Cycloadditions of Ketenes Generated in the Wolff Rearrangement. Stereoselective Synthesis of Aminoalkyl-Substituted β-Lactams from α-Amino Acids

• Published in: Journal of organic chemistry Vol. 62; no. 17; pp. 5873 - 5883
• Main Authors: Podlech, Joachim, Linder, Michael R
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 22.08.1997; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ORGANIC-SYNTHESIS; ANTIBIOTICS; ASYMMETRIC-SYNTHESIS; SCOPE; CHROMIUM CARBENE COMPLEXES; ARNDT-EISTERT REACTION; ESTERS; INTERMEDIATE; ENOLATE IMINE CONDENSATION; PHOTOLYTIC REACTION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9705069

Diazo ketones 1−16, derived from suitable protected amino acids (Ala, Leu, Val, Ile, Tle, Phe, Pro, Orn, Lys, Ser, and Thr), have been photochemically rearranged, leading to the corresponding ketene intermediates. They were trapped with N-benzylbenzaldimine 17 to give β-lactams 18−33 in up to 90% yield. In these cycloadditions, two of the four possible diastereoisomers were formed exclusively. The selectivity ranged from 60:40 to 93:7 and the bulkiness of the parent amino acid side chain is the governing factor. The relative configuration was proved by three X-ray crystal structures. The diastereoselectivity in these reactions is also influenced by the use of chiral N-phenethylbenzaldimines 34 and 35. With regard to a projected deprotection of the lactam-nitrogen, N-allyl- (49) and N-(p-methoxybenzyl)benzaldimine (44) were used in this reaction. This led to the N-allyl β-lactams 50 and 51 in 62 and 56% yield, respectively, and to the p-methoxybenzyl-substituted β-lactams 45 and 46 (50 and 72% yield). The p-methoxybenzyl group on the valine-derived β-lactam 45a can be cleaved with potassium peroxodisulfate in 63% yield.