Science: Hartwig group achieves high-efficiency boration of alkane-level C-H bonds

Compared with the development of more mature C (sp2)-H key activation, the study of C(sp3)-H key selective elective elective reaction is still relatively lagging, most studies focus on the cepene, acrylic, three-level C(sp3)-H keyFor non-activated fatty hydrocarbons, the key of the first-stage C(sp3)-H key can be higher than the second-level C(sp3)-H key, which means that the reaction activity of the former is lower than that of the latter when there are no other miscellaneous atoms at the adjacent siteIn the design of non-activated fat hydrocarbon C (sp3)-H key of the metamorphic reaction, if the substrate is not modified other guiding groups, the first-level C(sp3)-H key activation is easily accompanied by the competitive reaction of the second-level C(sp3)-H keyrecently, Professor John FHartwig of the University of California, Berkeley, based on previous research, used fatty hydrocarbon substrates as a limiting reagent to achieve highly selective boration of the First Class C (sp3)-H bond with the help of the Ir catalysis systemThe reaction does not require the involvement of other guiding groups, and the key to its success lies in the significant increase in the rate of catalytic reaction saphylicosis (2-mphen) and the lower reaction activity of competitive boronization of cyclic octane compared to other inert solvents, which greatly facilitates the target boronization reactionThe work is published in the top academic journal, Scienceimage source: Reference s1,transition metal catalyst can not only reduce the activation energy of C-H key fracture, but also control the selectivity of reaction through specific spatial structuresFor the C(sp3)-H-bond bobobolization process, in 2000, Professor John Hartwig, who was also at Yale University in the United States, used Cp Rh as a catalyst to use (Bpin) 2 as a source of boronization, completing the boronization of the alkane-level C(sp3)-H keyHowever, the reaction needs to be performed at a high temperature of 150 degrees C, with a very large excess of the substrate or directly used as a solvent to ensure the concentration of its reaction, not only the poor atomic economy, but also limit the application of the substrateIn addition, the underlying structure of the investigation is mostly relatively simple, sensitive military mission in the reaction system is difficult to be compatibleThe selective boration of the-Rh catalytic alkane spline C (sp3)-H bond (Photo Source: Reference s.2)boration reaction to the transitionmetal catalytic fatty hydrocarbon C (sp3)-H bond developed since then, although the reaction conditions have improved, the problem of substrate dosage has not been effectively solved, limiting its expanded synthesis applicationTo this end, people by adjusting the structure of the ligand to further optimize the catalytic system, can effectively reduce the amount of substrate to about 5 equivalent (boronization reagent as a limitreade), one after another to achieve the c(sp3) - H bond boboization of the activation site, such as radon, cyclopropyl bit, partially modified guided group substrate can also be in the case of less smooth boration, some systems can also add other reaction activity as a solventHowever, these reactions apply only to highly active fatty hydrocarbons and remain ineffective for non-activated alkanesProfessor John Hartwig, studying the C(sp2)-H-cone-silaneation reaction of Ir catalytic aromatic hydrocarbons, found that different alternative base-modified filias were used as matching experiences to make significant differences in the reaction resultsFor example, the ligand silaneized used in the design of aromatic hydrocarbon C(sp2)-H bonds and alkane-level C(sp3)-H bond bobobolization reactions The effect of the reaction is not ideal, only the product of the trace, and the target product can be obtained with excellent yield and good selectivity when replaced with 2-methylfilay (2-mphen), 2,9-dmphen (2,9-dmphen)inspired by this,they further examined the involvement of the two ligands in the alkane C (sp3)-H bond boronization reaction, which was used as an Ir pre-catalyst (Mes) Ir (Bpin) 3, and B2pin2 as a boration source, when bu2O was used as a template substrate When using 2-mphen as a ligand to participate in the reaction starting rate is 2,9-dmphen or tmphen 40 times, and with THF as the template substrate, this value rises to 80 times, also proves that 2-mphen can more effectively promote catalytic boration reactionthe effect of different ligands on the C(sp3)-H bond boronization reaction rate (Image Source: Resources 1)however, at this time the reaction is still carried out without solvents, but a significant increase in the reaction rate after switching to other ligands means that the system adds an inert solvent, reduces the concentration of fatty hydrocarbon substrates, and the reaction can still be carried out at a considerable rateThey then used the substrate positive dixane as a limiting reagent, cyclooctane as a solvent, the system heated to 100 degrees C, the substrate level C (sp3)-H bond boronratio ratio of the solvent boronization of more than 60:1The cyclane is more susceptible to boration, which is more likely to occur in the cyclane mixed design experiment, which shows that cyclane is more suitable for use as a reaction solventin addition,, they found that HBin, a by-product produced by boration of positive dilane, inhibited the reaction, resulting in a lower yieldHowever, due to the low boiling point of HBin, the reaction is heated to 100 degrees C under the protection of nitrogen airflow, HBin can be volatile removal, at this time the positive dilane occurs a level C (sp3)-H bond single boronization ratio of 6:1, the yield of single boronization products can reach 65%The positive cyclocyclane only contains a set of first-level C(sp3)-H bonds, the participation in the reaction can selectively obtain a single borate product, the other secondary, tertiary C (sp3)-H bonds did not borate, reflecting that the reaction has a good regional selectivityAfterto obtain the optimized reaction conditions, the author further examined the application range of the substrate, selecting the application range of the substrate, the use of the object as a pre-catalyst, 2-mphen as a ligand, B2pin2 as a borated reagent, fat hydrocarbon substrate as a restricted reagentThe reaction has good officer group compatibility, and can highly selectively achieve the first-level C(sp3)-H bond boronizationWhen there is no first-stage C(sp3)-H key or its spatial bit resistance is too large in the substrate, the second-stage C(sp3)-H key reacts, at which point the beta-C(sp3)-H key of the heterotom is more prone to boration Some substrates containing multiple methylseth form polyboritization products, and boronization occurs at reaction sites with smaller bit resistance when there are significant spatial resistances or significant differences between different methyls The hetle structure containing N, O and other hybrid atoms in the substrate can also occur smoothly in the first-level C(sp3)-H bond boronization the scope of application of the substrate (photo source: source 1) alkyl borate in the field of organic synthesis has important applications, for this reason, they also take borated products 15 and 31 as examples, it is Suzuki-Miyaura coupling, halogenation, oxidation and other derivation, showing the practical value of boronization reaction the derivation of alkyl boric acid 15 (photo source: Resources 1) the derivation of alkyl boric acid 31 (Photo source: 1) previously, we also described the work of non-activated fatty hydrocarboncs C (sp3) -H keboboboization reported by Professor Nathan D Schley of Professor Vanderbilt University in the United States (see recommendation) They combined with (Mes) Ir (Bpin) 3 pre-catalysts, combined with a dixen-based aromatic methane ligand previously rarely used in catalytic reactions, and also achieved high-efficiency boration of the first-level C(sp3)-H bond at a low substrate concentration However, the reaction is still limited to borated reagent B2pin2, and the fat hydrocarbon substrate is added to 5 equivalent the work of professor Nathan D Schley's team (Photo: Resources, 5) Professor John Hartwig broke through this limitation by using the non-activated fatty hydrocarbon substrate as a limiting reagent for the first time to achieve a high-selective boration of the first-level C(sp3)-H key without the involvement of a guided group Professor Wallet Aggarwal of the University of Bristol in the UK gave the work a high rating, likening it to highly skilled surgery that precisely manipulates the activation of specific C-H keys However, the reaction uses non-polar positive octane as a solvent and does not effectively dissolve the most polar molecules Perhaps people still need to find a more suitable solvent to further improve the response Reference s Raphael Oeschger et al., (2020) Diverse functionalization of strong alkyl C-h bonds by undirected borylation Science, DOI: 10.1126/science.aba6146 Thermal, Catalytic, Regiospecific Functionalization of Alkanes Science, DOI: 10.1126/science.287.5460.1995 Chen Cheng et al., (2015) Iridium-Catalyzed Silylation of Aryl C-H Bonds J Am Chem Soc., DOI: 10.1021/ja511352u Iridium-Catalyzed Silylation of C-H Bonds in Unactivated Arenes: A Steric Encumbered Phenanthroline Ligand Salysis J Am Chem Soc., DOI: 10.1021/jac.9b01972 Margaret R Jones et al., (2020) Iridium-Catalyzed sp3 C-H Borylation in Hydrocarbon Solvent Enabled By 2, 2'-Dipyridylarylmethane Ligands J Am Chem Soc., DOI: 10.1021/jacs.0c00524 Retrieved May 22, 2020, from https://cen.acs.org/synthesis/c-h-activation/Ir-catalyst-attacks-strong-CH/98/i19 7' Scientists finally crack nature's most common sex bond Retrieved May 22, 2020, from https://