Method for preparing piperidine compound by reducing pyridine compound through hydrogen transfer

Abstract

The invention discloses a method for preparing a piperazine compound through a hydrogen transfer reduction of a pyridine compound, belonging to the field of organic synthesis. Under mild conditions, pyridine derivatives are used as raw materials, oxazolidine is used as a hydrogen transfer reagent, and cheap transition metals such as copper, cobalt, silver, palladium and the like are used as catalysts for catalysis of a hydrogen transfer reaction on 1,2,3,4-substitution sites, so a series of hydrogen transfer reduction product piperidine compounds are prepared, wherein the oxazaborolidine is obtained by a reaction of amino acid with a tetrahydrofuran complex of borane. The method has the advantages that product yield is high, reaction conditions are mild, the general applicability of raw materials is good, a hydrogen transfer reagent is cheap and easy to obtain, and good reproducibility can still be shown after quantitative reaction is conudcted. Therefore, the method of the invention provides an effective scheme for the industrial production of other high-value compounds containing the structure in the future.

Description

Technical field:[0001]The present invention belongs to organic chemistry, including pharmaceutical intermediate preparation and related chemical technology, and more particularly to a method of preparing a hydrogen transfer reduction pyridine compound.Background technique:[0002]N-heterocyclic compounds and their hydrogenated reduction derivatives, particularly piperidine compounds, are important structural units that constitute a number of natural products, drugs, and other biologically active substances. There is a variety of physiological activities with piperidine for the parent, there is potential application value in anti-cancer, antibacterial, antiviral, and treatment of diabetes; there is also an application in the field of polymer materials. [Li Ming. catalytic high selective synthetic piperidin derivative [D]. Dalian University of Technology, 2019. Yang Zihui, Tian Wei, Zhang Li. Research Progress of Piperidine Compounds with Pesticine Activity [J]. World Pesticide , 2017,3...

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Problems solved by technology

In the past few years, some research groups have discovered metal-free borane-catalyzed pyridine reduction[Liu Y, Du H. Metal-free borane-catalyzed highlystereoselective hydrogenation of pyridines[J]. Journal of the American Chemical Society,2013, 135(35):12968-12971. Eisenberger P, Bestvater B P, Keske EC, et al. Hydrogenations at room temperature and atmospheric pressure with mesoionic carbene-stabilized borenium catalysts[J]. Angewandte Chemie-International Edition, 2015, 54(8) :2467-2471.Gandhamsetty N, Park S,ChangS.Selective silylative reduction of pyridines leading to structurally diverse acyclic compounds with the formation of sp3 c–si bonds[J].Journal of the American Chemical Society.137(48):15176-15184 .] Despite these advances, there are still disadvantages: 1) For hydrogenation and transfer hydrogenation reactions, a large number of ortho substituents must be present on the pyridine ring to circumvent catalyst deactivation through nitrogen coordination; 2) unsaturated Functional groups such as alkenes, esters, ketones, nitriles and nitro groups are rarely compatible due to their ease of reduction

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