Ligand effect on direct arylation by CMD process

Abstract

The ligand effect of electron-poor phosphines in the concerted metalation-deprotonation (CMD) process for intramolecular direct arylation was experimentally and theoretically demonstrated. The ligand acceleration effect (LAE) for the intramolecular direct arylation of 1-bromo-2-(phenoxymethyl)benzene increased in the following order: P(BFPy)3 > P{3,5-(CF3)2-C6H3}3 > PCy3 > P(3,4,5-F3-C6H2)3 > P(4-F-C6H4)3 = PPh3 ≫ P(C6F5)3. The use of highly electron-poor P(BFPy)3 allowed the catalyst loading to be decreased up to 0.01 mol%. The LAE is roughly proportional to the electronic effect of the phosphine ligand. The LAE was not observed in the case of P(C6F5)3 because of its lack of coordination ability for Pd(OAc)2, as confirmed by 31P NMR spectroscopy. The donating PCy3 ligand showed a higher LAE than PPh3. The relative activation free energies (ΔG≠) of the CMD process calculated by the density functional theory (DFT) at the M06-2X/6-31G(d) level with LANL2DZ showed the same trend as the experimental results. The LAE in CMD was further evaluated by DFT calculations using two approaches: (1) fragment energy analysis and (2) evaluation of NBO deletion energy in transition states in CMD. The results of the first technique indicated that the conformational change in PCy3 results in increase of activation energy (ΔE≠) in compared with PAr3 systems. The use of the second technique clarified that the highly electron-poor P(BFPy)3 ligand stabilized the CAr→Pd interaction and the electron-donating PCy3 stabilized the O→H⋯CAr interaction in the transition state in CMD.