Origin of Stereoselectivity in S_E2′ Reactions of Six‐membered Ring Oxocarbenium Ions

Abstract Oxocarbenium ions are key reactive intermediates in organic chemistry. To generate a series of structure‐reactivity‐stereoselectivity principles for these species, we herein investigated the bimolecular electrophilic substitution reactions (S E 2′) between allyltrimethylsilane and a series of archetypal six‐membered ring oxocarbenium ions using a combined density functional theory (DFT) and coupled‐cluster theory approach. These reactions preferentially proceed following a reaction path where the oxocarbenium ion transforms from a half chair ( 3 H 4 or 4 H 3 ) to a chair conformation. The introduction of alkoxy substituents on six‐membered ring oxocarbenium ions, dramatically influences the conformational preference of the canonical 3 H 4 and 4 H 3 conformers, and thereby the stereochemical outcome of the S E 2′ reaction. In general, we find that the stereoselectivity in the reactions correlates to the “intrinsic preference” of the cations, as dictated by their shape. However, for the C5‐CH 2 OMe substituent, steric factors override the “intrinsic preference”, showing a more selective reaction than expected based on the shape of the ion. Our S E 2′ energetics correlate well with experimentally observed stereoselectivity, and the use of the activation strain model has enabled us to quantify important interactions and structural features that occur in the transition state of the reactions to precisely understand the relative energy barriers of the diastereotopic addition reactions. The fundamental mechanistic insight provided in this study will aid in understanding the reactivity of more complex glycosyl cations featuring multiple substituents and will facilitate our general understanding of glycosylation reactions.