De novo synthesis of threofuranoses via a triple-carbonylation cascade of aldehydes.

Carbohydrate synthesis is fundamental for developing therapeutics and probing biological systems, yet constructing complex sugars directly from simple aldehydes remains a formidable challenge. Iterative carbonylation strategies for establishing a synthetic blueprint toward stereochemically defined sugars have remained elusive due to cumulative catalyst deactivation and stereochemical drift. Here we report a rhodium-catalysed triple-carbonylation cascade that overcomes this limitation, converting diverse aldehydes into structurally defined 4-carbothreofuranoses in one step. Precise silane stoichiometry and ligand selection enforce kinetic synchronization of three CO insertions, terminated by silicon-directed cyclization. A chelation-relay mechanism propagates stereochemistry across three contiguous centres with good diastereocontrol. The method accommodates diverse substrates spanning aromatics to steroidal aldehydes. Synthetic utility is demonstrated through transformations enabling rapid access to N-/C-glycosides, nitrogen heterocycles and polyol motifs relevant to pharmaceutical applications. This work establishes carbonylative cascades as a platform for oxygen-rich scaffold assembly, bypassing classical protection-deprotection sequences in carbohydrate synthesis.