Although C(sp3)-C(sp3) bond-forming cross-coupling methods have become more common, stereocontrolled bond formation remains a challenge1, despite its importance for drug discovery, where there is a emerging demand for molecules with increased sp3 character2-4. Enantiospecific cross-coupling approaches would complement advances in enantioselective coupling5-8, but have been limited to specialized substrates with lower availability5,9 because stereospecific oxidative addition of more abundant chiral alkyl electrophiles is unknown10. Inspired by the classic, stereoretentive Curtius rearrangement11, here we disclose a catalytic strategy that proceeds by an analogous stereoretentive decarbonylation step to form a versatile chiral alkylnickel intermediate from easily available chiral amino acid and α-hydroxy-acid derivatives. The chiral alkylnickel intermediates decompose and/or racemize on the order of minutes, but are sufficiently stable to enable stereoretentive cross-electrophile coupling12 with alkyl radicals (derived from alkyl iodides) at relatively low temperature (22-40 °C). This mechanistic strategy provides a straightforward approach to stereocontrolled C(sp3)-C(sp3) bond formation, including diastereomers that are inaccessible by stereoselective radical mechanisms. The 'metallo-Curtius' strategy described in this study lays a mechanistic foundation for the development of many stereospecific cross-coupling reactions.
© 2026. The Author(s), under exclusive licence to Springer Nature Limited.