Organocatalytic Enantioselective [4 + 4] Cycloadditions of Furan <i>Ortho</i>‐Quinodimethanes

Abstract The enantioselective [4 + 4] cycloaddition for the construction of cyclooctanoids is a challenging transformation in organic chemistry. Herein, we present the first organocatalytic enantioselective [4 + 4] cycloaddition of furan ortho ‐quinodimethanes, activated by dearomatization of the heteroaromatic compound, which thereby allows for the cycloaddition with dienes. The [4 + 4] cycloaddition is catalyzed by a quinine‐derived primary amine in combination with a chiral phosphoric acid and a carboxylic acid affording cyclooctanoids isolated as a single diastereoisomer in good yields and with up to 94% ee . This reaction concept allows for the formation of cyclooctanoids without benzofusion, as demonstrated by oxidative opening of the furan ring. Computational studies of the reaction mechanism for the [4 + 4] cycloaddition point to a stepwise process. Surprisingly, the stereochemical outcome of the reaction is attributed to protonation of the two organocatalyst‐bound cyclooctanoid intermediates leading to a preferred set‐up for catalyst elimination to account for the absolute configuration of the cyclooctanoid.