Tandem Ireland-Claisen rearrangement ring-closing alkene metathesis in the construction of bicyclic β-lactam carboxylic esters

4-Alkeny-2-azetidinone systems were converted to the corresponding ethyl 2-[4-alkenyl-2-oxo-1-azetidinyl]-4-pentenoates. In addition, 4-(2-propenyl-1-oxy)-, 4-(2-propenyl-1-thio)-, 4-[N-(2-propenyl)-(4-toluenesulfonyl)]- and (3S,4R)-4-(2-propenyl)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-azetidin-2-one were converted into beta-lactam dienes via sequential N-alkylation, Ireland-Claisen ester enolate rearrangement and esterification. Ring-closing metathesis using the Schrock [(CF3)(2)MeCPO](2)Mo(=CHCMe2Ph)(=NC6H3-2,6-iso-Pr-2) (1) or Grubbs Cl-2(Cy3P)(2)Ru=CHPh (2) carbenes gave a series of [5.2.0] and [6.2.0] bicycles. Subsequent elaboration of the analogous (2R*,7R,8S)-tert-butyl 8-[(1R)( tert-butyldimethylsilyloxy)ethyl]-1-aza-9-oxobicyclo[5.2.0]non-4-ene-2-carboxylate (15), via selenation and desilylation, gave (+)-(2S,7R,8S)-tert-butyl 8-[(1R)-hydroxyethyl]-1-aza-9-oxobicyclo nona-2,4-diene-2-carboxylate (18), a novel type of bicyclic B-lactam. Diels-Alder cycloaddition further afforded tetracyclic systems exemplified by tert-butyl (1R,4S,5R,7S)-4-[(1R)-1-hydroxyethyl]-3, 11-trioxo-10-phenyl-2,8,10,12-tetraazatetracyclo[5.5.2.0(2,5)0(8,12)]tetradec-13-ene-1-carboxylate (19).