On the relationships between 18O-transfer, diastereotopic selectivity, and asymmetric induction in an intramolecular Pummerer reaction

The cyclization of benzyl 2-carboxyphenyl sulfoxide (1) to 2-benzylbenzoxathiane-6-one (2) has been examined by a combination of 18O-labelling of the sulfoxide oxygen, stereoselective deuterium labelling in the benzylic position, and the use of optically active compounds. With dicyclohexylcarbodiimide (DCC) as the cyclizing agent, the reaction proceeds with 55.8% retention of the sulfoxide oxygen, 57.8% preference for abstraction of one of the diastereotopic methylene protons, and it produces a 61.4/38.6 mixture of enantiomers. It is proposed that all three experimental observables are controlled by the competition between initial attack of the DCC upon the sulfoxide oxygen and upon the carboxyl group, and a mechanism is proposed for the reaction which clarifies the relationship between these observables. In agreement with earlier work by Stridsberg and Allenmark, DCC affords 2 having the opposite sign of rotation from 1, and acetic anhydride affords 2 having the same sign of rotation as 1. Asymmetric induction in the latter reaction is significantly less than with DCC because of competing epimerization at sulfur, but the origin of the differences in the sign of rotation of 2 under the different conditions has been clarified by the finding that there is less than 40% retention of the sulfoxide oxygen with acetic anhydride as the reagent.