Efficient Solvent‐Free Robinson Annulation Protocols for the Highly Enantioselective Synthesis of the Wieland–Miescher Ketone and Analogues

A highly efficient (93% overall yield) and enantioselective (94% ee ) synthesis of the Wieland–Miescher ketone (10‐g scale) through a solvent‐free Robinson annulation procedure is reported. The process involves only 1 mol% triethylamine as the base in the initial Michael process and the organocatalyst N ‐tosyl‐( S a )‐binam‐ L ‐prolinamide (2 mol%) and benzoic acid (0.5 mol%) for the intramolecular aldol process. This green protocol is applied to a wide range of valuable building block analogues of the Wieland–Miescher ketone (10 examples). Among these, a noteworthy compound for terpene synthesis is the 8a‐allyl derivative, which is prepared in 93% yield and 97% ee in a process allowing the recovery and reutilization of the organocatalyst. Furthermore, a one‐pot, two‐step process has also been developed.