Acetal Substitution Reactions: Stereoelectronic Effects, Conformational Analysis, Reactivity vs Selectivity, and Neighboring-Group Participation

Acetal substitution reactions can proceed by a number of mechanisms, but oxocarbenium ion intermediates are involved in many of these reactions. Our research has focused on understanding the conformational preferences, structures, and reactions of these intermediates. This account summarizes our observations that electrostatic effects play a significant role in defining the preferred conformations, and that torsional effects determine how those intermediates react. Neighboring- group effects are not as straightforward as they might seem, considering that oxocarbenium ion intermediates are in equilibrium with structures that involve stabilization by a nearby substituent. 1 Introduction 2 Unexpected Stereoselectivities 3 Determining Conformational Preferences of Oxocarbenium Ions 4 Structures of Carbocations by NMR Spectroscopy and X-ray Crystallography 5 Stereoelectronic Models for Reactions Involving Other Oxocarbenium Ions 6 Stereoselectivity and Reactivity: When They Correlate, When They Do Not 7 Neighboring Group Participation Is Not as Simple as It Seems 8 What Is True for Carbocations Is True for Carbonyl Compounds 9 Stereoelectronic and Torsional Effects in Reactions of Enolates 10 Summary of Expected Selectivities for Reactions of Cyclic Acetals 11 Conclusion.