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

Article abstract of DOI:10.1021/jo991932s

4-Alkenyl-2-azetidinone systems were converted to the corresponding ethyl 2-[4-alkenyl-2-oxo-1azetidinyl]-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]-azetidin2-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]₂-Mo(=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.^2,50^8,12]tetradec-13-ene-1-carboxylate (19).