Stereoselectivity in the synthesis of 2-azetidinones from ketenes and imines via the Staudinger reaction

Abstract

The 2-azetidinone (β-lactam) group is a crucial structural feature of one class of significant antibiotics. Its stereochemistry is very important to their biological activities. Stereoselectivity is one of the important issues in the synthesis of 2-azetidines from ketenes and imines via the Staudinger reaction. The origin of the diastereoselectivity in the reaction and influences of reaction conditions on the diastereoselectivity are reviewed. This will provide useful information for understanding and controlling the diastereoselectivity in the preparation of structurally defined 2-azetidinone derivatives.

Impact of Microwaves on Organic Synthesis and Strategies toward Flow Processes and Scaling Up

“…The Wolff–Staudinger reaction affords the formation of β-lactams via the [2 + 2] cycloaddition of ketenes with imines. The diastereoselectivity for the trans-substituted reaction has been studied in MW batch mode 104 as well as under continuous MW operation. 105 Because the protocol is considered problematic due to the release of gaseous nitrogen and in view of the high temperature, continuous MW mode is an appealing alternative to the batch synthesis.…”

Facile synthesis of novel monocyclic trans- and cis-3-oxo/thio/seleno-4-pyrazolyl-β-lactams

“…[48][49][50] In the present work, all the 2-benzyl/phenylthio/seleno ethanoic acids (Moore ketenes having S/Se-alkyl or aryl groups) on treatment with pyrazolyl substituted imines gives trans-β-lactams as suggested in the literature. [48][49][50] Whereas, the Bose-Evans ketenes (having O-alkyl or O-aryl groups) should give cis-β-lactams, which have been achieved in the synthesis of cis-3-methoxy/acetoxy-β-lactams with low yield. However, this cycloaddition did not afford the targeted products at lower temperature, therefore high temperature selectively favors the formation of predominantly trans-β-lactams.…”

“…Further, competition between the rate of isomerisation and direct ring closure, temperature and substituents plays an important role towards the stereoselectivity of these Staudinger cycloadditions which is well documented in literature. 39,[48][49][50] The crystal structure of trans-1-(4′-methoxyphenyl)-3-methoxy-4-(5′-chloro-3′-methyl-1′-phenyl-1H-pyrazol-4′-yl)azetidin-2-one 5p was established by X-ray crystallographic analysis (Figure 1). 45 It was crystallized from dichloromethane-hexane (3:1) as a colorless crystalline solid suitable for single crystal X-ray diffraction.…”

Synthesis and In Vitro Antiprotozoan Evaluation of 4-/8-Aminoquinoline-based Lactams and Tetrazoles

“…The Staudinger reaction of the Schiff-bases with the methoxy acetyl chloride exclusively furnished the cis β-lactam products ( 4a – g ) in 4–30% yields and over 90% purity except for 4f that still contained starting Schiff base traces even after extensive purification. The cis configuration was assigned based on the 1 H NMR model proposed by Xu and coworkers [ 34 , 35 ]. According to the model, when the J -coupling constant between the two protons on the adjacent chiral carbons of the β-lactam ring is between 4 and 6 ppm, then the configuration is cis , while between 2 and 3 ppm indicates trans .…”