Amphiphilic bile acid-amino acid conjugates as sustainable organocatalysts for aqueous asymmetric aldol reactions: From molecular design to aggregation-controlled selectivity

Abstract

The amine-catalyzed aldol reaction has become a stable of organic synthesis with numerous applications affording predominantly the anti aldol product. Using our synthesized and characterized bile acid-amino acid conjugates with l-proline and l-phenylalanine, and bile acids amino derivatives we successfully performed regioselective aldol reactions in aqueous media controllably giving either the anti or syn diastereomer. These novel derivatives exhibited high catalytic activity, with the l-proline-based organocatalyst showing the highest efficiency, achieving yields up to 99 %, high diastereoselectivity for the anti product and moderate enantioselectivity. The l-phenylalanine-based one demonstrated good catalytic performance, achieving yields up to 99 % and good diastereoselectivity for the syn product. The environmental sustainability of these catalytic systems was further enhanced in the use of bio-based surfactants-amino acids conjugates utilizing water as the reaction medium, without the addition of any cosolvent, while aligning with the modern ethics of environmentally friendly practices. These findings reveal the potential application of natural bile acids scaffolds as versatile and eco-friendly conjugates to afford highly efficiency in sustainable organocatalysis for successfully achieving organic transformations in aqueous environments.