南开大学研发联芳基化合物高效合成新方法
南开大学近日发布消息称，该校化学学院叶萌春教授团队日前实现了简单芳烃和广泛使用的芳基硼酸试剂的选择性偶联反应的突破，从而克服了传统联芳基化合物生产过程中反应利用率低、成本高、环境污染严重、反应产物不可控等问题，可以方便快捷地构建各类联芳基化合物。
联芳基化合物在医药、农药、染料、新材料等领域被广泛应用。长期以来，发展简便、高效的联芳基化合物合成方法一直是有机合成研究的热点问题。
传统的联芳基化合物的合成是通过两类预活化芳基底物(卤代芳烃和芳基金属试剂)直接偶联实现的，反应不仅需要原料的预活化额外步骤，而且偶联反应有较高的废物排放，导致反应原子利用率低，成本高和环境污染严重。简单芳烃原料价廉易得，且反应原子利用率高，环境污染少，通过简单芳烃碳氢键直接进行芳基化反应来构建联芳基化合物受到了日益广泛的重视。但芳烃中的碳氢键不仅相对惰性，难于直接反应，而且数量多，性质相近，如何实现其选择性偶联是当前阶段面临的关键难题。目前，各类芳基化反应已经被陆续发展，选择性控制方面也取得了一定的成果，但是依然存在两个尚无法逾越的挑战：一方面，选择性控制手段主要局限于底物控制或者试剂控制，大大限制了底物、试剂的选择以及产物结构的多样性，亟需发展基于催化剂控制的通用性方法;另一方面，低毒、易操作、种类多样且广泛使用的芳基硼酸试剂的选择性偶联一直难以实现。
受以往反应底物中一些酰胺官能团可以对反应选择性起到重要影响的启发，叶萌春团队大胆设想，能否将酰胺类结构作为配体引入到反应体系中，从而有效控制反应的选择性，实现催化剂控制的通用性偶联?通过广泛而深入的研究，团队最终发现包括N,N-二甲基乙酰胺在内的多种酰胺化合物均可以促进甲苯和芳基硼酸的高对位选择性芳基化反应，其中N,N-二甲基甲酰胺的控制效果最好。在最优反应条件下，甲苯与多种取代的芳基硼酸均能高效偶联生成联芳香化合物，且邻/间/对位选择性高达0.5/0.9/98.6，反应收率最高达到90%。除甲苯外，其他单取代芳烃，如乙苯、异丙苯、氟苯、氯苯等，以及二取代和多取代芳烃同样适用于该体系，得到对位选择性芳基化产物，显示了该方法的广泛实用性。
由于芳基硼酸试剂的稳定、易得和低毒，这种催化剂控制的选择性芳基化反应有望在医药、农药和材料领域得到重要的应用。
A NEW METHOD FOR EFFICIENT SYNTHESIS OF ARYL
COMPOUNDS IN NANKAI UNIVERSITY
YEMENGCHUN,A PROFESSOR OF CHEMISTRY AT NANKAI UNIVERSITY, HAS MADE A BREAKTHROUGH IN THE SELECTIVE COUPLING REACTION OF SIMPLE AROMATIC HYDROCARBONS WITH WIDELY USED ARY BORIC ACID REAGENT. IT CAN OVERCOME THE PROBLEM OF LOW REACTION UTILIZATION,HIGH COST, SERIOUS ENVIRONMENTAL POLLUTION AND NON-REACTION PRODUCTS IN THE PRODUCTION OF TRADITIONAL AROMATIC COMPOUNDS,IT CAN EASILY AND QUICKLY CONSTRUCT VARIOUS AROMATIC COMPOUNDS.
DIARYL COMPOUNDS ARE WIDELY USED IN MEDICINE, PESTICIDES, DYES, NEW MATERIALS AND OTHER FIELD.THE DEVELOPMENT OF SIMPLE AND EFFICIENT SYNTHESIS METHODS OF DIARYL COMPOUND IS ALWAYS A HOT TOPIC IN ORGANIC SYNTHESIS .
THE TRADITIONAL SYNTHESIS OF DIARYL COMPOUNDS IS REALIZED BY DIRECT COUPLING OF TWO TYPES OF PRE-ACTIVATED AROMATIC SUBSTRATES (HALOGENATED AROMATIC HYDROCARBONS AND AROMATIC METAL REAGENTS).THE REACTION NOT ONLY REQUIRE ADDITIONAL STEPS OF PRE-ACTIVATION OF RAW MATERIALS,BUT ALSO HIGH WASTE DISCHARGE,RESULTING IN LOW ATOMIC UTILIZATION,HIGH COST AND SERIOUS ENVIRONMENTAL POLLUTION.SIMPLE AROMATIC HYDROCARBON IS CHEAP AND EASY TO OBTAIN,AND THE RATE OF ATOMIC UTILIZATION IS HIGH AND LOW ENVIRONMENTAL POLLUTION. THE AROMATIZATION OF SIMPLE AROMATIC HYDROCARBONS THROUGH HYDROCARBON-HYDROGEN BONDS HAS BEEN MORE ATTENTION.HOWEVER, THE CARBON-HYDROGEN BONDS IN AROMATIC HYDROCARBON ARE NOT ONLY INERT AND DIFFICULT TO REACT DIRECTLY,BUT ALSO LARGE QUANTITY AND SIMILAR PROPERTY,HOW TO ACHIEVE THEIR SELECTIVE COUPLING IS A KEY PROBLEM CURRENTLY.AT PRESENT, VARIOUS AROMATIZATION REACTION HAVE BEEN DEVELOPED AND SOME ACHIEVEMENT HAS BEEN MADE IN SELECTIVE CONTROL. HOWEVER, THERE ARE STILL TWO INSURMOUNTABLE CHALLENGES: ONE IS SELECTIVE CONTROL METHODS ARE MAINLY LIMITED TO SUBSTRATE CONTROL OR REAGENT CONTROL WHICH GREATLY LIMITS THE CHOIES OF SUBSTRATES,REAGENT AND DIVERSITY OF PRODUCT STRUCTURE. IT’S URGENT TO DEVELOP A GENERAL METHOD BASED ON CATALYST CONTROL. THE OTHER IS SELECTIVE COUPLING OF ARYL BORIC ACID REAGENTS WITH LOW TOXICITY,EASY TO OPERATE,VARIOUS AND WIDELY USED IS STILL TO BE ACHIEVED.
INSPIRED BY THE FACT THAT SOME AMIDE FUNCTIONAL GROUPS IN PREVIOUS REACTION SUBSTRATES CAN PLAY AN IMPORTANT ROLE IN THE SELECTIVITY OF THE REACTION.THE TEAM OF YEMENGCHUN BOLDLY ENVISAGED WHETHER THE AMIDE STRUCTURE COULD BE INTROUDCED INTO REACTION SYSTEM AS A LIGAND TO EFFECTIVELY CONTROL THE REACTION AND ACHIEVE UNIVERSAL COUPLING OF CATALYST CONTROL.AFTER DEEPLY RESEARCH,THE TEAM EVENTUALLY FOUND THAT A VARIETY OF AMIDE COMPOUNDS,INCLUDING N,N-DIMETHYLACETAMIDE,COULD PROMOTE THE HIGHLY PARA-SELECTIVE ARYLATION OF TOLUENE WITH ARYL BORIC ACID,AMONG WHICH N, N-DIMETHYLACETAMIDE HAS THE BEST EFFECT.UNDER THE OPTIMAL REACTION CONDITIONS, TOLUENE AND VARIOUS SUBSTITUTED ARYL BORIC ACIDS CAN BE EFFICIENTLY COUPLED TO DIAROMATIC COMPOUNDS, AND THE O/M/P SELECTIVITY IS AS HIGH AS 0.5/0.9/98.6, AND THE REACTION YIELD IS UP TO 90%. IN ADDITION TO TOLUENE,OTHER MONOSUBSTITUTED AROMATIC HYDROCARBON SUCH AS ETHYLBENZENE,ISOPROPYL BENZENE, FLUOROBENZENE, CHLOROBENZENE,ETC.,AS WELL AS DISUBSTITUTED AND POLYSUBSTITUTED AROMATIC HYDROCARBON ARE ALSO SUITABLE FOR THE SYSTEM,AND PARA-SITE SELECTIVITY AROMATIZATION PRODUCTS ARE OBTAINED, WHICH SHOWS WIDELY APPLICATION OF THIS METHOD.
DUE TO THE STABILITY, AVAILABILITY AND LOW TOXICITY OF ARYL BORIC ACID REAGENT, THIS CATALYST-CONTROLLED SELECTIVE ARYLATION IS EXPECTED TO BE WIDELY USED IN MEDICINE,PESTICIDES AND MATERIALS.
