Copper/iridium synergistically catalyzed asymmetric allylation/2-aza-cope rearrangement and its application

Abstract

The invention discloses a novel copper / iridium synergistically catalyzed allylation / 2-aza-Cope rearrangement reaction involving the participation of methyleneamine ylides to synthesize chiral multi-substituted homoallylamine derivatives. The method is as follows: in an organic solvent, under the protection of an inert gas, using allyl carbonate and amino acid-derived imine as raw materials, using copper complex and iridium complex as co-catalysts, adding cesium carbonate, at 25 ° C React at high temperature for 12-24 hours, add a high boiling point solvent at 25-100°C and continue to react for 4-24 hours, after hydrolysis, protection and other post-treatments, the target compound is obtained by column chromatography.

Description

technical field [0001] The invention belongs to the field of chemical medicine, and in particular relates to a copper / iridium synergistic catalyzed asymmetric allylation / 2-aza-Cope rearrangement reaction to synthesize terminally substituted homoallylamine derivatives and a preparation method and application thereof. Background technique [0002] Chiral amine building blocks are widely found in compounds with important biological activities (such as marketed drugs) and transition metal ligands. Therefore, efficient, universal, and easy-to-use chiral amine synthesis methods have always been a hot research field in synthetic chemistry. Methyleneamine ylide, as a common synthetic intermediate, is cheap and easy to obtain, and is widely used in the synthesis of nitrogen-containing heterocycles and unnatural amino acid derivatives. However, so far, no research group has reported the use of asymmetric catalysis to synthesize chiral amines using methyleneamine ylides ((a) Nugent, T...

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Problems solved by technology

However, so far, no research group has reported the use of asymmetric catalysis to synthesize chiral amines using methyleneamine ylides ((a) Nugent, T.C. Chiral Amine Synthesis: Methods, Developments and Applications, Wiley-VCH, 2010. (b) Puentes , C.O.Kouznetsov, V.J.Heterocycl.Chem.2002,39,595; (c) Przheval'skii, N.M.Grandberg, I.I.Usp.Khim.1987,56,814; (d) Kobayashi, S.; Mori, Y.; Fossey, J.S; Salter , M.M.Chem.Rev.2011,111,2626; (e) Yus, M.; González-Gómez, J.C.; Foubelo, F.Chem.Rev.2011,111, 7774; (f) Yus, M.; Gómez, J.C.; Foubelo, F. Chem. Rev. 2013, 113, 5595.)

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