Organocascade Synthesis of Bicyclo[3.3.1]nonan‐9‐ones Initiated by an Unusual 1,6‐Addition of Cyclohexanones to (E)‐2‐(3‐Arylallylidene)‐1H‐indene‐1,3(2H)‐diones

Abstract

AbstractAn efficient organocatalytic cascade reaction for the synthesis of the bicyclo[3.3.1]nonan‐9‐one skeleton is reported. The cascade reaction proceeds smoothly between prochiral 4‐substituted cyclohexanones and (E)‐2‐(3‐arylallylidene)‐indene‐1,3‐diones involving a 1,6‐/γ‐protonation/1,4‐addition sequence to construct bicyclic products that contain five stereogenic centers in good to high chemical yields and excellent diastereo‐ and enantioselectivity (up to >20:1 dr and 97% ee) in the presence of a thioether‐linked l‐prolinol‐camphor‐derived organocatalyst at ambient temperature. An interesting organocatalytic three‐component triple cascade reaction has been performed to produce a bicyclo[2.2.2]octan‐2‐one in a favorable chemical yield and stereoselectivity (>19:1 dr and 97% ee) starting from 1,3‐indanedione, an enal, and cyclohexenone in the presence of a primary amine organocatalyst.magnified image