Research group of Liu Qiang, associate professor of Tsinghua University: Manganese catalyzed dideoxy coupling reaction of primary alcohol and aryl alcohol

Because of the characteristics of renewable, cheap and easy to get, the catalytic conversion of lead biomass resources has been widely concerned by scientists in recent years Alcohol molecule is one of the important platform compounds of biomass The development of deoxidization of alcohol molecule is an effective way to produce high energy density fuel and basic chemicals by using biomass resources The famous Barton McCombie and catalytic hydrogenolysis reactions can effectively realize the monodeoxygenation of alcohols It will be of great significance in biomass conversion if the dideoxy coupling reaction of two alcohols can be realized directly This reaction involves the simultaneous breaking of two inert C-O bonds, which is undoubtedly very challenging Recently, Liu Qiang, associate professor of Tsinghua University, reported a manganese catalyzed dideoxy coupling reaction between primary alcohol and aryl alcohol, through which alkene (alkane) compounds can be efficiently prepared Relevant results were published in Angew Chem Int Ed (DOI: 10.1002/anie.201809333) Introduction to the research group of Associate Professor Liu Qiang the research group of Associate Professor Liu Qiang now has 5 doctoral students, 1 postdoctoral student and 3 visiting students At present, the main research direction of the research group is the design and synthesis of cheap metal catalyst and its application in green synthesis, biomass conversion and high-efficiency energy conversion system Liu Qiang, associate professor, associate professor and doctoral supervisor, basic molecular center, Department of chemistry, Tsinghua University In 2007 and 2012, he received his bachelor's degree and doctor's degree from Wuhan University respectively; in 2012, he won Humboldt scholarship and began to work as a postdoctoral researcher in Leibniz catalysis Institute of Germany; in 2015, he was selected into the "youth thousand talents plan" of the central organization department and joined Tsinghua University to carry out independent research; in 2018 He was supported by the excellent youth fund of the National Natural Science Foundation of China At present, he has published 27 high-level academic papers (including 5 j.am Chem SOC., 10 angelw Chem Int ed and 2 nature Commun.) as the first author and corresponding author The published papers were cited more than 2200 times, h index = 23 Leading scientific research achievements: Manganese catalyzes the dideoxy coupling reaction of primary alcohol and aryl alcohol Alcohols can be obtained through biomass conversion, and are a kind of basic small energy molecules Liu Qiang, associate professor, reported the first case of condensation of ethanol to butanol catalyzed by cheap metal manganese (j.am.chem.soc 2017, 139, 11941) Butanol was obtained by 92% selectivity, and the highest catalyst conversion number (ton up to 110000) has been achieved so far The reaction went through the process of dehydrogenation of ethanol to acetaldehyde, aldol reaction of acetaldehyde under the action of alkali to crotonaldehyde, which was further hydrogenated to butanol If additional water molecules are introduced into the reaction, acetals will be formed by reaction with intermediate aldehydes, and then carboxylic acids will be formed by dehydrogenation of acetals Based on this, the author successfully realized the direct conversion of manganese catalyzed alcohol to carboxylic acid without the participation of oxidants (org Chem Fornt 2018, 5, 1248) In this study, when aryl ethanol was used as the reaction substrate, the by-product 1,3-diarylpropene was obtained in 10% yield instead of carboxylic acid This side reaction can realize the process of self coupling of two alcohols, which has important potential application value In addition, 1,3-diarylpropene is also an important intermediate in organic synthesis, which can be used to construct other functional molecules Through the systematic optimization of reaction solvent, alkali, different catalysts and other conditions, the yield of the reaction has been greatly improved, and the reaction has good substrate applicability and excellent functional group compatibility (Figure 1) Figure 1 Dideoxy self coupling reaction of aryl ethanol (source: angelw Chem Int ed.) in order to further expand the scope of application of the reaction, the author further studied the cross coupling reaction between aryl ethanol substrate 1 and ordinary primary alcohol 2 Through the equivalence control of the two reaction substrates, the reaction can also obtain the olefin product of cross deoxidization coupling in medium to good yield, although the direct coupling product is a mixture of olefin isomers, which can be converted into a single alkane product by catalytic hydrogenation of cheap metal Ni (Fig 2) Fig 2 The author speculates that the intermediate phenylacetaldehyde 5A produced by Mn catalytic 1 dehydrogenation undergoes alkali mediated condensation to obtain the final product 2A In order to verify this conjecture, a series of control experiments are carried out When 5A is directly used as reactant, the target product can only be obtained in 50% yield without catalyst, which is far lower than the yield of catalytic reaction, and only 50% yield can be obtained in addition of catalyst This shows that when 5A is directly used as the reactant, the catalyst can not promote the conversion of the subsequent steps of the reaction In addition, another possible intermediate, α, β unsaturated aldehyde 6a, was produced in the aldol reaction of 5A In the absence of Mn catalyst, the target product 2A can be obtained in 84% yield, indicating that 6a is the key intermediate of the reaction (Fig 3) Figure 3 Verification of the control experiment of reaction intermediates (source: angelw Chem Int ed.) then, the author deeply understood the reaction process through kinetic study In the reaction system with catalyst (FIG 4A), the product is slowly generated, and no intermediate 5A and 6A are detected in the whole GC process, indicating that catalytic dehydrogenation is the decisive step of this reaction Furthermore, the kinetic behavior of the reaction was studied in the system without catalyst In the kinetic study using 5A as the substrate, the solvent is p-xylene, when 0.5 equivalent alkali is used, the author found that the initial rate of the reaction is greatly increased, but the final yield can only be less than 40% (Fig 4D); when the amount of alkali is increased to 2 equivalent, the final yield of 50% can be obtained at a very fast initial rate (Fig 4C ）The results show that the increase of alkali concentration is beneficial to the increase of selectivity and yield When ethanol with better alkali solubility is used as solvent, the yield and rate of the reaction are very low in the presence of 0.5 equivalent alkali (Fig 4e); when the amount of alkali is increased to 2 equivalent, the yield, rate and selectivity of the reaction are greatly improved (Fig 4b) This shows that only when the concentration of alkali is much higher than that of phenylacetaldehyde, can the reaction obtain the target product with excellent selectivity In the catalytic reaction, the dehydrogenation of alcohol to aldehydes is a slow step, which can make the intermediate aldehydes release slowly, so as to ensure that the concentration of alkali is much higher than that of the intermediate aldehydes Figure 4 Kinetic study of the reaction (source: angelw Chem Int ed.) through GC analysis, the author found that only a very small amount of CO and CO2 gas was produced in this reaction, and one carbon atom reduced in the coupling process was in the form of sodium formate Furthermore, the author conducted a series of control experiments and found that the removal of sodium formate experienced the process of reaction intermediates α, β unsaturated aldehyde isomerization into β, γ unsaturated aldehyde and allyl anion intermediates (Fig 5) Fig 5 Control experiment to verify the experience of sodium formate removal (source: angelw Chem Int ed.) based on the control experiment and kinetic results, the author speculated the possible route of the catalytic reaction (Fig 6) Firstly, phenylethanol 1A catalyzes dehydrogenation to produce the intermediate phenylacetaldehyde 5a, which undergoes aldol reaction under the action of alkali to generate α, β unsaturated aldehyde 6a, 6a, and then isomerizes into β, γ unsaturated aldehyde 7a; it is attacked by hydrogen peroxide to remove a molecule of formic acid, and at the same time generates allyl anion 12a; 12a is finally protonated to generate the target product Figure 6 The possible reaction mechanism (source: angelw Chem Int ed.) was recently published on angelw Chem Int ed by Yujie Wang, Zhihui Shao, Kun Zhang and Qian Liu Wang Yujie, a doctoral student, and Shao Zhihui, a doctoral student, are working together The above research work was funded by NSFC and Guangdong Provincial Department of education Review of previous reports: research group of Liu Qiang, associate professor of Tsinghua University: regional selective olefin isomerization controlled by cobalt catalytic kinetics Today, science and technology elements are increasingly valued in economic life, China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.