Stereocontrolled Synthesis of β‑Lactams within [2]Rotaxanes: Showcasing the Chemical Consequences of the Mechanical Bond

The intramolecular cyclization of N-benzyl­fumar­amide [2]­rotaxanes is described. The mechanical bond of these substrates activates this transformation to proceed in high yields and in a regio- and diastereo­selective manner, giving interlocked 3,4-disubstituted trans-azetidin-2-ones. This activati...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2016-07, Vol.138 (28), p.8726-8729
Main Authors: Martinez-Cuezva, Alberto, Lopez-Leonardo, Carmen, Bautista, Delia, Alajarin, Mateo, Berna, Jose
Format: Article
Language:English
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Summary:The intramolecular cyclization of N-benzyl­fumar­amide [2]­rotaxanes is described. The mechanical bond of these substrates activates this transformation to proceed in high yields and in a regio- and diastereo­selective manner, giving interlocked 3,4-disubstituted trans-azetidin-2-ones. This activation effect markedly differs from the more common shielding protection of threaded functions by the macrocycle, in this case promoting an unusual and disfavored 4-exo-trig ring closure. Kinetic and synthetic studies allowed us to delineate an advantageous approach toward β-lactams based on a two-step, one-pot protocol: an intramolecular ring closure followed by a thermally induced dethreading step. The advantages of carrying out this cyclization in the confined space of a benzylic amide macrocycle are attributed to its anchimeric assistance.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.6b05581