New method for efficiently chiral inductive preparing R-/S- diaryl methyl substituted chiral organic phosphonate

Abstract

The invention provides a method for efficiently and high-selectively compounding chiral R- / S- diaryl methyl substituted chiral organic phosphonate derivatives containing different substituting functional groups. Cesium carbonate is taken as a catalyst; chiral P(O)-H compound and 4-aryl methylene-2,6-di-tert-butyl-2,5-cyclohexadiene-1-ketone compounds are taken as reaction substrates; an organic solvent is added into a reaction system. The method has the advantages that the catalyst is low-cost and can be easily acquired; the substrates are high in applicability; the reaction conditions are mild, safe and reliable; the three-dimensional enantioselectivity of the acquired target product is above 99% and the yield is above 80%. The method can overcome the defects of low enantioselectivity, complex reaction steps, and the like, of the traditional reaction for compounding chiral R- / S- diaryl methyl substituted chiral organic phosphonate derivatives, can avoid the traditional chiral resolution method and has an excellent industrial application prospect. The invention also provides the corresponding chiral R- / S- diaryl methyl substituted chiral organic phosphonate derivatives containing different substituting functional groups.

Description

technical field [0001] The invention relates to the field of catalytic synthesis of chiral organic phosphonate compounds, in particular to a method of combining chiral P(O)-H compounds with 4-arylmethylene-2,6-di-tert-butyl -2,5-Cyclohexadien-1-one compound undergoes high stereoselective 1,6-addition reaction to prepare R- / S-diarylmethyl-substituted chiral organic phosphonate derivatives Preparation. Background technique [0002] R- / S-diarylmethyl substituted chiral organic phosphonates are an important class of organic intermediates. They are widely used in the preparation of chiral drugs, anticancer agents, high-efficiency flame retardants, and chiral catalyst ligands. Among the various organophosphorus compounds with different coordination, the research on one, two and six coordination compounds is the latest work, and their technology as organic synthesis building blocks is not yet mature. At present, organophosphorus reagents are mainly limited to three-, four-, and ...

AI Technical Summary

Problems solved by technology

However, currently the R - / S -The synthetic method of diarylmethyl substituted chiral organic phosphonate compound has not been reported yet, and above-mentioned method generally all adopts air-sensitive reagent (P(OR) 3 compounds, phosphorus oxychloride, etc.), special ligands (ferrocene ligands, carbene ligands, etc.) Defects such as utilization, harsh reaction conditions, cross-substrate applicability, low yield, and large environmental pollution

[0005] So far, including R - / S - The efficient synthesis of diarylmethyl substituted chiral organic phosphonate compounds has the disadvantages of raw material quality, production safety (compounds such as trialkyl phosphite and phosphorus oxychloride are highly corrosive), chiral resolution Difficulty in classification, product stability and purity, etc. The synthesis technology is relatively difficult. At present, only a few companies in the United States, Japan and other countries are producing, while the current situation of high-end chiral organic phosphonate products in my country mainly rely on imports