Chiral diphosphine ligand, rhodium complex of chiral diphosphine ligand, preparation method and application of chiral diphosphine ligand and rhodium complex

Abstract

The invention relates to a chiral diphosphine ligand, a rhodium complex of the chiral diphosphine ligand, a preparation method and application of the chiral diphosphine ligand. Specifically, optically pure 1-phenylethylamine is subjected to lithiation, substitution and other reactions, and two aryl phosphine substituents are respectively introduced into ortho-positions of amino and phenyl of the optically pure 1-phenylethylamine to prepare the chiral diphosphine ligand; the chiral diphosphine ligand and rhodium salt are complexed to generate a corresponding rhodium complex. The rhodium complex of the chiral diphosphine ligand developed by the invention can catalyze the asymmetric hydrogenation reaction of beta-dehydroamino acid ester, shows excellent catalytic activity and very high enantioselectivity, provides a synthetic method suitable for industrialization for optically active beta-amino acid and derivatives thereof, and has a good application prospect.

Description

technical field [0001] The invention relates to a chiral bisphosphine ligand and its rhodium complex, a preparation method of the chiral bisphosphine ligand and its rhodium complex, and an asymmetric catalytic hydrogenation reaction of the rhodium complex in β-dehydroamino acid esters application as a catalyst. Background technique [0002] Chiral β-amino acids and their derivatives are an important class of molecules, and their fragments exist in many drug molecules (such as the anti-HIV drug dolutegravir, the hypoglycemic drug emiremide) [(1) Juaristi, E .; Quintana, D.; Escalante, J. Aldrichimica Acta 1994, 27, 3. (2) Nicolaou, K.C.; Dai, W.M.; 3) Hughes, D.L. Org. Process Res. Dev. 2019, 23, 716]. Therefore, the efficient asymmetric synthesis of chiral β-amino acids and their derivatives has received widespread attention [Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996, 25, 117]. [0003] The asymmetric catalytic hydrogenation of β-dehydroamino acid esters has the adv...

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Problems solved by technology

[0004] In the past forty years, great progress has been made in the research on the asymmetric catalytic hydrogenation of β-dehydroamino acid esters. A variety of metal complex catalysts modified with monophosphine ligands or bisphosphine ligands have been developed for this reaction, and some have achieved High enantioselectivity has been achieved, but the reported catalyst efficiency is usually not high (catalyst dosage is usually 1mol%), and there are also problems such as complex ligand structure, difficult synthesis, poor stability, and use of solvents that are not suitable for industrial production. Limit its industrial application [(1)Tang,W.; Zhang,X.Chem.Rev.2003,103,3029.(2)Xie,J.-H.Zhu,S.-F.;Zhou,Q. -L.Chem.Rev.2011,111,1713.Ager,D.J.; de Vries.A.H.M.;de Vries.J.G.Chem.Soc.Rev.2012,41,3340]

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