Synthesis method of chiral trans-2-substituted naphthenic alcohol

Abstract

The invention relates to a synthesis method of chiral trans-2-substituted naphthenic alcohol. The invention provides a method for synthesizing chiral trans-cycloalkanol through asymmetric hydrogenation of palladium-catalyzed 2-substituted cyclic ketone. According to the method,a chiral diphosphine P-P * complex of metal palladium is taken as a catalyst, an acid additive is used in cooperation, asymmetric hydrogenation is carried out on a 2-substituted cyclic ketone compound to obtain a corresponding chiral trans-cycloalkanol compound. the enantiomeric excess of the chiral trans-cycloalkanol compound can reach 97% at most, and the trans-selectivity of the chiral trans-cycloalkanol compound is up to 20: 1. The method is simple and convenient to operate, practical, easy to implement, high in yield, high in atom economy and environment-friendly; the catalyst is commercially available; the reaction conditions are mild; and the method has a potential practical application value.

Description

technical field [0001] The invention belongs to the field of asymmetric hydrogenation synthesis, and in particular relates to a method for synthesizing chiral trans-cycloalkanol by using palladium homogeneous system to highly enantioselectively catalyze the hydrogenation reaction of 2-substituted cyclic ketones. Background technique [0002] The importance of chiral cycloalkanols with consecutive stereocenters has been widely recognized in natural products, pharmaceuticals and other bioactive molecules (Eur.J.Org.Chem., 2009, 1477; Curr.Org.Chem., 2014 , 18, 641; Chem. Rev., 2016, 116, 5744.). Transition metal-catalyzed asymmetric hydrogenation of corresponding cyclic ketones is one of the most efficient and facile methods due to their high atom economy and environmental friendliness (Chem.Soc.Rev., 2013, 42, 497; Chem.Soc.Rev ., 2013, 42, 728; Chem. Rev., 2014, 114, 2130; Chem. Rev., 2016, 116, 14769; Chin. J. Chem., 2018, 36, 443.). At present, the asymmetric hydrogenati...

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Problems solved by technology

It can be seen from the literature that although the asymmetric hydrogenation of chain ketones to construct trans-alkyl alcohols has been successful (Angew.Chem.Int.Ed., 2004,43,882; Tetrahedron Lett.,2009,50,2676; .) However, for 2-substituted cyclic ketones, except for the functional group containing an ester-directing group at the 2-position, there are few examples of other 2-substituted cyclic ketones being synthesized by asymmetric hydrogenation into trans cycloalkanols (J .Am.Chem.Soc., 1989,111,9134; J.Am.Chem.Soc., 1995,117,4423; Org.Biomol.Chem., 2012,10,5253.), literature (Tetrahedron:Asymmetry, 1992,3,1029), though using 2-phenylcyclohexanone and 2-methylcyclohexanone as substrates, through the silane reduction system catalyzed by asymmetric rhodium, asymmetric reduction was carried out, and trans cycloalkanol was synthesized , but the diastereoselectivity of the product is low, and the anti-cis ratio in the cycloalkanol product is lower than 4:1

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