Molybdenum-Catalyzed Diastereoselective Anti-dihydroxylation Of Secondary Allylic Alcohols

Polyhydroxyl structural units are widely present in natural product structures and pharmaceutical molecules.In addition,the hydroxyl group is also an important synthetic building block in organic synthesis,and it can be further converted into other functional groups.Therefore,it is of great significance to develop highly efficient,green and practical methods for constructing polyhydroxy compounds.In recent decades,a series of methods for direct or indirect dihydroxylation of alkenes have been developed,and vicinal diols can be prepared from alkenes.On the basis of intensive literature research as well as our expertise of transition metal-catalyzed epoxidation and dihydroxylation of alkenes,we envisaged the molybdenum-catalyzed diastereoselective anti-dihydroxylation of secondary allylic alcohols by using hydrogen peroxide as an oxidant.We speculated that this reaction undergoes with two key steps:the initial epoxidation and the subsequent hydrolysis.The diastereoselectivity of the entire reaction depends on the diastereoselectivity of the first step to form an epoxide and the regioselectivity of the ring-opening reaction in the hydrolysis step.The main contents include the following two sections:Section I:The research progress for dihydroxylation of alkenes and diastereoselective synthesis of 1,2,3-triols.In this section,we systematically introduce the dihydroxylation of olefins and the synthetic methods of 1,2,3-triol compounds.The dihydroxylation reactions of olefins are mainly divided into syn-dihydroxylation and anti-dihydroxylation reaction.The traditional synthesis methods of 1,2,3-triols with three continuous stereocenters is mainly through diastereoselective addition of carbon-nucleophiles to the carbonyl moiety with two adjacent hydroxylated stereocenters or diastereoselective dihydroxylation of secondary allylic alcohols.Section II:Molybdenum-catalyzed diastereoselective anti-dihydroxylation of allylic alcohols.In this part,we developed the anti-dihydroxylation of secondary allylic alcohols by the Mo-BHA/hydrogen peroxide catalytic oxidation system.After screening various reaction parameters including Mo-catalysts,ligands,solvents and reaction temperature,the optimal conditions for the reaction were identified.It turned out that the molybdebum-bishydroxamic acid(Mo-BHA)catalytic system enables the highly diastereoselective dihydroxylation of E-disubstituted,terminal and trisubstituted alkenes,while the ligand-free conditions using molybdic acid as the catalyst allow the synthesis of 1,2,3-triols with the syn/syn-configuration in high diastereoselectivities.This reaction is bestowed with the following advantages:it is complementary to the classic osmium-catalyzed syn-dihydroxylation of olefins in terms of diastereoselectivity;a series of 1,2,3-triols with three continuous stereocenters were synthesized in high yield and high diastereoselectivity;this reaction is distinguished by a broad substrate scope,up to excellent diastereocontrol,high level of enantiospecificity and the use of environmentally benign hydrogen peroxide as the oxidant.The preliminary mechanistic investigations reveal that this anti-dihydroxylation consists of an initial epoxidation and the subsequent hydrolysis.Because of the high level of diastereo-and regiocontrol in the epoxidation and hydrolysis,respectively,the final triol products can be obtained in excellent diastereomeric ratios.