Cobalt carbonyl-catalyzed carbonylation of functionalized aziridines to versatile β-lactam building blocks

Abstract

The Co(CO)-catalyzed carbonylation of different classes of non-activated aziridines with diverse substitution patterns was investigated. Special attention was devoted to selectivity issues and reaction optimization. This study resulted in the regio- and stereospecific synthesis of 24 novel β-lactam target structures in high yields on a multigram scale. The synthetic potential of the newly obtained azetidin-2-ones was illustrated via ring-expansion, ring-closure, and/or side chain-functionalization protocols to provide a straightforward entry to novel pyrrolidines, C-fused bi- and tricyclic β-lactams and monocyclic carbapenem analogs.

One-Pot Construction of Diverse β-Lactam Scaffolds via the Green Oxidation of Amines and Its Application to the Diastereoselective Synthesis of β-Amino Acids

“…Although various methods have been reported for the construction of β-lactam rings (including transition-metal-catalyzed reactions, carbonylations, and enolate-imine condensations), − Staudinger cycloaddition, which is a formal [2 + 2] cycloaddition of an imine and a ketene, is the most versatile method for fabricating β-lactam rings (eq ). This method requires highly pure imines, which are generally susceptible to hydrolysis.…”

Synthesis of 3-Amino-4-substituted Monocyclic ß-Lactams—Important Structural Motifs in Medicinal Chemistry

“…Various other cyclizations involving N1-C2, C3-C4, and N1-C4 ring closures have also been reported [ 19 , 24 ]. In addition, there are also other less commonly used procedures, such as CO insertion [3+1] on aziridine ring, Ugi four-component reactions, and diiodomethane additions to amide dianions [ 25 , 26 ]. The most widely used protocols are based on either Mitsunobu-mediated cyclization of α-hydroxy-ß-amino acid hydroxamates ( Figure 1 , reaction B), or bromine-induced cyclization of γ,δ-unsaturated hydroxamates ( Figure 1 , reaction C).…”

Chemodiscrimination of Olefin Bonds Through Cross‐Metathesis Reactions – Synthesis of Functionalized β‐Lactam and β‐Amino Acid Derivatives

“…applications of functionalized -lactams [25][26][27][28][29][30][31][32] or some fused bicyclic -lactams. [33][34][35][36][37][38][39] For example, opening of the azetidinone ring of various -lactam derivatives is considered to be one of the most convenient pathways for the stereocontrolled synthesis of open-chain or cyclic 2,3 -amino acid derivatives.…”

“…They are useful starting materials for further synthetic transformations and used for the preparation of a set of valuable molecular systems such as amino acids, alkaloids, amino alcohols or heterocycles . The high synthetic value of this type of derivatives is demonstrated by the syntheses and applications of functionalized β‐lactams or some fused bicyclic β‐lactams . For example, opening of the azetidinone ring of various β‐lactam derivatives is considered to be one of the most convenient pathways for the stereocontrolled synthesis of open‐chain or cyclic β 2,3 ‐amino acid derivatives .…”