Preparation method of alpha-substituted-beta-hydroxynitrile compound and derivative thereof

Abstract

The invention provides a preparation method of an alpha-substituted-beta-hydroxynitrile compound and a derivative thereof. A compound with a structure as shown in a formula (I) is reacted under the action of a specific metal catalyst to obtain a compound with a structure as shown in a formula (II), and a result shows that the reaction adopts an asymmetric transfer hydrogenation reaction. The method not only has the advantages of mild reaction conditions, high yield, excellent diastereoselectivity and enantioselectivity of the product and the like, but also has the advantages of low catalyst consumption in the reaction system and high catalytic efficiency.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a preparation method of α-substituted-β-hydroxynitrile compounds and derivatives thereof. Background technique [0002] Chiral β-hydroxynitrile compounds are an important class of organic synthons because the cyano functional group can be converted into valuable functional group compounds such as amino, carboxyl and amide efficiently and conveniently; moreover, optically active α-substituted -Derivatives of β-hydroxynitrile compounds, such as 1,2-aminoalcohol, 1,3-aminoalcohol, etc. are a very important and basic chiral skeleton, which are common in various natural products and various biological activities Molecules, chiral auxiliary agents and chiral ligands, therefore, the synthesis of α-substituted-β-hydroxynitrile compounds is of great significance. [0003] In the prior art, there are many synthetic methods for α-substituted-β-hydroxy nitrile compounds, for examp...

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Problems solved by technology

[0003] In the prior art, there are many synthetic methods for α-substituted-β-hydroxy nitrile compounds, for example, the trans-selective condensation between lithium nitrile reagent and aldehyde provides a method for constructing ortho-substituted-hydroxycarbonylcarbonyl Direct strategy, however, the stereochemical results of aldol condensation are difficult to control (Chem.Commun.2008, 2212-2214); direct reduction of α-substituted-β-carbonyl nitrile compounds is also the construction of α-substituted-β-hydroxy One of the most direct synthetic methods of nitrile compounds, such as: in 2001, Dalpozzo et al. reported a TiCl 4 / BH 3 or LiBH 4 / CeCl 3 Efficient diastereoselective reduction of α-substituted-β-carbonyl nitriles, but the reaction requires low temperature to obtain high diastereoselectivity and the reaction requires an excess of Lewis acid and reducing agent, the yield of the reaction are not high (Eur.J.Org.Chem.2001,2001.); in 2016, Romano and colleagues reported an enzymatic reduction of α-substituted-β-carbonyl nitriles, although the diastereoselectivity of the reaction and enantioselectivity are relatively excellent, but the transformation can be applied to very few substrates (Tetrahedron 2016,72,3974-3979.); In addition, Rimoldi et al. reported the only case of transition metal-catalyzed asymmetric transfer hydrogenation method to reduce α-substituted-β-carbonyl nitriles, however, the enantioselectivity and diastereoselectivity results of the method reported in this paper are not ideal (Tetrahedron:Asymmetry 2014,25,1031- 1037.)

It can be seen that in the synthesis of α-substituted-β-hydroxynitrile compounds, there is currently no efficient and highly stereoselective synthetic method

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