Method for synthesizing chiraltetrahydro naphthalenederivate through asymmetric hydrogenation on isoquinoline by means of iridium catalyst

Abstract

The invention discloses a method for synthesizing a chiraltetrahydro naphthalenederivate through asymmetric hydrogenation on isoquinoline by means of an iridium catalyst. A catalysis system applied in the method is a chiral bi-phosphine complex of metal iridium. The reaction is carried out under the conditions that the temperature is 25-60 DEG C; the volume ratio of tetrahydrofuran to dichloromethane in a solvent, namely a mixed solvent of tetrahydrofuran and dichloromethane is 1:1; the pressure is 13-50 Mpa; the ratio of a substrate to a catalyst is 50:1; the catalyst is a coordination compound of a (1,5-cyclooctadiene) iridium chloridedipolymer and a chiral bi-phosphine ligand. The corresponding chiral 1-position or 3-position substituted tetrahydro naphthalenederivate through hydrogenation on isoquinoline, and the enantiomeric excess of the derivate can reach 96%. The method is simple and practical in operation, raw materials are easy to obtain, the enantioselectivity is high, the yield is high, the reaction has atom economy, and the environment is friendly.

Description

Technical field [0001] The invention relates to a method for synthesizing chiral tetrahydroisoquinoline derivatives by using a homogeneous system of iridium to highly enantioselectively catalyze the hydrogenation of isoquinolines. technical background [0002] Tetrahydroisoquinoline and its derivatives are a class of alkaloids with a wide range of physiological and pharmacological activities, and have high research value and application prospects. Such compounds have a variety of potential drug activities, such as: anti-cancer, diuretic, sedative, anesthetic and anti-epileptic properties. Over the years, the research on the structure and biological activity of these compounds has attracted great attention from the pharmaceutical circles and synthetic organic chemists. The three common drugs of formula 1 all contain the tetrahydroisoquinoline structural unit: [0003] [0004] In addition to attracting people's attention as drugs, tetrahydroisoquinoline and its derivatives have al...

AI Technical Summary

Problems solved by technology

But so far, there are only a few examples of the successful use of asymmetric hydrogenation methods to synthesize chiral tetrahydroisoquinolines and their derivatives

The main reason is that isoquinoline is stable in nature, low in hydrogenation reaction activity, and has strong coordination ability, which can easily lead to catalyst poisoning

In 2006, Zhou’s group successfully achieved the asymmetric hydrogenation of 1-substituted isoquinolines for the first time using the strategy of chloroformate-activated substrates, but only achieved moderate yields and enantioselectivities (Reference 1: Lu, S.-M.; Wang, Y.-Q.; Han, X.-W.; Zhou, Y.-G. Angew. Chem., Int. Ed. 2006, 45, 2260)

[0006] It can be seen from the above examples that although some results have been obtained in the asymmetric hydrogenation of isoquinolines, there are also obvious limitations. For example, the scope of substrate application is not wide, the enantioselectivity is not high, and 3-substituted The asymmetric hydrogenation of isoquinoline has not been reported so far

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