Asymmetric synthesis of β-lactams by [2+2] cycloaddition using 1,4:3,6-dianhydro-D-glucitol (isosorbide) derived chiral pools

Highly diastereoselective synthesis of cis-beta-lactams via [2+2] cycloaddition reactions of imines derived from a chiral bicyclic aldehyde and ketenes is described. The chiral bicyclic aldehyde as well as chiral acids were prepared from commercially available inexpensive isosorbide. The cycloaddition reaction was found to be highly diastereoselective; in some cases giving a single diastereomer of cis-azetidin-2one in very good yields. A moderate diastereoselectivity was observed with chiral ketenes derived from isosorbide. (c) 2007 Elsevier Ltd. All rights reserved.