A method for preparing chiral allylamine compounds with high chemical and stereoselectivity

Abstract

The invention discloses a method for preparing chiral allylamine compounds with high chemical and stereoselectivity. In metal reagent Ni(COD) 2 , under the action of chiral bisphosphine ligands and acid additives, 1,3-conjugated dienes and amines are dissolved in organic solvents and reacted, separated and purified by column chromatography to obtain chiral allylamine compounds. The method of the invention can efficiently synthesize chiral allylamine compounds, has mild reaction conditions, wide substrate range, and excellent regioselectivity, chemoselectivity and stereoselectivity. For amine substrates with two nucleophilic sites, the reaction site can be well identified, and the ee value is as high as 99%. Furthermore, the reaction can be scaled up on a gram-scale, and the catalyst loading can be reduced below 1%. It can also react efficiently to drug molecules such as desloratadine, which provides a new method for the derivatization of drug molecules and the synthesis of complex drug molecules.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method and application for preparing chiral allylamine compounds with high chemical and stereoselectivity. Background technique [0002] Chiral amine fragments widely exist in natural products and bioactive molecules [a) Lough, W.J.; Wainer, I.W. Chirality in Natural and Applied Science, Blackwell: Oxford, UK, 2002; b) Francotte E.; Lindner, W. Chirality in Drug Research, Wiley-VCH: Weinheim, 2006; c) Nugent, T.C. Chiral Amine Synthesis: Methods, Developments and Applications, Wiley-VCH: Weinheim, 2010]. Based on its important application value, the synthesis of chiral amines has attracted great interest and widespread attention in the field of organic chemistry [a) Li, W.; Zhang, X. Stereoselective Formation of Amines, 2014; b) Nugent, T.C.; El-Shazly, M. Adv. Synth. Catal. 2010, 352, 753-819; c) Patil, M. D.; Grogan, G.; Bommarius, A.; Yun, H. ACS Catal. 2018, 8,...

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Problems solved by technology

[0003] Transition metal-catalyzed asymmetric hydroamination of allenes, alkynes and conjugated alkenes has been reported [a) Lutete, L.M.; Kadota, I.; Yamamoto, Y.J.Am.Chem.Soc.2004,126,1622- 1623; b) Cooke, M.L.; Xu, K.; Breit, B. Angew. Chem. Int. Ed. 2012, 51, 10876-10879; c) Xu, K.; Wang, Y.H.; , B.Chem.Sci.2016,7,3313-3316; d) Athira, C.; Changotra, A.; Sunoj, R.B.J.Org.Chem.2018,83, 2627-2639; , Y.W.; Zhang, G.Z.Tetrahedron Lett.2018, 59, 347-355; f) Park, S.; Malcolmson, S. J.ACSCatal.2018, 8, 8468-8476; g) Berthold, D.; Geissler, A.G.A.; Giofre, S. ; Breit, B.Angew.Chem.Int.Ed.2019,58,9994-9997], but most of them are limited to noble metal catalysts such as Rh and Pd, and the scope of substrates is relatively narrow, and the tolerance of functional groups is poor

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