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.
Faghtmann et al. (Thu,) studied this question.