DEVELOPMENT OF DOMINO AND STEREOCONVERGENT REACTIONS FOR THE ASSEMBLY OF STEREOCHEMICALLY COMPLEX ORGANIC SCAFFOLDS

The stereochemical complexity of small molecules of biological interest has steadily increased across recent decades and has therefore inspired continued interest in reaction platforms which rapidly assemble complex organic scaffolds. Herein, we demonstrate that domino reactions - including organocatalyzed Michael-aldol reactions and oxidation-spirolactonization-oxidation sequences of β-furyl amides - can rapidly build stereochemically complex products from simple starting materials. Stereoconvergency of β-dicarbonyls is employed for the assembly of products with up to five contiguous stereocenters in a one-pot fashion. Mechanistic investigations including in situ 1H NMR spectroscopy and reaction progress studies elucidate key reaction intermediates and the origins of stereoconvergence.