Stereocontrolled Access to Carbocyclic Nucleosides Bearing Multiple Stereocenters via Desymmetrizing Hydroformylation.

Frameworks bearing multiple stereocenters are ubiquitous structural motifs in natural products, pharmaceuticals, and functional materials, yet the precise installation of multiple stereogenic centers in a single step remains a longstanding challenge. Conventional approaches typically require multistep sequences, resolution, or stoichiometric chiral auxiliaries. Here we describe a rhodium-catalyzed desymmetrizing hydroformylation of -cyclic olefins that enables the one-step construction of carbocyclic nucleoside scaffolds bearing up to five stereocenters with excellent diastereo- and enantiocontrol. The transformation exhibits broad generality, accommodating five- to seven-membered carbocycles as well as a range of heterocycles, thereby offering modular access to structurally diverse nucleoside analogues. Remarkably, the reaction operates efficiently at parts-per-million (ppm) catalyst loadings, delivering an unprecedented turnover number (TON) of 86,000─the highest value reported for asymmetric hydroformylation to date. With complete atom economy and operational simplicity, this method offers a broadly applicable platform for the stereocontrolled construction of complex carbocyclic nucleoside frameworks.