(3R)-Chiral Control of 3-Alkyl-3-hydroxy-beta-lactams via Addition Reaction of Imines to Enolates of 1,3-Dioxolan-4-ones.
A method is described for the chiral construction of (3R)-3-alkyl-3-hydroxy-beta-lactams in a versatile and predictable manner. This protocol follows Seebach's synthetic principle of self-regeneration of stereocenters and has been applied to addition reactions among a selected number of imines and (2S)-chiral enolates of 1,3-dioxolan-4-ones. These reagents are easily available from the acetalization of (S)-alpha-hydroxy acids (lactic, mandelic, isovaleric, malic) and pivalaldehyde or pinacolone. In several cases, the addition of the enolate to the imine, the cyclization, and the removal of the auxiliary center occur in a one-step sequence, affording the corresponding beta-lactams as (3R,4S)-Z and (3R,4R)-E diastereomeric mixtures with high enantiomeric excesses. Four N-unsubstituted (3R,4S)-3-hydroxy-3-methyl-beta-lactams bearing 2-furyl (4e), phenylethenyl (4h), methoxycarbonyl (4i), and 2-thienyl (4l) substituents at C4 were obtained as major diastereomers and were purified by crystallization. The simultaneous presence of these substituents at C3 and C4 make these beta-lactams useful intermediates for the synthesis of new taxoids with interesting structural modifications at the isoserine moiety.
Barbaro
Gaetano
G
CNR, Centro Studi Macromolecole Stereordinate ed Otticamente Attive, Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, I-56126 Pisa, Italy.
Battaglia
Arturo
A
Guerrini
Andrea
A
Bertucci
Carlo
C