Professor Zhu Shifa research group of South China University of Technology: catalyst controlled high chemical and stereoselective donor / donor carbene transfer reaction

The author of the paper: Professor Zhu Shifa's research group hydrocarbon insertion and cyclopropane reactions are the most representative and common reactions in metal carbene chemistry, which are widely used in synthetic chemistry and pharmaceutical chemistry However, for allylic substrates, there are often competitive reactions between hydrocarbon insertion and cyclopropanation Therefore, it is of great significance to develop a highly efficient catalytic system which can obtain two products with high chemical selectivity from the same substrate Recently, Professor Zhu Shifa's research group of South China University of technology has realized the intramolecular hydrocarbon insertion and cyclopropanization of allyl donor / donor carbene with high chemical selectivity and high stereoselectivity based on the chiral catalytic system composed of chiral rhodium carboxylate dimer and divalent ruthenium and pyridine oxazoline Diazo compounds are important carbene precursors, but their explosive and dimerization characteristics seriously limit their application in carbene chemistry, especially in the production of donor carbene and donor / donor carbene How to control donor carbene and donor / donor carbene intermediates has always been a big problem for organic chemists In 2016, Professor Zhu Shifa of South China University of technology and Associate Professor Zhang Li of Sun Yat sen University collaborated to produce donor - and donor / donor carbene and intramolecular asymmetric hydrocarbon insertion reaction (angel Chem Int ed 2016, 55, 8452-8456) for the first time by using alkynone as carbene precursor and rhodium dimer as catalyst (source: angelw Chem Int ed 2016, 55, 8452-8456) on the basis of previous work, recently, Professor Zhu Shifa's research group successfully realized the catalyst controlled intramolecular allyl C-H insertion and cyclopropanation of donor / donor carbene with high chemical selectivity and stereoselectivity by using allylic substituted alkyne ketone as the substrate (source: angelw Chem Int ed.) firstly, allylacetamide alkyne ketone 1A was selected as the template substrate, and cyclopropanization was carried out under the catalysis of different chiral rhodium dimers to obtain product 2A After changing the catalytic system, it was found that in the catalytic system composed of ruthenium diiodide and ligand L6, a highly selective hydrocarbon insertion reaction could take place to obtain product 3a Furthermore, the optimum catalytic conditions for hydrocarbon insertion reaction were determined by fine tuning the Ru / L6 catalytic system [a] The reaction was performed in DCE under N 2 , 1a =0.2 mmol, [ 1a ]=0.1 M,   the yields andthe ration of 2a / 3a were determined by 1 HNMR [b] Rh 2 (II)=1 mol %, 25 °C [c] isolated yield [d] [Ru( p -cymene)X 2 ] 2 =5mol %, L =10 mol%, 80 °C [e] [Ru]=5 mol%, L =5 mol%, 80 °C [f][ 1a ]=0.025 M [g] [ 1a ]=0.025 M,[Ru( p -cymene)X 2] 2 = 5 mol%, l = 15 mol%, 80 ° C Table 1 After determining the optimal conditions for hydrocarbon insertion and cyclopropanization (source: angel Chem Int ed.), the author first carried out the substrate Adaptability Study on the Ru / L6 catalytic system for allylidene alkyne hydrocarbon insertion reaction When there are alkyl substituents on allyl double bonds, the chemical selectivity of the reaction is not affected, and the non enantioselectivity is more than 99:1, and the enantioselectivity is ≥ 96% ee, but the steric resistance of allyl 2-substituents will lead to a slight decrease in yield (3A-3D) When allyl 2-substituent is ester group, the enantioselectivity of the product decreases sharply (3f) Then, the 1,3-dicarbonyl substrate on alkyne ketone and the substituents at different positions on aniline aromatic ring were also investigated The results showed that the change of substituents on benzene ring had no effect on the selectivity of the reaction, and the reaction yield was moderate to good (3g-3o) [a] Reactionconditions: 1 =0 2 mmol , [ 1 ]=0.025 M, isolatedyield, DR was determined by 1H NMR spectrum of the crude reaction mixture Table 2 Allylhydrocarbon insertion (source: angelw Chem Int ed.) the author also investigated the cyclopropanation reaction of rhodium carboxylate as a catalytic substrate The target products were obtained quantitatively and the enantioselectivity was > 99:1 When the allyl 2-substituent is hydrogen atom, the enantioselectivity of the product ≥ 90% ee, and when the 2-substituent is non hydrogen atom (such as bromine atom), the enantioselectivity of the product drops sharply [a] Reactionconditions: 1 =0.2 mmol, [ 1 ]=0.1 M, isolated yield, DR was determinedby 1H NMR spectrum of the crude reaction mixture [b] 0 ° C Table 3 Allylic cyclopropanization (source: angelw Chem Int ed.) for Ru / L6 catalyst system, it can produce hydrocarbon insertion reaction with high chemical selectivity, which is mainly due to the presence of alkenyl of allylic substrate and terminal aryl of ligand L6 π - π interaction, which makes the carbon carbon double bond of allylic group be pulled away from the carbene center, and the hydrocarbon bond of allylic group is exposed to the carbene center, so the hydrocarbon insertion reaction takes place preferentially Figure 1 Ru / L6 catalytic system for selective hydrocarbon insertion (source: angelw Chem Int ed.) in addition to the study of chemical selectivity and stereoselectivity of cyclopropanization / hydrocarbon insertion of allylic substrate, based on the excellent chiral induction effect of Ru / L6 catalytic system, the author also inserts intramolecular hydrocarbon of alkylamide The investigation was carried out When the reaction temperature is 120 ℃, the target hydrocarbon insertion products can be obtained in medium to good yields, and have excellent enantioselectivity (5a - 5d) In addition, the reaction has good functional group tolerance, such as alkenyl (5e), methoxy (5g), and even bromine (5H) have no effect on the reaction results When different 1,3-dicarbonyl substituted alkyne ketone substrates and different substituted anilinone alkyne ketone substrates are used, the reaction can also proceed smoothly (5i-5m) Under the same reaction conditions, the intramolecular hydrocarbon insertion of benzyl group can also occur smoothly, and the reaction yield and EE value are significantly better than those of alkyl group (5N - 5S) [a] Reaction conditions: 1 =0 2 mmol , [ 1 ]=0.1 M, isolated yield, DR was determined by 1H NMR spectrum of the crude reaction mixture [b] 80 ° C Table 4 Hydrocarbon insertion of alkyl substituted alkyne ketone (source: angelw Chem Int ed.) Summary: Professor Zhu Shifa's research group has developed a catalyst controlled synthesis methodology, which realizes the allyl group with high chemical selectivity and stereoselectivity Intramolecular hydrocarbon insertion and cyclopropane reaction of donor / donor carbene The reaction has high efficiency, high selectivity and extensive substrate applicability, and can be realized by one pot method, and the substrate does not need to be added slowly This selective carbene transfer reaction controlled by catalyst ligands is not only helpful for people to better understand the reaction properties of metal carbene, but also is expected to provide useful reference for catalyst design This work was published on angelw.chem Int ed (DOI: 10.1002 / anie 201805676) The first author of this paper is Zhu Dong, a doctoral student Review of previous reports of the research group: Professor Zhu Shifa of South China University of technology research group: transition metal catalyzed efficient conversion of Alkynes