Asymmetric Anti-Hydrogenation of Tetrasubstituted Alkenes
Year: 2026
Type: preprint
Abstract: Asymmetric alkene hydrogenation is a foundational method for constructing chiral molecules, with broad applications in pharmaceutical synthesis, natural-product synthesis and materials science. However, the stereochemical outcomes accessible through conventional asymmetric hydrogenation are constrained by its underlying mechanism. Established catalysts, including complexes of iridium, rhodium, ruthenium and platinum, typically deliver both hydrogen atoms to the same face of an alkene to give syn-hydrogenation products. The complementary process, in which hydrogen atoms are stereoselectively delivered from opposite alkene faces, would provide direct access to complementary stereochemical products, but remains poorly developed. Here we show that engineered heme proteins catalyze asymmetric anti-hydrogenation of unactivated cyclic tetrasubstituted alkenes. These genetically encoded catalysts operate through a cooperative radical mechanism in which an active-site iron hydride delivers a hydrogen atom to one face of the alkene to generate a transient carbon-centered radical, which is subsequently quenched from the opposite face by a distal cysteine residue. The spatially separated hydrogen-atom donors thereby enable sequential stereodetermining events, furnishing anti-hydrogenated products with high diastereo-
Source: ChemRxiv
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7214669335