Synthesis method of chiral 4, 6-dioxooctahydropyrrolo[3, 4-c]pyrrole-1-carboxylate compound

Abstract

The invention provides a synthesis method of chiral 4, 6-dioxooctahydropyrrolo[3, 4-c]pyrrole-1-carboxylate. According to the method, an N-(phenyl methylene)glycine ester compound and a 3-substituted maleimide compound are taken as raw materials, and the chiral 4, 6-dioxooctahydropyrrolo[3, 4-c]pyrrole-1-carboxylate compound is prepared with high yield, high regioselectivity, high diastereoselectivity and high enantioselectivity under the catalysis of a chiral copper catalyst. The chiral copper catalyst is prepared from copper salt catalyst precursors such as [Cu(CH3CN)4]ClO4 and chiral ferrocene P, S-ligand in situ. The catalytic reaction needs to be carried out at -40 DEG C to room temperature by taking methylbenzene, benzene and the like as solvents under the action of alkali additives such as triethylamine. The catalytic reaction has the characteristics of mild conditions, simplicity and convenience in operation, cheap and easily available substrates, excellent regioselectivity and stereoselectivity, high yield and the like.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a synthesis method of chiral 4,6-dioxoctahydropyrrolo[3,4-c]pyrrole-1-carboxylate compounds. Background technique [0002] Chiral pyrroline structures are widely found in drugs, pesticides, spices, and natural products. Therefore, the efficient and high stereoselective construction of chiral pyrroline structures with diverse structures has always been a frontier and challenge in the research of organic synthetic chemistry and asymmetric catalysis. topic. Catalytic asymmetric dipolar cycloaddition between methylimine ylides and unsaturated alkenes is one of the most direct and efficient methods to construct chiral pyrroline structures. In the past two decades, this catalytic asymmetric cycloaddition method has made important progress: 1) the discovery of many highly efficient chiral metal and organocatalyst systems; 2) the imine ylide 1,3-dipole 3) It has been widely...

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Problems solved by technology

But it is very surprising that its 3-substituted derivatives are difficult to undergo [3+2] cycloaddition reaction with the 1,3-dipole of amethyridine ylide due to the influence of steric hindrance

Sansano et al. found that [3+2] dipolar cycloaddition reaction of N-ethyl-3-methylmaleimide and methylimide ylide under the catalysis of Ag / (S)-BINAP catalyst, but the reaction Regioselectivity is extremely low (44 / 56), and this is the only reported example of catalytic asymmetric 1,3-dipolar cycloaddition involving 3-substituted maleimides (C.Najera, M.de Gracia Retamosa, J.M. Sansano, A. de Cozar, F.P. Cossio, Tetrahedron: Asymmetry, 2008, 19, 2913)

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