Memfanco group of Shanghai Institute of organic chemistry: CO catalyzed enantioselective and enantioselective hydroalkylation of cyclopropene based on alkenylboronic acid

Introduction recently, the memfanco group of Shanghai organic Research Institute has realized the corresponding selective hydroolefinization of 3,3-disubstituted cyclopropene catalyzed by cobalt diphosphonate ligands for the first time Relevant research results were published in angelw Chem Int ed (DOI: 10.1002 / ange 201904994) By this method, a series of optically pure vinyl cyclopropanes can be easily obtained by using the abundant cheap metal cobalt in the crust This type of molecular skeleton exists in many bioactive molecules and natural products, such as acrinathrin, simeprevir (treatment of hepatis C), etc based on this methodology, the author finally realized the total synthesis of retinol X receptor antagonist (AGN 194204) (Figure 1) Fig 1 Synthesis of compounds containing chiral diene structure by a new asymmetric catalytic method (source: org Lett.) brief introduction to mengfanke research team, mengfanke research team has been committed to organoboron chemistry catalyzed by metal in the first transition system This strategy can be used to design different types of cheap metal catalysts to catalyze the addition reaction of organoboron reagents and olefins, and construct chiral compounds with high regioselectivity and stereoselectivity (ACS catalyst 2017, 7, 5693 − 5698; org Lett 2017, 19, 6610-613; chem.sci 2018, 9, 4992 – 4998; asianj Org Chem 2018, 7, 103 – 106) Leading scientific research achievements: cobalt catalyzed non enantioselective and enantioselective hydroalkylation of cyclopropene based on alkenylboric acid vinyl cyclopropane, as a very important kind of synthons, has been widely used in many organic reactions, such as various rearrangement reactions, transition metal catalyzed polymer polymerization, etc In addition, such a chiral ternary ring structure with olefin functional group also exists in many bioactive molecules (such as acrinathrin insecticide) and natural products Therefore, it is very important to obtain the molecular skeleton of allylidene cyclopropane with high enantioselectivity and enantioselectivity Compared with the traditional asymmetric catalysis strategy, it is usually realized by adding metal carbene to diene or by coupling addition and cyclization reaction in series Other classical methods such as Simmons Smith reaction have developed more mature However, the common problem of the above methods is that special functional groups are often needed in the reactants, which limits the substrate applicability of such reactions to a large extent In contrast, if vinyl cyclopropane can be constructed by direct enantioselective hydroolefination of cyclopropene, it will not only have more advantages in the scope of substrate application, but also can be realized from cheaper and easier raw materials In fact, asymmetric catalytic functionalization of cyclopropene has been studied for a long time It has been reported that the hydroboration, hydroaromatization, hydroacylation and hydroallylation of cyclopropene catalyzed by metal RH, the carbozincification of cyclopropene catalyzed by Fe and PD, and the hydroammoniation catalyzed by lanthanide rare earth metals In contrast, the asymmetric hydroolefinization of cyclopropene has not been successfully realized The only case report is that in 2018, Professor Marek's research group of Israel University of technology used copper catalyst to complete the reaction in the presence of alkenyl aluminum reagent However, the substrate limit of the reaction is relatively large, and the selectivity control is relatively general In recent years, Meng Fanke's research group has been committed to developing an economic, cheap and universal cobalt catalytic methodology Considering that alkenylboric acid is an easy to prepare starting material, the author thinks whether the two can be combined to realize the selective hydroolefinization of cyclopropene The author thinks that there are two main challenges to realize the above strategies: first, the activity of alkenylboron reagent is much lower than that of alkenyl metal reagent; second, how to control the high selectivity of the reaction under high temperature In order to solve the above problems, the author first tried to use 3,3-disubstituted cyclopropene 1a and alkenylboronic acid 2A as template substrate for the reaction conditions (Table 1) It was found that although only electronic rich alkyl phosphine ligands 4G and 4H could promote the reaction, fortunately, the non enantioselectivity and enantioselectivity were well controlled A very interesting phenomenon is that the reaction efficiency can be significantly improved by standing for 1 hour after the reaction is put into operation and then heating the reaction The reason for this phenomenon is that there may be a heterogeneous catalysis mechanism in the reaction process, that is, the catalytic active species caused by cobalt salt and alkali solvent are likely to form on the surface of potassium carbonate, and then catalyze the whole reaction Table 1 Condition optimization (source: angelw Chem Int ed.) in the subsequent substrate applicability investigation (Fig 2 and Fig 3), the author found that it has a very wide range of applicability for a variety of derived cyclopropene type substrates or alkenylboric acid type substrates It is worth mentioning that for boric acid substrates such as 5u, 5V, 5W and 5x, high yield and selectivity can still be obtained in the reaction, which can not be obtained in the reported reaction, to a certain extent, it also reflects the advantages of the methodology developed by the author Fig 2 Cyclopropene substrate range (source: angelw Chem Int ed.) Fig 3 Alkenylboric acid substrate range (source: angelw Chem Int ed.) Finally, the author has carried out the derivatization and Preliminary Mechanism Study of the reaction product (Fig 4) Starting from cyclopropene 1c and alkenylboric acid 2c, the optically pure retinol x-receptor antagonist (agn194204) can be obtained by one-step reaction with medium yield and excellent selectivity Compared with the previous chiral resolution method, it has great advantages Figure 4 Preliminary mechanism of functionalization and application (source: angelw Chem Int ed.) It is shown that (Fig 5): first, the hydrogen protons of the hydrogenolysis reaction are likely to come from boric acid completely, rather than the proton source introduced from outside; second, the chiral carbon cobalt bond formed after reaction addition will not isomerize in the subsequent reaction, but maintain strict stereospecificity; third: the deuterium boric acid mixture of 2 equivalent 3:1 is put into the phase reaction, and 25% can be obtained The deuterium products show that the breaking of the hydrogen oxygen bond of boric acid is probably the decisive step of the reaction Figure 5 Preliminary mechanism study (source: angel Chem Int ed.) was recently published in angel Chem Int ed (angel Chem Int ed 2019, DOI: 10.1002/angle 201904994) The author of this paper is Haiyan Zhang, Wei Huang, Tongtong Wang and Fanke Meng The above work was supported by the State Key Laboratory of metal organic chemistry, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, the "hundred talents plan", the "National Youth thousand talents plan", the Grant No 17yf1424100, and the class B strategic leading science and technology project of Chinese Academy of Sciences Review of previous reports: Meng Fanke research group of Shanghai Institute of organic science and Hong Xin research group of Zhejiang University: asymmetric conjugation addition reaction of a new type of catalytic dienyl borate about people and scientific research 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.