Tandem Ireland−Claisen Rearrangement Ring-Closing Alkene Metathesis in the Construction of Bicyclic β-Lactam Carboxylic Esters

4-Alkenyl-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 β-lactam dienes via sequential N-alkylation, Ireland−Claisen ester enolate rearrangement and esterification. Ring-closing metathesis using the Schrock [(CF3)2MeCO]2Mo(CHCMe2Ph)(NC6H3-2,6-iso-Pr2) (1) or Grubbs Cl2(Cy3P)2Ru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[5.2.0]nona-2,4-diene-2-carboxylate (18), a novel type of bicyclic β-lactam. Diels−Alder cycloaddition further afforded tetracyclic systems exemplified by tert-butyl (1R,4S,5R,7S)-4-[(1R)-1-hydroxyethyl]-3,9,11-trioxo-10-phenyl-2,8,10,12-tetraazatetracyclo[5.5.2.0.2,508,12]tetradec-13-ene-1-carboxylate (19).