Dualistic Reactivity of Lithium and Zinc Dienolates with Imines: Effects of Counterion, Temperature, and Substituents on α- and γ-Coupling

Article abstract of DOI:10.1021/jo00104a048

Lithium and zinc dienolates of 3-butenoic, 3-methyl-2-butenoic, 3-pentenoic, and 4-phenyl-3-butenoic methyl esters are reacted with imines R1C(H)=NR2 <3a: R1 = 2-pyridyl, R2 = Ph; 3b: R1 = Me3SiCC; R2 = Ph; 3c: R1 = 2-pyridyl, R2 = (R)-PhCH(CH3); 3d: R1 = Me3SiCC; R2 = (R)-PhCH(CH3)>.Depending on metal counterion, temperature, and substituents, the C-C coupling occurs either at the 2-position (α-coupling) or at the 4-position (γ-coupling) of the dienolate, giving β-amino esters and α,β-unsaturated esters, respectively.The α-coupling occurs at -78 deg C and is reversible, whereas γ-coupling products are formed upon warming to -20 deg C.The C-C coupled products may undergo irreversible ring closure to β-lactams (from β-amino esters) or 5,6-dihydropyridin-2-ones (from (Z)-α,β-unsaturated esters).Starting from enantiomerically pure imine 3c, high (71-92percent) asymmetric inductions were realized in both β-lactams and 5,6-dihydropyridin-2-ones; γ-coupling of enolate 2a and chiral imine 3d occurred with low diastereoselectivity (15percent).Four factors favor the formation of β-lactams: (i) the use of zinc dienolates, (ii) 4-substitution of the dienolates, (iii) nonaromatic imine N-substituents, and (iv) a low reaction temperature (-78 deg C).The product formation is discussed in terms of six-membered cyclic transition states, involving either zinc enolates (α-coupling) or isomeric allylzinc species (γ-coupling).