Catalytic asymmetric synthesis of chiral spirocyclic diphenol derivatives

Abstract

The invention belongs to the field of organic synthesis, and discloses a catalytic asymmetric synthesis method of chiral spirocyclic diphenol derivatives: using chiral phosphoric acid as a catalyst, reacting a compound of formula I and / or compound of formula II to obtain a product: Among them, R 1 , R 2 , R 4 , R 5 , R 6 , R 7 each independently selected from any group, R 3 For the alkyl. This is a convenient, quick and direct method for constructing chiral spirocyclic diphenol structures. The synthesis method has the advantages of high yield, good enantioselectivity, tolerance to various functional groups and the like. In large-scale synthesis, the amount of the catalyst can be reduced to 0.1 mol%, which has application value in industrial production.

Description

technical field [0001] The invention belongs to the field of organic synthesis, in particular to a catalytic asymmetric synthesis method of chiral spirocyclic diphenol derivatives. Background technique [0002] Axichiral compounds have a wide range of applications in bioactive compounds, materials, organocatalysts, and ligands. Therefore, the asymmetric construction of axial chiral compounds has always been a research hotspot, and great progress has been made. Among the well-known structures in the art, axial chiral BINOL, BINAP and other biaryl derivatives have been widely used as chiral ligands / catalysts. Due to the importance of these structures, the catalytic asymmetric configuration of biaryl derivatives has been intensively studied, which can be achieved through stereoselective oxidation / crosslinking of two aryl substrates, asymmetrically controlled formation of The selective functionalization of aromatic compounds and other ways to obtain. [0003] Axial chiral 1,1...

AI Technical Summary

Problems solved by technology

[0003] Axial chiral 1,1'-spirodihydroindane-7,7'-diol (SPINOL for short) is a 1,1'-spirobiindane-containing compound widely used in asymmetric synthesis in recent years. The most basic and important structures of the chiral ligands (such as FuP, SDP, SpiroPAP, SPIDAM, SIPHOX, SpiroBOX, SCp, SITCP and CPA) of the backbone, but the asymmetric synthesis of SPINOL still lacks an effective way

At present, only a few studies have been involved in this field. Birman et al. first synthesized it by using a classical resolution strategy; in 2002, Zhou Qilin et al. developed a more practical method by using cinchodine chloride as a resolution reagent; recently , Zhao Yu et al. realized the kinetic resolution of SPINOL by enantioselective acylation catalyzed by N-heterocyclic carbene, however, this method only used one substrate, the ee value was lower than 50%, and the selection factor was 3.4

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