Research On Remote Hydrodeuteration And Hydroarylation Based On Olefins

Olefin is a class of important chemical raw material that can be easily available.Many types of high value-added products can be obtained by functionalization of olefins.With the development of transition metal catalysis,remote functionalization of olefins has been developed,which can effectively construct remote C-X(X = C,Si,B,O,N)bonds.However,protocols for construction remote C(sp3)-D bonds of olefins have not been reported until recently.The Friedel-Crafts alkylation is mostly used in the hydroarylation of olefins,but there are still some problems to be resolved,such as harsh reaction conditions and complex reaction steps.(1).The remote transfer hydrodeuteration of unactivated olefins catalyzed by nickel has been developed.After some optimization experiments,the best result was achieved by adopting nickel complex Ni-4 as a precatalyst together with D2 O and pinacolborane(HBpin)as the deuterium and hydride sources,respectively.Through the synergistic combination of chain-walking strategy and transfer hydrodeuteration,46 amide α-monodeuterated products have been synthesized with high yield and high selectivity.Experimental results demonstrated the directing group plays the critical role in the olefin isomerization process.Density functional theory(DFT)calculations suggest that the [NiII]-H species rather than the [NiI]-H species are the active intermediates of the reaction during olefin insertion and isomerization.(2).The transition metal-free catalyzed,HFIP promoted olefin hydroarylation has been developed.The regio-and chemoselective construction of indole bearing an all-carbon center at the C3-position has been achieved through utilization of hexafluoroisopropanol(HFIP)as the protonation reagent and solvent.After some optimization experiments,the optimal reaction conditions were determined: Olefin as substrate,indole as aryl source,n Bu4 NOAc as catalyst,reacted at 90℃ in HFIP for 24 hours.33 olefin hydroarylation products have been synthesized with high yields.The reaction involves transition metal-free and utilizes a green solvent(HFIP)as the protonation reagent,making it environmentally friendly.In contrast to previous report,application of this protocol to the synthesis of drug((±)MCRA)was pursued with an improved yield.Catalytic kinetics and deuterium-labeling experiments suggest that the protonation of olefin to generate carbocation is reversible and the rate-determining step.