S,O‐Ligand Promoted meta‐C−H Arylation of Anisole Derivatives via Palladium/Norbornene Catalysis

Abstract

Reversing the conventional site-selectivity of CÀ H activation processes provides new retrosynthetic disconnections to otherwise unreactive bonds. Here, we report a new catalytic system based on palladium/ norbornene and an S,O-ligand for the meta-CÀ H arylation of aryl ethers that significantly outperforms previously reported systems. We demonstrate the unique ability of this system to employ alkoxyarene substrates bearing electron donating and withdrawing substituents. Additionally, ortho-substituted aryl ethers are well tolerated, overcoming the "ortho constraint", which is the necessity to have a meta-substituent on the alkoxyarene to achieve high reaction efficiency, by enlisting novel norbornene mediators. Remarkably, for the first time the monoarylation of alkoxyarenes is achieved efficiently enabling the subsequent introduction of a second, different aryl coupling partner to rapidly furnish unsymmetrical terphenyls. Further insight into the reaction mechanism was achieved by isolation and characterization of some Pd-complexesbefore and after meta CÀ H activation-prior to evaluation of their respective catalytic activities.

Shapiro and Bamford-Stevens reactions – revisited

“…In 2016 Buchy et al investigated the Shapiro reaction with the use of the deuterated isopropylidene endgroup. Firstly, the two-step modification yielded (prop-1-en-2-yl-d5)lithium (35) from trisylhydrazone 34 upon treatment with the n-butyllithium and TMEDA. Trisyl hydrazone 34 was synthesized from deuterated acetone (33) and trisyl hydrazine.…”

“…In the second step, the desired product was obtained in 27% yield after reaction with MeLi. 35 Xu et al presented the visible-light-inducted annulation of phosphoryl diazomethylarenes and pyridinium 1,4-zwitterionic thiolates leading to the dicarboxylate derivatives. The diazophosphinates and diazophosphonates were synthesized from tosyl hydrazones 105a-p which reacted with sodium carbonate to yield the final products 106a-p in rather moderate yields.…”

Functionalized Cycloolefin Ligand as a Solution to Ortho-Constraint in the Catellani-Type Reaction

“…Moreover, Pd(II)-initiated Catellani-type reactions were developed as a new advance by the groups of Bach, 13 Yu, 5a Dong, 14 Zhou, 15 Zhang, 16 and Fernańdez-Ibańẽz. 17 In addition, a series of structurally modified NBEs (smNBEs) have been designed to finely tune the Catellani reaction in terms of chemo-, regio-, and enantioselectivities, as witnessed by the works of the Yu, 5b Dong, 18 and Zhou 19 groups. More recently, our group reported that the Catellani-type reaction can proceed without the participation of NBE by the development of an unstrained hybrid cycloolefin ligand, which extended the concept of Pd/ NBE catalysis to more general Pd/olefin catalysis.…”

“…18 A similar strategy was recently applied to Pd(II)-initiated mono meta-arylation of anisole derivatives by the Fernańdez-Ibańẽz group. 17 Despite these advances, the smNBE strategy for overcoming the orthoconstraint still suffered from some limitations, such as diminished catalytic activity and limited scope of the electrophile. 25 We noticed that, for another synthetically useful reaction category, the ortho-alkylative Catellani-type reaction, a general solution to ortho-constraint, remained elusive (Scheme 1d).…”

“…More types of electrophiles, including acyl and heteroatom-containing ones, have been introduced into this reaction by the groups of Dong, Gu, Luan, Liang, and others, which further improved the generality of this chemistry. Moreover, Pd­(II)-initiated Catellani-type reactions were developed as a new advance by the groups of Bach, Yu, Dong, Zhou, Zhang, and Fernández-Ibáñez . In addition, a series of structurally modified NBEs (smNBEs) have been designed to finely tune the Catellani reaction in terms of chemo-, regio-, and enantioselectivities, as witnessed by the works of the Yu, Dong, and Zhou groups.…”