JACS: David sarlah, University of Illinois, Urbana Champaign, USA, has realized palladium catalyzed dearomatic cis-1,4-diaminolation

Dearying can directly transform the aromatic structural fragments into complex molecules with a wide range of potential applications At present, in addition to Birch reduction and oxidative dearomatization of phenol, the research in this field mainly focuses on transition metal mediated dearomatization and catalytic dearomatization of phenol and heterocycles However, there are few reports on the catalytic methods of dearying functionalization of non activated aromatics Recently, David sarlah's group of University of Illinois Urbana Champaign reported several methods of dearomatizing through the cycloaddition reaction of heteroatom small molecules (aromatics) and various aromatic compounds activated by visible light (Figure 1A ）Compared with the traditional method, this method shows high atomic economy, step and redox economy Cis-1,4-cyclohexanediamine is an important structural fragment (Figure 1b) widely existing in natural products and bioactive compounds However, the synthesis of cis-1,4-cyclohexanediamine derivatives is still difficult, and a more general and effective synthesis strategy needs to be developed Recently, David sarlah's research group reported on J am Chem SOC (DOI: 10.1021 / JACS 8b13030) a method for the construction of cis-1,4-cyclohexanediamine derivatives by the dearomatic 1,4-diaminolation of aromatics (Figure 1a) (photo source: J am Chem SOC.) the author's preliminary study started with PD catalysis of naphthalene (5), MTAD (1) and amines (Table 1) Through the optimization of catalyst, reaction solvent, temperature and time, the author finally determined the optimal reaction conditions for 20h at - 20 ℃ with PD (PPh3) 4 as catalyst, EtOAc as solvent (photo source: J am Chem SOC.) under the optimized reaction conditions, the author screened the application range of amines in the method with naphthalene (5) and benzene (6) (Table 2) In addition to methylbenzylamine, other noncyclic secondary amines are active nucleophiles In addition, cyclic secondary amines such as pyrrolidine, piperidine, morpholine and N-methylpiperazine can also be transformed In addition to naphthalene, benzene is also reactive and can react with representative acyclic and cyclic secondary amines to obtain the corresponding products Next, we used primary amine as the substrate to study the dearomatic CIS diaminolation (Table 2) It is found that PD 2 (DBA) 3 / dppf can improve the reaction efficiency of the substrate Therefore, when naphthalene (5) reacts with a series of aliphatic amines, such as linear propyl, amyl and benzylamine, branched isopropyl, cyclohexyl and tert butylamine, the expected product is obtained in good yield In addition, this kind of dearomatic bifunctional reaction conditions are mild, and it can withstand alkene, methylsilyl protected alcohols and ester groups The expansibility of the transformation was also tested by the dearomatic bifunctionalization of naphthalene and propylamine on a gram scale Benzene (6) can react with primary amine smoothly, but the yield is slightly lower than naphthalene (photo source: J am Chem SOC.) then, the author studied the application range of aromatics with propamine as the amine source (Table 3) Due to the lack of regioselectivity for asymmetric substrates, the reaction products are mixtures In addition, the polynuclear heterocyclic aromatic hydrocarbons are also suitable for dearomatic cis-1,4-diaminolation, and have more obvious selectivity The dearomatic cycloaddition of polynuclear aromatic hydrocarbons is highly selective, and only the end unsubstituted ring is functionalized (photo source: J am Chem SOC.) then, the enantioselective PD catalyzed dearomatic cis-1,4-diaminolation (Table 4) was studied It was found that PD 2 (DBA) 3 / (s, SP) - t-bu-phosferox has high enantioselectivity by screening chiral ligands, and the conversion of secondary and primary amines to amine naphthalene adducts (97:3-99:1er) was realized by using this condition (photo source: J am Chem SOC.) dearying can be used as an entry point for molecular diversification and structural modification of amines (Figure 2) For example, compound 7I can be converted to unsaturated amines 11 and 12, saturated amines 13, aminoketones 14, and different substituted diamines 15 (Figure 2a) In addition, memantine (16), a drug for the treatment of Alzheimer's disease, can react with naphthalene ring to produce 7R, which can be further converted into olefin 17, saturated ketone 18 and diaminodiol 19 with various structures This shows the ability of this method to introduce various functional groups (photo source: J am Chem SOC.) conclusion: David sarlah's research group reported the dearomatic cis-1,4-diamino method of inactive aromatics and amines In this method, PD catalyzed visible light mediated allylic substitution of aromatic paraaromatics with amine nucleophiles was used to obtain cis-1,4-selective products with unique structure The resulting unsaturated products can be used for various structural modifications, so that complex molecular structures can be quickly constructed.