Diastereodivergent Synthesis of Bridged Tetrahydroisoquinoline Derivatives Catalyzed by Modularly Designed Organocatalysts

Abstract

AbstractThe diastereodivergent synthesis of bridged 1,2,3,4‐tetrahydroisoquinoline derivatives has been achieved by using appropriate modularly designed organocatalysts (MDOs) that are self‐assembled in situ from amino acids and cinchona alkaloid derivatives. The domino Mannich/aza‐Michael/aldol reaction between (E)‐2‐[2‐(3‐aryl‐3‐oxoprop‐1‐en‐1‐yl)phenyl]acetaldehydes and ethyl or benzyl (E)‐2‐[(4‐methoxyphenyl)imino]acetates catalyzed by MDOs gives two different diastereomers of the desired bridged tetrahydroisoquinolines in good yields and excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to >99% ee). The diastereodivergence was achieved in the aldol reaction step.magnified image