A Stereoelectronic Model To Explain the Highly Stereoselective Reactions of Nucleophiles with Five-Membered-Ring Oxocarbenium Ions

Abstract

To date, no general stereoelectronic model has been offered to explain stereoselective reactions of five-membered-ring oxocarbenium and iminium ions. In contrast, the model used to understand the stereoselectivity of nucleophilic attack upon sixmembered-ring cations is a powerful predictive tool used widely by synthetic organic chemists.1,2 Because of the importance of five-membered-ring oxocarbenium ions as reactive intermediates in bioorganic3 and synthetic organic chemistry,4-6 a model that would provide insight regarding their reactivities would be an invaluable complement to the current understanding of stereoselective reactions. In this paper, we present a general stereoelectronic model (the “inside attack” model) to explain the stereoselective reactions of five-membered-ring oxocarbenium ions. Previous models employed to explain stereoselective reactions of five-membered-ring oxocarbenium ions do not encompass a wide range of substrates, nucleophiles, and conditions. The most advanced model was proposed by Reissig based upon a systematic study of reactions of monomethyl γ-lactols.7,8 This model, however, has limitations. For example, the stereoselective nucleophilic substitutions of carbon nucleophiles onto D-ribose acetals such as 1 (eq 1), reactions for which oxocarbenium ion