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 meso-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.
Ren et al. (2026) studied this question.