Preparation method and application of chiral spirocyclic aminophosphine ligand substituted at 3-position on pyridine ring

Abstract

The invention relates to a preparation method and application of a chiral spirocyclic aminophosphine ligand substituted at the 3-position on a pyridine ring. The chiral spirocyclic aminophosphine ligand substituted at the 3-position on the pyridine ring is a compound shown in Formula 1, or its racemate or optical isomer, or a catalytically acceptable salt thereof, and the main structural feature is that it has Chiral spiroindane skeleton and with pyridine group. The 3-position substituted chiral spirocyclic aminophosphine ligand on the pyridine ring can be composed of 7-diaryl / alkylphosphino-7′-amino-1,1′-spirodihydroindenes with a spiro ring skeleton Synthesized as a chiral starting material. After the chiral spirocyclic aminophosphine ligand substituted at the 3-position on the pyridine ring forms a complex with a transition metal (iridium) salt, it can be used to catalyze the asymmetric catalytic hydrogenation reaction of α-arylamine-substituted lactone compounds. It exhibits high catalytic activity (TON up to 19000) and enantioselectivity (up to 99% ee), and has practical value.

Description

technical field [0001] The invention relates to a preparation method and application of a 3-position substituted chiral spirocyclic aminophosphine ligand on a pyridine ring, in particular to a preparation method of a chiral spirocyclic aminopyridine tridentate ligand with a spiro ring skeleton and the application thereof. The application thereof in the asymmetric catalytic hydrogenation reaction of β-aryl alkylene malonates belongs to the technical field of organic synthesis. Background technique [0002] Asymmetric catalytic hydrogenation is the greenest, atom-economical and effective method for synthesizing chiral compounds, and has been practically applied in the industrial production of chiral drugs, pesticides, and fragrances. The efficiency and selectivity of asymmetric catalytic hydrogenation reactions depend on the activity, stability, and efficiency of chiral catalysts. Therefore, the development of novel and efficient chiral ligands and their catalysts is the key ...

AI Technical Summary

Problems solved by technology

However, there is still no direct synthesis of malonate chiral compounds containing arylalkyl-substituted tertiary carbon chiral centers at the β-position through the asymmetric catalytic hydrogenation of β-arylalkylene malonates. literature report

In addition, although there are reports in the literature that asymmetric catalytic hydrogenation of α,β-unsaturated carboxylic acids and ester derivatives is used to synthesize their deesterified products (Hou, G.; etal.J.Org.Chem.2016,81 , 2070; Kitamura, M.; et al. Tetrahedron 2007, 63, 11399; Diéguez, M.; et al. Adv. Synth. Catal. 2017, 359, 2801; Zhou, J.; et al. Org. Lett. 2006,18,5344), but the scope of the substrate is narrow, the catalyst consumption is high (2 ), and can only give high enantioselectivity to a single-configuration substrate (Z or E)

These factors limit the application of asymmetric catalytic hydrogenation of α,β-unsaturated carboxylic acids and ester derivatives, which is a high atom-economical reaction method.

Images