Turning Enantiomeric Relationships into Diastereomeric Ones: Self-Resolving α-Ureidophosphonates and Their Organocatalytic Enantioselective Synthesis
Vanda Dašková, Damián Padín, Ben L. Feringa
Abstract
Controlling chiral recognition and chiral information transfer has major implications in areas ranging from drug design and asymmetric catalysis to supra- and macromolecular chemistry. Especially intriguing are phenomena associated with chiral self-recognition. The design of systems that show self-induced recognition of enantiomers, i.e., involving homochiral versus heterochiral dimers, is particularly challenging. Here, we report the chiral self-recognition of α-ureidophosphonates and its application as both a powerful analytical tool for enantiomeric ratio determination by NMR and as a convenient way to increase their enantiomeric purity by simple achiral column chromatography or fractional precipitation. A combination of NMR, X-ray, and DFT studies indicates that the formation of homo- and heterochiral dimers involving self-complementary intermolecular hydrogen bonds is responsible for their self-resolving properties. It is also shown that these often unnoticed chiral recognition phenomena can facilitate the stereochemical analysis during the development of new asymmetric transformations. As a proof of concept, the enantioselective organocatalytic hydrophosphonylation of alkylidene ureas toward self-resolving α-ureidophosphonates is presented, which also led us to the discovery of the largest family of self-resolving compounds reported to date.