STEREOCHEMISTRY OF BASE-CATALYZED ADDITION OF THIOPHENOL TO 3-H CARBACEPHALOSPORINS

The stereochemistry of thiophenol addition to 3-H carbacephalosparins by the Michael addition reaction has been determined utilizing various NMR techniques. Detailed coupling information along with nuclear Overhauser enhancement studies indicate the thioadducts 8a-e are formed by initial nucleophilic attack of the thiolate ion from the sterically more hindered beta-face of the six-membered ring followed by proton delivery from the same face. The kinetic product has a trans disposition of the phenylthio and ester substituents which initially occupy axial positions in a chairlike conformation of the six-membered ring. In addition, preliminary data suggest the kinetic product slowly interconverts to the thermodynamic product through an elimination-addition mechanism affording the isomer where the thiolate ion has formally added from the alpha-face.