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

ABSTRACT 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.