title: Studies on stereoselective [2+2] cycloadditions between N,N-dialkylhydrazones and ketenes.
abstract: Staudinger-like cycloadditions between chiral, non-racemic N,N-dialkylhydrazones 1 and functionalized ketenes constitute an efficient methodology for the stereoselective construction of the beta-lactam ring. The potential for fine tuning of the dialkylamino auxiliary structure, the availability of a high-yielding deprotection method for the release of the free azetidinones, and the high thermal and chemical stability of hydrazones as N-dialkylamino imines are highlighted as the key elements for the success of the strategy. This last aspect is of particular importance concerning generality: even hydrazones from easily enolizable aldehydes or from formaldehyde reacted to afford the corresponding cycloadducts with high chemical and stereochemical yields. The syntheses of the beta-amino-alpha-hydroxyacids (2R,3S)-phenylisoserine (42) and (2R,3S)-norstatin (45) were accomplished as illustrative examples of the synthetic utility of this procedure. A model system for the cycloaddition of g series auxiliaries was studied by ab initio computational methods. The collected results support a two-step mechanism through zwitterionic intermediates, and explain the observed absolute and relative stereochemistry in terms of the preferred outward cycloaddition to the Re face of the hydrazone.
authors.affiliation: Dpto. de Química Orgánica, Universidad de Sevilla, Spain.
authors.forename: Eloísa
authors.initials: E
authors.lastname: Martín-Zamora
authors.forename: Ana
authors.initials: A
authors.lastname: Ferrete
authors.forename: José M
authors.initials: JM
authors.lastname: Llera
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Muñoz
authors.forename: Rafael R
authors.initials: RR
authors.lastname: Pappalardo
authors.forename: Rosario
authors.initials: R
authors.lastname: Fernández
authors.forename: José M
authors.initials: JM
authors.lastname: Lassaletta
mesh_terms: D003198:Computer Simulation; D003500:Cyclization; D005030:Ethylenes / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D013237:Stereoisomerism
chemical_list: D005030:Ethylenes; D006835:Hydrazones; D007659:Ketones; C008223:ketene