The influence of nucleophile reactivities on stereoselectivities in the substitutions of acetals and the associated mechanistic implications

This dissertation describes our investigations into nucleophilic substitutions of acetals that deviate from SN1 stereoelectronic models. When weak nucleophiles are employed in these transformations, stereoselectivities conform to known SN1 stereoelectronic models. In contrast, stereoselectivities in the substitutions of acetals with strong nucleophiles depend on reaction conditions. When coordinating groups are present, SN2-like pathways become predominant. In the majority of cases examined, the major stereoisomers formed from reactions that proceed through SN2-like pathways were opposite to the major stereoisomers formed from analogous reactions that proceed through SN1 pathways. In the absence of coordinating groups, however, erosions in selectivities were observed when strong nucleophiles were employed. These erosions in selectivities are attributed to rates of nucleophilic additions to oxocarbenium ion intermediates that approach the diffusion limit.