Mechanistic Insights Into The Rh-Catalyzed Synthesis Of N-Heterocyclic Compounds With Cyclobutanol/Cyclopentanol-Substituted Aryl Azides And Ag(?) Catalyzed Hydroamination Of Alkynes

Nitrene has the characteristics of high reactivity and diverse reaction types.It is a very important organic active intermediate and plays a very important role in organic synthesis.Recently,transition-metal-catalyzed nitrene transfer reactions have attracted increasing research interests in organic synthesis to construct C-N bonds in a straightforward manner.The classical reactions of transition-metal-catalyzed nitrene transfer have aziridination and C-H amination.Moreover,the reactions also include difunctionalization of alkenes,cascade reactions,and cycloaddition reactions.Among nitrene transfer reactions,on the reaction of constructing C-N bonds with aryl azides reagent as nitrogen source,the ring expansion catalyzed by Rh2(?)have achieved very good results,but the detailed mechanism is not clear.The mechanism of Rh2(?)-catalyzed ring expansion of ortho-cyclobutanol-substituted aryl azides to access N-heterocycles was investigated by DFT calculations.And the origin of the different chemoselectivities for the ortho-cyclobutanol-substituted and ortho-cyclopentanol-substituted aryl azides was discussed.After the generation of the key Rh2(?)-N-arylnitrene intermediate A,computational results suggest that it is more feasible to undergo the proton transfer from the O-H group of ortho-cyclobutanol moiety to the nitrene site in singlet state,being along with the four-membered ring expansion via[1,2]migration in a concerted manner,to form the key intermediate B.Subsequently,the[1,3]carbonyl group migration step driven by rearomatization could follow to yield the final benzazepinone product.For the substrate,ortho-cyclopentanol-substituted aryl azide,the H-atom abstraction(HAA)from proximal sp3 C-H bond in triplet state is more favorable than the competitive HAA/proton transfer from O-H group after the formation of the rhodium N-aryl nitrene intermediate.Subsequently,the C-H bond amination product,indoline,couldbe obtained via a radical rebound step.Recently,transition metal catalyzed hydroamination of alkynes has attracted great attention.Comparing to other traditional protocols in constructing the carbon-nitrogen bonds,hydroamination offers several advantages in terms of its easy accessibility of raw material,atom-economy,simple operation,mild reaction conditions and efficiency.Large amounts of nitrogen compounds could be synthesized via hydroamination,which has important scientific significance and application value.Silver(I)-catalyzed intramolecular hydroamination of propargylic alcohols can yield N-cyclization products via 5-exo-N attack,and the reaction has high region-and chemo-selectvities.In principle,there are two nucleophilic attack reactivity sites on the triple bond,namely,that the ring formation reaction is the chemical selectivity question of the cyclization through the nitrogen or the oxygen attack of amide;On the other hand,there are two regional selective sites,which determine the intramolecular hydroamination forms an exo-or endo-cyclization product.With regard to the regio-and chemo-selectvities generated by the reaction remaining unclear,the further research is needed.Computational calculations are applied to study the mechanism and the orgins of the selectivies.The computational results suggest that the Ag—CH3CN catalyst model is more advantageous for the initial cyclization process.For the four nucleophilic attack possible pathways,the 5-exo N nucleophilic attack process is most favorable because of the nitrogen atom is more nucleophilic than the oxygen atom on the amide group,resulting in the preferential occurrence of 5-exo N nucleophilic attack.After silver acetate assisted in the extraction of hydrogen from the amide group nitrogen atom and the hydrogen atom are transferred to the alkenyl C2 position,and the catalyst is removed to produce the final product.