Aminohalogenation Of ?- Unsaturated Nitrostyrenes

Aminohalogenation of olefins has become an useful tool in organic synthesis to induce the nitrogen atom and halogen atom in one reaction. In early period research of the reaction was limited in some simple olefins with low yield and regio- and stereoselectivity.In recent years, methyl cinnamate and chalcone derivates have been reported as the alkenes substrates for aminohalogenation reaction, and resulting in high yields and excellent regio- and stereoselectivities. In our group's research, we reported some aminohalogenation reaction of a, ?-unsaturated nitriles, such as a, ?-unsaturated nitrostyrenes ?-methyl-?-nitrostyrenes, in good yield and stereoselectivity. To expends the usage of the aminohalogenation reaction, our research focus on the four points below:1. use ?-unsaturated nitrostyrenes as substrates, NBS/NCS as the halogen source,and BocNH2 which widely applied in organic synthesis as the nitrogen source, we firstly investigated many reactions to find the optimal reaction condition under which 13/20 substrates with different substituents had been tried to perform the aminohalogenating reactions. Good yields were obtained in all the reactions,indicating the wide application scope of the reaction condition. In addition, the Boc protective group of the products could be removed under mild reaction condition without strict water- and oxygen-free requirements, suggesting the practical values of the newly found reactions.2. ?-methyl-(3-nitrostyrenes was used in the reaction with BocNH2 .We changed the synthesis strategy in the reaction, used the BocNH2 and BocNBr2 in one- pot.Using the DCM as solvent, K3PO4 as catalyst, we got 15 products through the reaction with good yield (>75%) and stereoselectivity, the highest d.r. is 23:1.Append the catalyst is intoxicity and cheap, so it can be used in many organic synthesis effectually.3. We used ?-nitro-2-styrene, which was rarely used before, as the substrate of the aminohalogenating reactions. Considering the unique reaction feature of the substrate, we changed the synthesis strategy. We treated the substrate with BocNH2 and BocNBr2, and successfully finished the aminohalogenating reactions which could not take place at all when the substrate was treated with NBS and BocNH2.Furthermore we also tried to optimize the reaction condition. We had investigated the influence of the reactant-ratio, solvents and catalysts on the yield of the reactions. We found that the reaction could be completed in best yield and selectivity with DCM as solvent, K3PO4 as catalyst. This optimal reaction condition was extended to 15 different substrates among which the best value of d.r. (23:1) was achieved. The reaction is very convenient and efficient since the reaction condition is mild and the used catalyst is intoxicity, cheap and easy to be separated from the reaction system.And the Boc- protecting group can be moved easily.4. We chose the benzamide as the nitrogen source because it's very common.Using N,N-di-bromobenzamide as the halogen source with the benzamide as nitrogen source and K2CO3 (20%) and Ni(OAc)2 (1%) as catalysts, we found the reactions could be completed with good stereo selectivity and in good yield. Moreover, the reaction was also extended to 11 different substrates among which the best value of d.r. (8.2:1) was achieved.The structures of the products of the aminohalogenating reactions were confirmed by 1H-NMR, 13C-NMR and HR-MS. Four product was selected to form the single crystal and be analysised by x-ray diffraction. In summary, we have comprehensively studied the aminohalogenation of olefins, extended the substrates as well as the nitrogen source. We have determined optimal reaction conditions for 4 series of reactions which are all mild, convenient and efficient, showing good practical potential. With the new findings we have made, a deepening insight on the aminohalogenating reaction may be achieved.