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Studies on Stereoselective [2+2] Cycloadditions between N,N‐Dialkylhydrazones and Ketenes
Author(s) -
MartínZamora Eloísa,
Ferrete Ana,
Llera José M.,
Muñoz Jesús M.,
Pappalardo Rafael R.,
Fernández Rosario,
Lassaletta José M.
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400452
Subject(s) - cycloaddition , chemistry , stereoselectivity , hydrazone , ketene , computational chemistry , stereochemistry , formaldehyde , ab initio , combinatorial chemistry , pericyclic reaction , organic chemistry , catalysis
Staudinger‐like cycloadditions between chiral, non‐racemic N,N‐dialkylhydrazones 1 and functionalized ketenes constitute an efficient methodology for the stereoselective construction of the β‐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 β‐amino‐α‐hydroxyacids (2 R ,3 S )‐phenylisoserine ( 42 ) and (2 R ,3 S )‐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.