Research group of Professor Lan Yu of Chongqing University: DFT to explore the mechanism of Bronsted base mediated boronization of propargyl alcohol

Introduction organoboron compounds have become one of the most common structural units in organic synthesis, because they can be further efficiently converted into complex and useful molecules, such as electronic materials and bioactive natural products In the past few decades, transition metal catalyzed boration of unsaturated compounds has been widely reported However, due to the high reaction cost, multi-step operation and other adverse factors, the application of this method is limited to a certain extent With the concept of "green chemistry" and "atomic economy" being put forward, the boration of unsaturated molecules without transition metals, such as Lewis base or Bronsted base, has become the focus of researchers Although chemists have made a lot of researches on the mechanism of such reactions, there are still many doubts about the mechanism Understanding the reaction mechanism of a given reaction at the molecular level can not only optimize the existing conditions, but also contribute to the development of new reactions Therefore, it is of great significance to explore the mechanism of transition metal free boronization of unsaturated compounds by DFT calculation Recently, Professor Lan Yu of Chongqing University used DFT calculation to study the boronization of propargyl alcohol mediated by Bronsted in detail, hoping that this work can provide some new guidance for the experiment Related results were published online in org Lett (DOI: 10.1021/acs.orglett.9b01180) Brief introduction to Professor Lan Yu, Professor of School of chemistry and chemical engineering, Chongqing University, doctoral supervisor, winner of National Natural Science Foundation outstanding youth fund, and now director of Chongqing Key Laboratory of theoretical and computational chemistry Professor Lan Yu has been engaged in theoretical computational organic chemistry, organometallic chemistry and other fields for many years The mechanism analysis method based on covalent bond and conversion synthesis unit is proposed, which is applied to a large number of transition metal catalysis and small molecule catalysis coupling reaction mechanism research, and a comprehensive and systematic new model of organic chemical reaction mechanism research is proposed In the past five years, 27 papers have been published in j.am Chem SOC., angelw Chem Int ed., NAT Commun As correspondents, 27 papers have been published In the past three years, many reviews have been published in acc chem Res., chem SOC Rev., coor Chem Rev And other journals as correspondents Recently, the author profile of Professor Lan Yu was published in the authorprofile of angelw Chem Int ed (angelw Chem Int ed 2018, 57, 11852) At present, more than 160 papers have been published in various academic journals, and the total number of citations has exceeded 4000 At present, 15 papers have been selected into ESI high cited papers Professor Lan Yu won the first prize of 2018 Chongqing Natural Science Award (the first adult), and won the "2016 youth Chemistry Award of China Chemical Society" Frontier research achievements: DFT to explore the mechanism of Bronsted base mediated boronization of propargylic alcohol organoboron compounds have become one of the most common structural units in organic synthesis, because they can be further and efficiently converted into complex and useful molecules, such as electronic materials and bioactive natural products As a member of the family of organoboron compounds, alkenylboron compounds have attracted much attention because they are often used as raw materials for polysubstituted alkenes and π - extended polyaromatics In the past few decades, transition metals (Ni, PD, Cu, CO) have attracted more and more attention Among these organic synthesis methods, stereoselectivity and regioselectivity can be well realized by adjusting the spatial and electronic effects However, transition metal catalyzed boration is limited due to its high cost and multi-step operation Recently, with the concept of "green chemistry" and "atomic economy" being put forward, the transition metal free boronization has attracted the attention of researchers, because it can synthesize highly functionalized vinyl boron compounds in an environmentally friendly way As shown in Figure 1, a series of Lewis bases, such as n Buli, PBU 3, (PHS) 2, PPH 3, etc., have been proved to be able to catalyze the boration of alkynes to form alkenylboron compounds Under the condition of no transition metal, Lewis base can be combined with a borane group to activate diboron reagent and produce corresponding Lewis acid base adduct In addition, Bronsted bases usually interact with methanol to activate dibromide compounds In this process, Bronsted base assisted the deproton of methanol and then interacted with diboron compounds such as pinacol borate to form methoxyborate [h-base] + [meo-b 2pin 2] -, thus increasing the nucleophilicity of another boron unit According to this idea, a series of organoboron compounds using methoxyborates as precursors of organoboron reagents have been widely reported Fig 1 Activation mode of Lewis base / Bronsted base for dibromon reagent (source: org Lett.) in 2018, the author reported a Bronsted base mediated boronization of propargyl alcohol, which has good functional group and substrate compatibility (Fig 2) However, the mechanism of the reaction is not clear, such as (a) the way of boronization of propargyl alcohol; (b) how to alcoholize; (c) how to realize the second expansion and (d) how to reduce the dehydrogenation Understanding the reaction mechanism at the molecular level can not only optimize the experimental conditions, but also guide the development of new reactions The mechanism of this reaction is very important to understand the boration of unsaturated compounds mediated by Bronsted base Therefore, the detailed mechanism of the reaction was studied by DFT calculation Fig 2 Bronsted base mediated boronization of propargyl alcohol (source: org Lett.) based on the previous experimental study of the author, the author believes that the alkenylborate intermediate G is the key intermediate of the whole reaction Therefore, the reaction path is divided into two parts: boronization and reduction dehydrogenation (the mechanism is shown in Figure 3) Four possible boronizing pathways were explored Alkoxy exchange between a and propargyl alcohol reactant 1 forms propargyl borate B Then, boranyl nucleophilic attack C ≡ C bond to form boranyl vinyl anion C In path I (black line), methanol protonated anion C, followed by methoxyl exchange to produce borate E Next, borane group is substituted to form quaternary ring intermediate F, which can be further protonated to obtain alkenylborate intermediate G In path II (green line), methoxy is exchanged, and then intramolecular boron substitution provides intermediates h and I In route III (red line), intermediate C and methanol decompose to form intermediate J, which can be further protonated to provide species G in route IV (purple line), intermediate J can also be produced by C ≡ C in intermolecular nucleophilic attack reactant 1 of methoxyborate a Starting from the intermediate g of alkenylborate, three possible reductive dehydrogenation paths have been explored In route V (black line), alkoxy exchange between methoxyborate A and alkenylborate g forms anion intermediate K In the intermediate, the α, β - unsaturated ketone can be activated by boralkyl group Therefore, the intramolecular nucleophilic attack of boranyl group can provide the intermediate L After B-O elimination, a new five membered ring C = C double bond intermediate m was obtained Finally, vinyl boron product 2 can be produced by protonation In route VI (red line), methoxyborate a directly attacks intermediate g to produce intermediate n Then B-O was eliminated to obtain vinyl borate M In route VII (green), alkenylborate intermediate G is directly b-o-bonded to eliminate the production of diene intermediate o Then, methoxyborate A is nucleophilic to attack diene to produce M Fig 3 Bronsted base mediated boronization mechanism of propargyl alcohol (source: org Lett.) M11 / 6-311 + G (d) is used in this calculation, p) / / B3LYP / 6-31 + G (d) method, the calculation results show that the optimal path for boronization to form alkenylborate intermediate G is path I, namely alkoxy exchange between propargyl alcohol and methoxyborate a to form alkynyloxyborate intermediate B, then intramolecular nucleophilic attack C ≡ C bond to form boranyvinyl anion C, then methanol protonation anion intermediate C And methoxy exchange to produce borate intermediate E Then, borane group is substituted to form quaternary ring intermediate F, which can be further protonated to obtain alkenylborate intermediate G In the path of reduction and dehydrogenation, the optimal path is V, that is, the second alkoxy exchange once again introduces the diboron group into the molecule The next intramolecular nucleophilic attack provides the spiro intermediate L Finally, β - methoxy elimination and protonation produce the final boronization product (see article doi: 10.1021/acs.orglett.9b01180 for detailed calculation process) The first authors of this paper are Chen Deluxe, a postgraduate of Chongqing University, Professor Lan Yu and Dr Bai ruopung of Chongqing University, and Professor Song Qiuling of overseas Chinese University The research work was supported by National Natural Science Foundation of China (21822303, 21772020), basic scientific research fund of Central University (2018cdxz002, 2018cdptcg0001 / 4) and postdoctoral research fund of Chongqing University (xmt2018085) Nowadays, people and scientific research have been paid more and more attention in the 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.