Chiral spiro-β-lactams from 6-diazopenicillanates

Abstract: Chiral spiro-β-lactam derivatives have been prepared via stereoselective 1,3-dipolar cycloaddition of 6-diazopenicillanates. Using dipolarophiles such as acrylonitrile, acrylates or methyl vinyl ketone spiro-2-pyrazoline-β-lactams were obtained, whereas the cycloaddition with N-substituted-maleimides afforded spiro-1-pyrazoline-β-lactams. 6-Diazopenicillanates also reacted with electron-deficient alkynes to give the corresponding spiro-3H-pyrazole-β-lactam as single product. The observed stereoselectivity can be explained considering that the major product results from the addition to the less sterically hindered α-side of the β-lactam. Microwave-induced denitrogenation of spiro-1-pyrazoline-β-lactams allowed the stereoselective synthesis of novel spirocyclopropyl-β-lactams. The rationalization of the observed selectivity was supported by electronic structure calculations. [Copyright &y& Elsevier]