Investigation Of The Stereoselectivity In The Staudinger Reaction

The reaction of ketene and imine [2+2] cycloaddition to yieldβ-lactam is called Staudinger reaction. This is to commemorate Geman chemist Hermann Staudinger first reported the reaction in 1907. Although Staudinger reaction was discovered more than 100 years, it was still one of the most important and useful method for the synthesis ofβ-lactams and their derivatives.β-Lactam is recognized as one of the most important class of compounds possessing a wide range of antibiotic activities. As the most valuable antibiotic, the design and synthesis of these compounds, and their stereochemical characteristics, has become one of the frontier fields in organic synthesis. In this paper, the structure, classification and synthetic methods ofβ-lactam are mentioned in brief. The research progesses inβ-lactams containing ferrocene moiety are summarized, as well as the significant applications of adamantane derivatives in biological and medical fields. On the basis of these, the ketene was generated by thermal Wolff rearrangement from diazo ketone, and then reacted with different substituted imines via the [2+2] cycloaddition reaction. The cis/trans ratios of theβ-lactam diastereoisomers were determined by 1H NMR spectra, and a series of trans-β-lactams were obtained as the major products. The stereoselectivity of the [2+2] cycloaddition has also been discussed. The main works are summarized as below.1. The reactions of ferrocenyl diazo ketone. Ferrocenyl diazo ketone 1a was reacted with five imines 2 via the [2+2] cycloaddition reaction, giving a series ofβ-lactam diastereoisomers 3a-e, with yields of 50-86%. The structures of 6 isolated compounds were determined by IR, 1H NMR, 13C NMR, MS and HRMS, partially by elemental analysis.2. The reactions of aryl diazo ketone. Three aryl diazo ketones 1b-d was reacted with imines 2 via the [2+2] cycloaddition reaction, giving a series ofβ-lactam diastereoisomers 3f-s, with yields of 36-83%. The structures of 17 isolated compounds were determined by IR, 1H NMR, partially unreported compounds by 13C NMR, MS and HRMS.3. The reactions of adamantyl diazo ketone. Adamantyl diazo ketone 1e was reacted with five imines 2 via the [2+2] cycloaddition reaction, yielding a series ofβ-lactam diastereoisomers 3t-x, with yields of 7-82%. The structures of 5 isolated compounds were determined by IR, 1H NMR, 13C NMR, MS and HRMS.4. By means of the analysis of the relative stereoselectivity (the cis/trans ratios) of these three series of reactions, the relationship between electronic effect or steric effect of the ketene and imine substituents and the stereochemical outcomes of the Staudinger reaction was discussed. These works provide a proof for controlling the stereoselectivity of the Staudinger reaction.