Highly Enantioselective Conjugate Addition of Dialkylzinc Reagents to Acyclic Nitroalkenes:  A Catalytic Route to β²-Amino Acids, Aldehydes, and Alcohols

Abstract

Using chiral phosphoramidite ligand (S,R,R)-L1 in the conjugate addition to acyclic nitroalkenes for the first time, we obtained enantioselectivities up to 98%. The use of acyclic substrates with different dialkylzinc reagents provides a catalytic enantioselective route to (functionalized) beta2-amino aldehydes, acids, and alcohols.

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

“…At the same time, Feringa and co-workers 204 (Scheme 31(c)) applied the conjugate addition of dialkyl zinc reagents to nitropropene acetals using several chiral catalysts providing enantioselective reactions. In this case the best es values were also ob-SCHEME 29 Diastereo-and enantioselective hydrogenation for the preparation of a ␤-homothreonine derivative-a precursor of a key intermediate for carbapenem antibiotics production.…”

Cu‐ and Ni‐Catalyzed Conjugated Additions of Organozincs and Organoaluminums to α,β‐Unsaturated Carbonyl Compounds

“…The corresponding amino acid was obtained Following reduction, protection of the amino group, and hydrolysis (Scheme 2.40). The second report, from Feringa et al, relied on the conjugated addition to nitroacetals [174], although a greater generality of this approach was demonstrated by the addition of several different dialkylzincs to furnish the corresponding nitroacetals in high yields and enantioselectivity (88-98% ee) (Scheme 2.41). The use of nitroacetals also proved to be beneficial from a synthetic point of view, since a further elaboration of the aminoacetals, after reduction of the nitro group, gave rise to various chiral amino alcohols, amino aldehydes, or amino acids.…”

Enantioselective Radical Reactions

“…Several methods exist for the enantioselective synthesis of β-substituted β-amino acids (β 3 -amino acids); however, synthesis of α-substituted β-amino acids (β 2 -amino acids) is very limited [28,29]. A report on highly enantioselective hydrogen atom transfer reactions to synthesize β 2 -amino acids (Scheme 9) has recently been described [30].…”