Related Experiment Video
Updated: Sep 10, 2026

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
Direct Access to Chiral Piperidines by Enantioselective HAT-Initiated C(sp3)─H Oxidation
Sethuraman Muthuramalingam1, Josep M Luis1, Arnau Call1
1Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química, Universitat de Girona, Girona, Catalonia, Spain.
Abstract:
Enantioselective C(sp3)─H functionalization reactions are appealing synthetic organic chemistry tools to streamline access to valuable chiral molecules from simple precursors. Chiral piperidines are ubiquitous motifs in pharmaceuticals and natural products, yet methods for their preparation from simple non-chiral precursors remain limited. We report a catalytic strategy for the preparation of chiral piperidines by α-C(sp3)─H oxidation of achiral piperidines using hydrogen peroxide as oxidant and an evolved manganese catalyst in 2,2,2-trifluoroethanol. Piperidines are desymmetrized to afford chemically versatile chiral N,O-acetal products in good yields, with high enantio- and diastereoselectivity. The resulting products serve as key intermediates to access a diverse range of functionalized piperidines while retaining chirality. Mechanistic studies indicate that the reaction proceeds via a highly enantioselective hydrogen atom transfer (HAT) followed by an electron transfer to generate a chiral iminium cation that is rapidly hydroxylated. Statistical models correlating reaction performance to molecular features provide a mechanistic basis for the stereoselective dictating elements and offer a tool for future reaction development.
Related Concept Videos
Sharpless Epoxidation
Prochirality
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Chirality at Nitrogen, Phosphorus, and Sulfur
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Radical Anti-Markovnikov Addition to Alkenes: Overview
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
