Catalytic Oxidation Of Mn-PYBP To Synthesize Chiral Amino Alcohols

Chiral amino alcohol compounds are very important compounds,which are not only widely present in natural products and drug molecules,but also often used as chiral ligands or chiral assistants for many catalytic reactions.There are several common methods for the synthesis of chiral amino alcohols,such as:C-H bond amination reaction;hydroamination reaction of hydroxyl-containing olefin;reduction reaction of hydroxyl-containing imine;reduction reaction of aminoketone;Mannich reaction;hydroxyl amination of olefin and ring-opening reaction of epoxy,etc.These methods have their own advantages and disadvantages,and some progress has been made.Since C-H bonds are the most common chemical bonds in organic moleculars,it is more convenient and efficient to synthesize useful moleculars via the direct functionalization of C-H bonds is favored by scientific researchers.C（sp3）-H bond oxidative asymmetric hydroxylation reaction is an important challenge for the synthesis of chiral alcohols.However,chiral alcohol to achiral ketone is hardly be avioded,which becomes is a key for this chemical process.As far as our knowledge,the examples for highly enantioselective oxidation of C-H are rare and the enantioselectivities are no more than90%.Due to the high specificity and reactivity,enzymes often exhibit extremely high specificity and reactivity when catalyzing such reactions.The metal catalysts currently used in this field are mostly enzyme derivatives such as metalloporphyrin catalysts derived from heme and metal aminopyridine catalysts derived from non-heme.At present,the main methods adopted to solve the problem of excessive oxidation are using polar solvents to passivate the reaction activity of the product alcohol or using the interaction between the catalyst and the substrate to stabilize the product alcohol,etc.,and certain results have been achieved.If the oxidative hydroxylation of the substrate containing amine groups can be carried out to obtain enantioselective hydroxyl products,then chiral amino alcohols can be obtained.At present,such work has not been reported.Therefore,we decided to use the aminopyridine manganese complex developed by our research group as a catalyst,hydrogen peroxide as an oxidant,and 2-phenylethylisoindoline-1,3-dione and its derivatives,some interesting nitrogen-containing compounds in a fluorine-containing solvent.The benzylic hydroxylation of These compounds has been studied.By screening oxidants,catalysts,reaction solvents,additives and reaction temperature and other conditions,the optimal conditions for the reaction were finally determined,and the range of substrates was expanded.The substrate range of the reaction is relatively wide,the yield is between 40%-60%,and the enantioselectivity of the reaction is very excellent,up to 98%.It is worth mentioning that when we perform oxidation reactions on some optically pure substrates that contain chiral sites,the catalyst and the substrate’s own chirality have an obvious matching effect.This phenomenon is more detailed in the article.discussion.We also conducted isotopic oxygen atom tracing experiments to study the reaction mechanism.In this paper,a series of chiral amino alcohols were synthesized by catalytic oxidation using protected amine compounds as substrates and manganese aminopyridine complexes as catalysts.The catalytic system has simple operation and mild conditions,and provides an efficient,green,simple and feasible method for the synthesis of chiral amino alcohol compounds.