Boron chemistry angelw: cupric catalyzed triborization of Alkynes

There is no doubt that organoboron compound is an important and useful intermediate in organic synthesis Because of its advantages of easy preparation, it has been widely used in synthetic chemistry, drug molecular preparation and material chemistry Among them, polysubstituted boron compounds can be used as bioactive molecules or practical synthetic blocks, and play an important role in modern organic Monosubstituted and disubstituted organoboron compounds have been widely used, but the research of 1,1,1-trisubstituted organoboron compounds is relatively less, but this kind of compound is also an intermediate worthy of study, so it is worth developing effective synthesis methods The researchers have made some progress in the triborization reaction Matteson group has developed the low-temperature boronization of chloroform, but it needs six times the amount of lithium metal Mita, Sato and others have realized IR catalyzed 2-ethylpyridine triborization, but it is only suitable for electron rich substituted pyridine ring, and the substrate range is narrow Chirik's group reported that the synthesis of benzyl tribasic borate by Ni catalysis was highly selective and yield, but the range of substrate was still limited Huang group prepared 1,1,1-tribromoalkanes by CO catalyzed two-step dehydroborization-hydroboration, but the substrate was limited to activated alkenes Alkyne is a common precursor reagent for the synthesis of organic boron In 1995, the research group of Marder reported the 1,1-diborization reaction of Styrene Catalyzed by RH, and prepared the corresponding 1,1,1-triphosphate esters (scheme 1a) In 2017, chirik team synthesized similar compounds (scheme 1b) by CO catalyzed 1,1-diborization of terminal alkynes Although these methods are useful, they all have some problems, such as poor functional group tolerance, expensive catalyst and many steps Recently, T b Marder group of University of welzburg, Germany, reported a method for the synthesis of 1,1,1-tribasic acid esters directly from cheap alkynes This method has high atomic efficiency and mild condition (scheme 1c) The related research results were published on angew.chem Int ed (DOI: 10.1002/anie.201909376) (source: angelw Chem Int ed.) the author optimized the conditions of phenylacetylene (1a) as the template substrate Through the optimization of the reaction conditions such as the type, dosage and temperature of copper salt, ligand and alkali, it was confirmed that the optimal conditions of the reaction were: 10 mol% Cu (OAC) 2 as the catalyst, 20 mol% n-butyl phosphine as the ligand, 1 equivalent KF as the base, substrate 40% in toluene The target product was obtained in 97% yield after 24 h reaction at ℃ (source: angelw Chem Int ed.) determined the optimal reaction conditions, and then the author expanded the reaction substrate (Table 2) Among them, the electrical effect has no great influence on the reaction Aromatic alkynes with electron donor or electron acceptor can participate in the reaction well, and the target product can be obtained in medium to good yield Many functional groups, such as alkyl group, methoxy group, dimethylamino group, halogen group, trifluoromethyl group, cyano group and ester group, are compatible with reaction conditions It is worth mentioning that the substrate with halogen does not produce the product of halogen boration, which provides conditions for further functionalization Subsequently, the heterocyclic and polycyclic arene substrates were tried, and the products were obtained in medium yield Finally, the reaction was amplified (5 mmol) and the final product was obtained in 87% yield (source: angelw Chem Int ed.) later, the author discussed the substrate range of alkynes (Table 3) For the 1,3-alkyne substrate, the author did not find the product of alkene boration, indicating that the reaction has high chemical selectivity (source: angelw Chem Int ed.) next, the author studied the reaction mechanism, caught the intermediate of alkynyl boron and 1,1-diborone in the experiment, and proposed the catalytic cycle process First, Cu (OAC) 2 is reduced to produce cuh intermediate; then, cuh is added to alkyne substrate to produce alkenylketone intermediate a, and a and hbpin undergo σ bond decomposition to produce alkenylborate ester 4; finally, 4 is again inserted into cuh, and σ bond decomposition to produce products and regenerate cuh catalyst to complete catalytic cycle (source: angelw Chem Int ed.) finally, in order to illustrate the practicability of the reaction, the author carried out the subsequent deboranylation of the reaction products, which provided an effective and direct method for the synthesis of α - alkenylborate ester and cyclic borate ester Summary: T b Marder group has developed a method of triborization of alkynes catalyzed by copper This method has high atom utilization, wide substrate applicability and is easy to enlarge The product was transformed in later stage, which provided a wide and practical method for the synthesis of organoboron compounds.