Browsing by Subject "cyclization"

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    Stereocontrol in the Synthesis of β-Lactams Arising from the Interlocked Structure of Benzylfumaramide-Based Hydrogen-Bonded [2]Rotaxanes
    (Thieme, 2019-01-18) Martinez-Cuezva, Alberto; Lopez-Leonardo, Carmen; Alajarín, Mateo; Berná Cánovas, José; Química Orgánica
    β-Lactams are highly valuable compounds due to their antibiotic activity. Among the number of well-established methodologies for building this privileged scaffold, our research group has settled on a novel synthetic approach for their preparation. This Account focuses on our latest progress in the synthesis of these compounds through a novel base-promoted intramolecular cyclization of benzylfumaramide-based rotaxanes. The mechanical bond plays a significant role in the process by activating the cyclization inside the macrocycle void, avoiding the formation of byproducts and fully controlling the diastereoselectivity. Further investigations on this transformation led to the formation of ­enantioenriched 2-azetidinones. The cyclization of enantiopure interlocked α-methylbenzylfumaramides allows the formation of two new stereogenic centers in the lactamic four-membered ring, one of them a quaternary carbon, keeping the initial configuration of the chiral group of the starting material.
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    Stereocontrolled synthesis of -lactams within [2]rotaxanes: a showcase of the chemical consequences of the mechanical bonding
    (ACS, 2016-06-29) Martinez-Cuezva, Alberto; Lopez-Leonardo, Carmen; Bautista, Delia; Alajarín, Mateo; Berná Cánovas, José; Química Orgánica
    The intramolecular cyclization of N-benzyl fumaramide [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 differs from the common shielding stabilization of threaded functions through amide-based macrocycles promoting an unusual and disfavored 4-exo-trig ring closure. Further kinetic and synthetic studies allowed us to produce an original approach towards  -lactams through a one-pot protocol based on an intramolecular ring closure followed by a thermally-induced dethreading step. The advantages for carrying out this cyclization in the confined space of a benzylic amide macrocycle were attributed to the anchimeric assistance of the surrounding macrocycle.