Enantioselective Synthesis of Nitroalkanes Bearing All-Carbon Quaternary Stereogenic Centers through Cu-Catalyzed Asymmetric Conjugate Additions

Abstract

The first examples of catalytic asymmetric conjugate addition (ACA) of alkylzinc reagents to trisubstituted nitroalkenes, leading to the formation of nitroalkanes bearing a quaternary carbon stereogenic center, are reported. Reactions are promoted in the presence of 4 mol % of a readily available amino acid-based phosphine and 2 mol % (CuOTf).C6H6. Cu-catalyzed reactions proceed efficiently in up to 98% ee and can be carried out with a variety of dialkylzinc reagents and trisubstituted nitroolefins. We highlight the synthetic utility of the products obtained by efficient conversion of optically enriched nitroalkanes to the corresponding carboxylic acids.

Chiral Olefins as Steering Ligands in Asymmetric Catalysis

“…There are very few examples of conjugate additions to b,bdisubstituted a,b-unsaturated carbonyl compounds. [80] During examination of the use of substituted maleimides, Hayashi and co-workers discovered that the regioselectivity of the addition is a function of the employed ligand (Table 5). [81] Whereas Rh/binap-catalyzed processes preferably give rise to 1,4-adducts with a quaternary stereogenic center, Rh/diene catalysts lead to cis/trans mixtures of 142.…”

Asymmetric Michael addition of trisubstituted carbanion to nitroalkenes catalyzed by sodium demethylquinine salt in water

“…Several new catalysts for the enantioselective construction of quaternary carbon centers through Michael addition have been developed in recent years. [7][8][9][10][11][12] Most of these are organometallic compounds, for example, Pd complex, 13 lanthanum-sodium-BINOL(LSB) complex, 14 Rh complex, 15 Cu complex, 16 Lewis acid, 17 or base 18 . Only recently, some organocatalysts for the Michael addition of disubstituted carbanions to nitrostyrenes were reported.…”

Peptidic Amidomonophosphane Ligand for Copper‐Catalyzed Asymmetric Conjugate Addition of Diorganozincs to Cycloalkenones

“…Highly efficient phosphane ligands were also developed by Imamoto [15] and Hoveyda. [16] These phosphorus ligands were shown to be applicable in the conjugate addition reaction of nitroalkenes [17][18][19][20][21] and a,b-unsaturated lactones. [22,23] Copper-catalyzed conjugate arylation, [24,25] vinylation [26] and kinetic resolution [27] have been the topics of the recent brilliant studies.…”