Recent Progress in Catalytic Asymmetric Pictet-Spengler Reaction to Construct 1,1-Disubstituted Scaffolds

1,1-disubstituted tetrahydroisoquinolines (THIQs) and tetrahydro-β-carbolines (THBCs) are key intermediates in the synthesis of various alkaloid natural products. These 1,1-disubstituted scaffolds are typically constructed via the Pictet-Spengler reaction. The asymmetric catalytic variant of this reaction enables access to stereochemically pure compounds with significant biological properties. This review focuses on recent progress in organocatalyzed and enzyme-catalyzed asymmetric Pictet-Spengler reactions to generate these 1,1-disubstituted motifs. 1 Introduction 2 Construction of 1,1-Disubstituted Tetrahydroisoquinoline (THIQ) Motif 3 Construction of 1,1-Disubstituted Tetrahydro-β-carboline (THBC) Motif 3.1 Enantioselective Pictet-Spengler Reactions 3.2 Diastereoselective Pictet-Spengler Reactions 4 Miscellaneous 5 Conclusion

Publikationsverlauf

Eingereicht: 14. November 2025

Angenommen nach Revision: 26. Dezember 2025

Accepted Manuscript online:
29. Dezember 2025