Studies on stereoselective [2+2] cycloadditions between N,N-dialkylhydrazones and ketenes.
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.
Martín-Zamora
Eloísa
E
Dpto. de Química Orgánica, Universidad de Sevilla, Spain.
Ferrete
Ana
A
Llera
José M
JM
Muñoz
Jesús M
JM
Pappalardo
Rafael R
RR
Fernández
Rosario
R
Lassaletta
José M
JM
D003198:Computer Simulation; D003500:Cyclization; D005030:Ethylenes / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D013237:Stereoisomerism
D005030:Ethylenes; D006835:Hydrazones; D007659:Ketones; C008223:ketene