Diastereoselective ring expansion of beta-lactams toward gamma-lactams via N-acyliminium intermediates.
[reaction: see text] The diastereoselective synthesis of highly functionalized gamma-lactams starting from 4-(1-bromoalkyl)-2-azetidinones via N-acyliminium intermediates is described. The carbenium ions, formed by dissociation of bromide from 4-(1-bromoalkyl)-2-azetidinones in polar medium, are converted via a ring expansion toward N-acyliminium ions, which are susceptible to attack of oxygen, nitrogen, and carbon nucleophiles. In this way, a variety of 5-hydroxy-, 5-alkoxy, 5-cyano-, 5-allylamino- and 5-azido-4,4-dimethyl-2-pyrrolidinones were synthesized. It was found that dehydrobromination of 4-(1-bromoalkyl)-2-azetidinones constituted an important side reaction when the title reactions were carried out in DMSO. When THF was used as a solvent, generally no dehydrobromination was observed, implying that higher yields of gamma-lactams were obtained in THF compared to reactions performed in DMSO. Also substituents of the 4-(1-bromoalkyl)-2-azetidinones play an important role concerning the obtained diastereoselectivity and the degree of dehydrobromination.
Van Brabandt
Willem
W
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, B-9000 Ghent, Belgium.
De Kimpe
Norbert
N