Stereoselective Synthesis of β-4′-Hydroxymethyl-Deleted Nucleosides via CPA-Ph3PS Cooperative-Catalyzed Iodocyclization

β-4′-Hydroxymethyl-deleted nucleosides are a class of four-carbon-sugar isonucleosides that possess significant research value in medicinal chemistry and artificial genetic polymer science. Nevertheless, current synthetic methodologies are hampered by several drawbacks, including poor diastereoselectivity, considerable side-product formation, and lengthy synthetic sequences. Herein, we report a cooperative catalytic strategy combining chiral phosphoric acid (CPA) and the achiral sulfur-containing Lewis base triphenylphosphine sulfide (Ph3PS) for the stereoselective synthesis of β-4′-hydroxymethyl-deleted nucleosides via asymmetric alkene iodocyclization. Acting as a Brønsted acid, CPA anchors the hydroxyl nucleophilic site of the substrate through hydrogen-bonding interactions, whereas Ph3PS activates the iodine source. The two catalysts work in concert to modulate the spatial conformation of iodonium intermediates, enabling the hydroxyl nucleophile to attack the iodonium carbon from the α-face of the substrate and thus construct the β-N-glycosidic bond with high stereoselectivity. This iodocyclization reaction delivers a diastereomeric ratio up to 98:2 and an isolated yield of 95%, and it can be readily scaled up to gram-scale preparation. Featuring mild reaction conditions and efficient practicality, the present synthetic strategy provides a concise and efficient asymmetric route toward 4′-hydroxymethyl-deleted isonucleosides.