are known to be problematic, were tested under identical conditions at ambient temperature.…”

Catalytic Asymmetric Synthesis With Novel Monodentate Phosphorus Ligands

“…65,66 Accordingly, this reaction has been extensively studied in recent years with the development of chiral mono dentate phosphorus ligands. 16,18,21,[67][68][69][70][71][72] Most notably, Feringa 2,66,73 and Alexakis 63 have developed chiral monodentate phosphoramidite ligands for this reaction, and their best ligands are L22 and L23, respectively. However, the scope of this reaction is still very limited in terms of substrate structures and dialkylzinc species.…”

“…16,63,73 In particular, the reaction of dialkylzinc with aromatic nitroalkenes still remains challenging, even using L22 (up to 69% ee) or L23 (82% ee). 63,68,72,73 Thus, we have evaluated the efficacy of our monophosphoramidite ligands in the Cu-catalyzed conjugate addition of diethylzinc to trans-βnitrostyrene and its derivatives. First, a preliminary screening of effective ligands was performed using trans-β-nitrostyrene as the substrate in order to establish a possible structure-efficiency relationship.…”

Nitroalkenes as Amination Tools

“…Chiral dipeptide phosphines 3 require the presence of copper(I) salts to produce high levels of enantioselection. Catalytic reduction of the resulting nitroalkanes provides the corresponding amines in enantioenriched form (Scheme 3.6 ) [22] .…”