Manganese-Catalyzed Vicinal Trifluoromethylazidation Of Alkenes

As a strong electron-withdrawing group,trifluoromethyl can significantly modulate the physical,chemical and biological properties of the drugs,promote to be the absorbed better,and metabolization of drugs in time.On the other hand,azide group as an important biologically active functional group is also widely found in drug molecules.In addition,organic azides are also important organic synthesis intermediates for the synthesis of valuable compounds such as amines,tetrazoles and triazoles.Therefore,it is particularly important to simultaneously introduce both trifluoromethyl and azide groups into alkene derivatives.However,the pre-existing methods suffer from the disadvantages of requiring expensive catalysts,and expensive and dangerous reagents.Therefore,it is of usefulness to develop protocols simultaneously introduce both trifluoromethyl and azide groups into alkenes with low cost catalyst and safe reagents under mild conditions.Herein,a protocol was developed to realize the simultaneous introduction of both trifluoromethyl and azide groups into alkenes with low cost manganese salts as catalyst,cheap and stable CF3 SOONa as trifluoromethyl source,stable and readily available TMSN3 as the azide reagent,and TBHP as oxidant.Various β-trifluoromethyl substituted alkyl azides were directly synthesized from allylbenzene,styrene,1-allylnaphthalene,benzyl methacrylate,aryl long chain alkenes,long chain aliphatic alkenes,ether alkenes,amine alkenes,branched alkenes and cyclic alkenes under simple and mild conditions with isolated yield of 34-86%,indicating good functional group tolerance and broad substrate scope of this protocol.The mechanism study indicated that the reaction was initiated by a trifluoromethyl radical.For confirming the utility of this protocol,additional experiments were carried out to transform some of the obtained β-trifluoromethyl substituted alkyl azides to the corresponding CF3-substituted amines,tetrazoles and triazoles via Staudinger reduction,[2+3] cyclization reaction and Huisgen reaction.