摘要：Chemical Development, AstraZeneca, SilkRoad Business Park, SK10 2NA Macclesfield, UK;

转自：康龙化成

Hydrogenation of Functionalised Pyridines witha Rhodium Oxide Catalyst under Mild Conditions

Sydney Williams, Leiming Qi, Robert J. Cox, Prashant Kumara and Jianliang Xiao*

Department of Chemistry, University ofLiverpool, Crown Street, L69 7ZD Liverpool,UK;

Chemical Development, AstraZeneca, SilkRoad Business Park, SK10 2NA Macclesfield, UK;

—Org. Biomol.Chem., 2024,1010

Recommended by Qilin Li_PDM

KEY WORDS: Hydrogenation(反应类型), Pyridines (原料), H2(原料),piperidine(产物), Rh2O3(催化剂)

ABSTRACT: Piperidinesare one of the most widely used building blocks in the synthesis ofpharmaceutical and agrochemical compounds. The hydrogenation of pyridines is aconvenient method to synthesise suchcompounds as it only requires reactant, catalyst, and a hydrogen source.However, this reaction stillremainsdifficult for the reduction of functionalised andmulti-substituted pyridines. Here we report the use of a stable, commerciallyavailable rhodium compound, Rh2O3, forthe reduction of various unprotected pyridines. The reaction only requires mildconditions, and the substrate scope is broad, making it practically useful.

Recentwork on the hydrogenation of pyridines

Hydrogenationof alkyl pyridine

Hydrogenation of alcohol pyridines andamine-functionalised pyridines

Hydrogenation of phenyl pyridines

Hydrogenation of pyridines with an EDG orEWG at the 4-position

In conclusion,Prof. Xiao and coworkers have identified the commercially available rhodiumoxide to bea highly active catalyst for the hydrogenation of a wide variety of unprotectedpyridines under mild conditions. The optimal conditions tolerate anumber offunctional groups, including alcohols, amines and carbonyls. The reaction canalso reduce multi substituted pyridines to give the corresponding cispiperidines as the major product. Issues can arise with chemoselectivity whenthe functional group attached to the pyridine ring can also be reduced, forexample olefins, nitro groups and ketones, which were also reduced during thereaction. It is suspected that the hydrogenation proceeds via initial hydridetransfer to the 4th position of pyridine ring, as electrondonating and/or sterically bulky groups hinder the reaction. Study is ongoingin the lab to explore further the potential of this easily available,easy-to-handle catalyst.

来源：新浪财经