Palladium(ii)-catalyzed coupling reactions with a chelating vinyl ether and arylboronic acids: a new Heck/Suzuki domino diarylation reaction

Abstract

A mild and novel palladium(II)-catalyzed domino Heck/Suzuki alpha,beta-diarylation-reduction of a dimethylaminoethyl substituted chelating vinyl ether was developed by using electron-rich arylboronic acids in combination with p-benzoquinone. Based on the preparative results, a catalytic cycle is proposed. Further, highly regioselective palladium(II)-catalyzed alpha- or beta-monoarylation of the chelating vinyl ether was achieved using either a bidentate ligand or by employing ligand-less conditions.

Transmetallation Versus β‐Hydride Elimination: The Role of 1,4‐Benzoquinone in Chelation‐Controlled Arylation Reactions with Arylboronic Acids

“…This suggests that performing the reaction in DMF strongly hampers the production of 4 in favour of 3 , regardless of the addition of BQ to the reaction mixture. This is in line with the experimental results that showed that polar solvents increased the production of 3 6, 7. However, an energy difference of 13 kJ mol −1 should result in the almost complete selectivity of 3 , which indicates an overestimation of the calculated difference in free energy.…”

“…The transition state (TS) for internal phenylation ( TS-a ) was found to be 25 kJ mol −1 higher in energy than the TS for terminal phenylation ( TS-b ). The free-energy profile is presented in Figure 1 and is in agreement with the experimental outcome of the reaction when the oxidative Heck product is formed, given that when chelation from the alkene is feasible, that is, no strongly coordinating bidentate ligand is present in the reaction mixture, the terminal product is formed with a 3 / 2 selectivity of >50:1 6. This is equivalent to the selectivity obtained with the Pd 0 -catalysed Mizoroki–Heck reaction 5a, 11.…”

“…Potential bridged dimers of the complexes were excluded from the computational study. The computationally simple Pd(OAc) 2 was used in the calculations and this is an experimentally functional Pd II source, although the preparative optimisation revealed trifluoroacetate as the optimal Pd II source 6, 7. Unless otherwise stated the B3LYP-D3 free energies presented herein are given relative to Pd(OAc) 2 associated to 1 (complex I , Figure 1) because this complex was considered to be a suitable starting point for the reaction.…”

“…Notably, a comparison of the lowest free-energy barriers to β-hydride elimination ( TS-e ) and transmetallation without BQ association ( TS-h ) showed that the latter was calculated to be preferred by 10 kJ mol −1 . However, these values were calculated by using settings that reflect the optimised reaction conditions leading to 4 , and not the oxidative Heck product 3 , for which DMF has been used as solvent in the experimental protocol 6. Intriguingly, by changing the parameters to be suitable for DMF instead of dioxane in the solvent model the preferred reaction pathway was indeed calculated to be the β-hydride elimination ( TS-e ), which was 17 kJ mol −1 less than the energy of the competing transmetallation pathway when BQ was absent ( TS-h ).…”

Development of Stereocontrolled Palladium(II)‐Catalyzed Domino Heck/Suzuki β,α‐Diarylation Reactions with Chelating Vinyl Ethers and Arylboronic Acids

“…Previously, our research group reported a novel palladium(II)-catalyzed domino Heck/Suzuki β,α-diarylation of an achiral dimethylaminoethyl-substituted vinyl ether using an excess of arylboronic acid in combination with p -BQ 10c. For the domino Heck/Suzuki reaction, we proposed a mechanism involving a chelation-controlled carbopalladation step,11 which was supported by recent density functional theory (DFT) calculations, highlighting the crucial role of p -BQ in the catalytic process 12.…”