Ruthenium(Ⅱ)-Catalyzed Regioselective C(7)-H Allenylation Of Indole Derivatives

The heteroaromatic scaffolds indole/indoline are prevalent among a plethora of natural products and bio-active molecules,and thus functionalization of an indole segment has come up as a comprehensively manifested research objective in the demesne of organic synthesis.While the selective functionalization for the benzenoid core,especially the C7-site,was less reported.Based on the successful development of transition-metal-catalyzed C-H functionalization and the latent capacity in simplifying the process of post-modification and synthesis of biologically active molecules,drug molecules,and natural products,it is significant to accomplish the selective functionalization of indole segments at the C7-site by transition-metal-catalyzed C-H activation strategy.Taking into account the increasing requirements of allene segments in medicinal and synthetic organic chemistry,a ruthenium(Ⅱ)-catalyzed regioselective ortho C-H allenylation of electron-rich aniline and phenol derivatives has been described.Along with the inherent para nucleophilicity has been overcome,an ortho C-H allenylation of electron-rich aniline and phenol derivatives with the guidance of a directing group has been achieved,and a series of ortho-allenylation products which have great potential for synthesis were obtained with high regioselectivity.This method has many advantages,such as high efficiency,mild conditions and wide functional group tolerance.More significantly,a tetrasubstituted allene with optical activity can be prepared with high enantiomeric excess via a highly efficient chirality transfer.In summary,with gradually emerging of advantages including strong reactivity,high stability and high regioselectivity,a Ru(Ⅱ)-catalyzed C-H editing has become one of the most potential mediums to access the C-H bonds across the remote,less activated benzenoid core(C4 to C7)of indoles.If it can be applied to drug design and synthesis,chemical synthesis of natural bio-active molecules,large-scale industrial production and optimization of synthesis process,it will play an important advantage in medicine,material chemistry and other fields.