Stereoselective synthesis of bicyclic tetrahydrofuran-fused β-lactams and their conversion into methyl cis-3-aminotetrahydrofuran-2-carboxylates

cis-3-Benzyloxy-4-(2-mesyloxyethyl)azetidin-2-ones were shown to be useful starting products for the synthesis of cis-2-oxa-6-azabicyclo[3.2.0]heptan-7-ones in high overall yields and purity upon hydrogenolysis of the benzyl ether substituent followed by intramolecular nucleophilic substitution using sodium hydride in THF. These unconventionally C-fused bicyclic β-lactams were easily converted into the corresponding methyl cis-3-aminotetrahydrofuran-2-carboxylates via acidic methanolysis. This methodology constitutes a convenient alternative for the known preparation of cis-4,4-dimethyl-2-oxa-6-azabicyclo[3.2.0]heptan-7-ones and methyl cis-3-amino-4,4-dimethyltetrahydrofuran-2-carboxylates, as their 4,4-nor-dimethyl variants are usually considered to be more promising compounds within the field of drug design.