Stereoselective Higher‐Order [10+4]‐ and [10+6] Cycloadditions Between Two Highly Unsaturated and Ambiphilic π‐Addends

A fundamental challenge in higher-order cycloadditions (HOCs) is to control multiple layers of selectivity-peri-, regio-, diastereo-, and enantioselectivity. Controlling these selectivities in HOCs is very challenging when they involve two highly unsaturated and ambiphilic π-addends. Here, we study this complexity in enantioselective aminocatalyzed HOCs between isobenzofulvenes, reacting as 10π-components, and 3-oxidopyridinium betaines, reacting as 4π- or 6π-components. The reaction generates three different products: an allowed [10+4] cycloadduct and two forbidden regioisomeric [10+6] cycloadducts. For the [10+6] reaction pathway, the 3-oxidopyridinium betaine reacts as a 6π-component with the fulvene scaffold in unprecedented cycloadditions. The outcome of these cycloadditions exhibits the challenge in controlling the peri- and regioselectivity in complex HOCs involving two highly unsaturated and ambiphilic π-addends. We demonstrate that it is possible to optimize the cycloadditions toward the selective formation of the [10+4] cycloadduct or the [10+6] cycloadducts. Experimental investigations were conducted in combination with DFT calculations, in order to elucidate the origins of these selectivities.