Method for preparing chiral spiro [2.4] heptane compound through palladium-catalyzed asymmetric cycloaddition reaction

Abstract

The invention provides a method for preparing chiral spiro [2.4] heptane compounds through palladium-catalyzed asymmetric cycloaddition reaction, which comprises the following steps: in a solvent, under the synergistic catalysis of a palladium catalysis system and an organic urea tertiary amine catalyst, gamma-methylene-delta-valerolactone compounds I and indole nitroolefin compounds II are subjected to cycloaddition reaction, and the chiral spiro [2.4] heptane compounds are obtained. A chiral spiro [2.4] heptane compound III is obtained; the palladium catalysis system is composed of a palladium catalyst and a chiral ligand, and the chiral ligand has a structure as shown in a formula IV; the organic urea tertiary amine catalyst has a structure as shown in a formula V. The spiro compound is constructed through the palladium-catalyzed asymmetric cycloaddition reaction, and the method has the advantages of low catalyst cost, convenience in operation, wide substrate application range, cheap and easily available reaction raw materials and the like.

Description

technical field [0001] The invention relates to a method for preparing chiral spiro[2.4]heptane compounds through palladium-catalyzed asymmetric cycloaddition reaction, belonging to the technical field of organic synthesis. Background technique [0002] Transition metal-catalyzed intermolecular cycloaddition reactions are one of the most efficient methods for the synthesis of cyclic scaffolds. Since Trost and Chan first reported 2-acetoxymethyl-3-allyltrimethylsilane to generate 1,3-dipolar intermediates in 1979 (Trost, B, M.; Chan, D, M, T.J. Am.Chem.Soc.,1979,101,6429-6432.), the transition metal-catalyzed dipolar cycloaddition reaction between active zwitterionic intermediates and unsaturated acceptors has been widely used to construct multifunctional rings compound. In 2007, Shintani and Hayashi reported for the first time that the precursors γ-methylene-δ-valerolactones (GMDVs) could generate 1,4-dipoles by decarboxylation under the action of zero-valent palladium (Sh...

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Problems solved by technology

[0003] In contrast, asymmetric [3+2] cycloaddition reactions via anion attack on the central carbon of π-allylpalladium intermediates to form multisubstituted chiral spirocycles have been rarely reported

In 2012, Shintani and Hayashi reported the palladium-catalyzed asymmetric [3+2] / [4+2] cycloaddition of GMDVs with isocyanates to give 2-pyrrolidones (Shintani, R.; Ito, T.; Hayashi, T. Org. Lett., 2012, 14, 2410-2413; Shintani, R.; Ito, T; Nagamoto, M.; Otomo, H.; .), but substrates are limited to isocyanates and functional groups are less tolerant

In 2020, the Trost research group reported two unique asymmetric cycloaddition pathways involving aliphatic 1,4-dipoles, and successfully synthesized chiral spiro[2.4]heptane compounds (Trost,B,M .; Jiao, Z.; Liu, Y.; Min, C.; Hung, C,-I.J.Am.Chem.Soc.,2020,142,18628-18636.), however, only 4 successful Synthetic product case, low application value

[0004] From the above, it can be seen that the application range of the existing synthetic methods is relatively small. Therefore, exploring the new reaction mode of 1,4-dipole to prepare chiral spiro[2.4]heptane compounds is very important for the development of palladium-catalyzed asymmetric rings. Propanation is very necessary

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