Method for synthesis of 3-piperidone derivatives through iridium catalytic hydrogenation

Abstract

A method for synthesis of 3-piperidone derivatives through iridium catalytic hydrogenation is provided, wherein a used catalyst is a triphenylphosphine complex of iridium. A reaction can be carried out under the following conditions: the temperature is 40-60 DEG C; the solvent is 1,2-dichloroethane; the pressure is 20-50 atmospheric pressures; the ratio of a substrate to a catalyst is 100 to 1; and the catalyst is a complex of chloro(1,5-cyclooctadiene)iridium(I) dimer and triphenylphosphine. Hydrogenation of 3-hydroxypyridine benzyl bromide salt can obtain the 3-piperidone derivatives with excellent chemoselectivity, the highest yield can reach 97%, and the chemical selectivity of ketones and alcohols is greater than 20:1. The method has the advantages of simple and convenient operation, easily obtained raw materials, high chemoselectivity, and good yield, and provides an atom economic and environment-friendly route for synthesis of a series of 3-piperidone derivatives.

Description

technical field [0001] The invention relates to a method for synthesizing 3-piperidone derivatives through iridium-catalyzed hydrogenation of 3-hydroxypyridinium salt with high chemoselectivity and high yield. technical background [0002] 3-piperidone is a very important intermediate in the synthesis of 3-hydroxyl and 3-aminopiperidine, and 2-substituted 3-hydroxyl or 3-aminopiperidine structures are widely found in natural products and pharmaceutically active molecules. Natural products such as Febrifugine and Isofebrifugine, the former having potent antimalarial activity [(a) Koepfli, J.B.; Mead, J.F.; Brockman, Jr., J.A., J. Am. Chem. Soc. 1949, 71, 1048.]. Pharmaceutically active molecules such as (+)-L-733,060 and (+)-CP-99,994 exhibit regulatory effects on multiple physiological processes, such as neurogenic inflammation, pain transmission, immune response regulation, etc. [(a) Baker, R .; Harrison, T.; Hollingworth, G.J.; Swain, C.J.; Williams, B.J. EP528, 495A1, 1...

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Problems solved by technology

[0004] Most existing synthetic methods have long routes, cumbersome steps, and are difficult to enlarge and synthesize [(a) Calvez, O.; Langlois, N. Tetrahedron Lett.1999, 407099; (b) Tsai, M.-R.; Chen, B.-F.; Cheng, C.-C.; Chang, N.-C.J.Org.Chem.2005,70,1780; (c) Pansare, S.V.; Paul, E.K.Org.Biomol.Chem., 2012 ,10,2119.]

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