1, 1'-ferrocene perfluoroalkyl phosphine nitrogen ligand as well as preparation method and application thereof

Abstract

The invention relates to a 1, 1'-ferrocene perfluoroalkyl phosphine nitrogen ligand as well as a preparation method and an application thereof. The preparation method of the 1, 1'-ferrocene perfluoroalkyl phosphine nitrogen ligand comprises the following steps: (1) reacting oxazoline bromoferrocene with a butyl lithium compound in an organic solvent under the condition of existence of an additive; (2) mixing reaction liquid obtained in the step (1) with triphenyl phosphite; and (3) in the solvent, reacting an isodecyl diphenyl phosphite derivative obtained in the step (2) and cesium fluoride with TMSCnF2n+1. The invention also relates to the application of the ligand in an asymmetric allyl displacement reaction catalyzed by metallic palladium. The ligand provided by the invention can be used for catalyzing the allyl displacement reaction of single substituted allyl carbonic ester in a high domain selectivity and high enantioselectivity manner. The synthetic method is simple, mild in conditions, high in yield, convenient in purification and suitable for industrial production; starting materials are low in cost and easy to obtain.

Description

technical field [0001] The invention relates to a 1,1'-ferrocene perfluoroalkylphosphine nitrogen ligand, its preparation method and application. Background technique [0002] Transition metal-catalyzed asymmetric allyl substitution reactions are one of the important reactions for the formation of carbon-carbon bonds and carbon-heteroatom bonds, and are widely used in total synthesis. Metals such as palladium (Pd), rhodium (Rh), ruthenium (Ru), iridium (Ir), molybdenum (Mo), tungsten (W), nickel (Ni) and copper (Cu) can all catalyze this reaction. The most, and the most detailed study is the metal palladium. Chemists represented by Trost have done a lot of research work on this reaction, which has greatly developed and applied this reaction. Nevertheless, there are still some challenges in the application of allylation reactions and have not been well resolved. One of the difficulties is regioselectivity. In palladium-catalyzed allyl substitution reactions, for monosubsti...

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Problems solved by technology

Moderate to excellent regioselectivity and enantioselectivity can be obtained for linear and branched allyl substrates, especially when the allyl substrate is 1-naphthyl, high regioselectivity and enantioselectivity, but unsatisfactory results for aryl substituents in general, especially those containing electron-withdrawing groups, and poor results for alkyl-substituted allylic substrates, with almost no Regional selectivity [(a) R.;Pfaltz,A.Angew.Chem.,Int.Ed.1998,37,323.(b)Hilgraf,R.;Pfaltz,A.Synlett.1999,1814.(c)Hilgraf,R.;Pfaltz,A. Adv. Synth. Catal. 2005, 347, 61.]

In 2001, Hou Xuelong and Dai Lixin's group designed and synthesized 1,1'-ferrocene phosphine nitrogen ligand SIOC-PHOX. In the reaction of malonate and benzylamine with a monosubstituted allyl substrate, it can / 20~99 / 1 regioselectivity, 87~97% enantioselectivity to obtain branched chain product-based products. Alkylation and amination [You,S.-L.;Zhu,X.-Z.;Luo,Y.-M.;Hou,X.-L.;Dai,L.-X.J.Am.Chem. Soc.2001,123,7471.], but the catalyst needs to synthesize two chiral centers, and the synthesis method is relatively complicated

Recently, Shen Qilong's group reported a perfluoroalkyl-substituted 1,2-ferrocene phosphine nitrogen ligand, which achieved better regioselectivity and enantioselectivity in palladium-catalyzed asymmetric allylation reactions[ Hu,Z.;Li,Y.;Liu,K.;Shen,Q.J.Org.Chem.2012,77,7957.], but the ligand synthesis yield is low, not suitable for industrial production

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