Kinetic differences in the chlorination of cephalosporin versus carbacephalosporin enols: Evidence of sulfur neighboring group participation

Article abstract of DOI:10.1021/jo00098a034

Intermediates in the chlorination of carbacephalosporin and cephalosporin enols with chlorotriphenoxyphosphonium chloride, (PhO)₃P⁺Cl Cl^-, have been characterized at low temperatures by NMR. ³¹P NMR has been used to determine the rate constants and Arrhenius activation energies for the chlorination of the cephalosporin enol 1b and the carbacephalosporin enol 1c. The results show a 3.7 kcal/mol lower activation energy for the chlorination of the cephalosporin enol. Semiempirical and ab initio calculations have been employed to evaluate chloride attack and phosphate departure for model cephalosporin and carbacephalosporin enols. The experimental and computational results are consistent with a chlorination mechanism that involves rapid, reversible chloride addition to an intermediate enol phosphonium species followed by rate-limiting phosphate departure. The lower activation energy for phosphate departure in the cephalosporin case is attributed to sulfur neighboring group participation.