Expanding the Scope of Primary Amine Catalysis: Stereoselective Synthesis of Indanedione-Fused 2,6-Disubstituted <i>trans-</i>Spirocyclohexanones

A cinchona-alkaloid-derived chiral primary-amine-catalyzed enantioselective method for the synthesis of the thermodynamically less stable indanedione-fused 2,6-<i>trans</i>-disubstituted spirocyclohexanones is demonstrated. Both the enantiomeric forms of the <i>trans</i> isomer are obtained in excellent yields and enantioselectivities. Furthermore, one of the enantiopure <i>trans</i>-spiranes bearing an additional α-substitution on the cyclohexanone ring was then epimerized into its thermodynamically stable <i>cis</i> counterpart, with little loss of enantioselectivity to demonstrate the feasibility of such a transformation. Mechanistic investigations revealed two competing pathways, a concerted Diels–Alder reaction and a stepwise Michael addition, for the formation of corresponding products